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Auto-Brewery Syndrome Explained: New Patient Cohort Identifies Culprit Bacteria, Fermentation
WASHINGTON — When a published case of auto-brewery syndrome (ABS) in China — caused by Klebsiella pneumoniae — received widespread publicity in 2019, patients reacted, sending emails to lead author Jing Yuan, in Beijing, China. Many of these inquiries were from patients in the United States who believed they might have ABS.
“Can you check to see if I have ABS?” patients asked Yuan.
For help, Yuan contacted Bernd Schnabl, MD, AGAF, at the University of California, San Diego, whose research was addressing alcohol-associated liver disease and who was also interested in the gut-liver axis and the role of gut microbiome–derived ethanol in metabolic dysfunction–associated steatotic liver disease (MASLD).
“She asked me, ‘Are you interested in looking into ABS?” Schnabl recalled at the Gut Microbiota for Health (GMFH) World Summit 2025. He dug in and formed what may be the largest research cohort thus far of patients with ABS — a group of 22 patients with their diagnosis confirmed through observed glucose challenge.
His soon-to-be-published
ABS is considered a rare condition, but “I’d argue that it’s rarely diagnosed because many physicians don’t know of the diagnosis, and many are actually very skeptical about the disease,” Schnabl said at the meeting, convened by AGA and the European Society of Neurogastroenterology and Motility.
Patients experience symptoms of intoxication when ethanol produced by dysregulated gut microbiota exceeds the capacity of the liver to metabolize it and accumulates in the blood, he explained.
“Patients constantly talk about brain fog; they can’t concentrate, and it can be very severe,” he said. “They don’t get a firm diagnosis and go from one medical center to another, and they also suffer from complications of alcohol use disorder including serious family, social, and legal problems.”
Advancing Knowledge, Findings From the Cohort
The phenomenon of ethanol production by gut microbiota has been known for over a century, Schnabl wrote with two co-authors in a 2024 review in Nature Reviews Gastroenterology & Hepatology of “endogenous ethanol production in health and disease.”
And in recent decades, he said at the meeting, research has linked endogenous ethanol production to MASLD, positioning it as a potential contributor to disease pathogenesis. In one of the most recently published studies, patients with MASLD had higher concentrations of ethanol in their systemic circulation after a mixed meal test than did healthy controls — and even higher ethanol concentrations in their portal vein blood, “suggesting that this ethanol is coming from the gut microbiome,” Schnabl said.
The paper from China that led Schnabl to establish his cohort was spurred on by a patient with both ABS and MASLD cirrhosis. The patient was found to have strains of high alcohol–producing K pneumoniae in the gut microbiome. When the researchers transplanted these strains into mice via fecal microbiota transplantation (FMT), the mice developed MASLD.
Schnabl’s study focused just on ABS, which is alternatively sometimes called gut fermentation syndrome. The 22 patients in his ABS cohort — each of whom provided stool samples corresponding to remission or flare of ABS symptoms — had a median age of 45 years and were predominantly men, slightly overweight and not obese, and without liver disease. (About 48 patients with suspected ABS were screened, and 20 were excluded after an observed glucose challenge failed to establish a diagnosis; 6 withdrew from the study.)
During remission (no symptoms), patients’ mean blood alcohol content (BAC) level was zero, but during a flare, the mean BAC level was 136 mg/dL. “To put it into perspective, the legal limit for driving in the US is 80 mg/dL,” Schnabl said. Within a mean of 4 hours after the oral glucose load used for diagnosis, patients’ mean BAC level was 73 mg/dL, he noted.
To assess ethanol production by the patients’ microbiota, Schnabl and his team cultured the stool samples — anaerobically adding glucose and measuring ethanol production — and compared the results with findings from stool samples collected from household partners who generally were of the opposite sex. Among their findings: cultures of stool from patients experiencing a flare produced significantly more ethanol than stool from household partners and samples from patients in remission.
To assess whether ethanol was produced by bacteria or fungi, the researchers measured ethanol production in cultures treated with either the antifungal amphotericin B or the antibiotic chloramphenicol. “Chloramphenicol clearly decreased the ethanol production,” Schnabl said. “So at least in this culture test, bacteria produced most of the alcohol in our patients.”
Taxonomic profiling, moreover, revealed “significantly elevated levels” of proteobacteria — with relative abundance of Escherichia coli and K pneumoniae — in patients who were flaring, he said. And functional profiling of the fecal microbiota showed much higher activity of fermentation pathways during patients’ flares than in household partners or healthy controls. (Healthy controls were incorporated into the taxonomic and functional profiling parts of the research.)
A Clinical Approach to ABS
Schnabl said at the meeting that stool cultures of both household partners and patients in long-term remission “all produced some low amount of ethanol, which was initially puzzling to us” but became less surprising as he and his colleagues reviewed more of the literature.
Asked during a discussion period whether ABS could explain chronic fatigue, a commonly reported chronic symptom in populations, Schnabl said it’s possible. And in an interview after the meeting, he elaborated. “The literature clearly says ABS is a rare disease, but I argue that more patients may have ABS; they just don’t know it. And I suspect some may have mild symptoms, like brain fog, feeling tired,” he said. “But at this point, this is complete speculation.”
Physicians should “be aware that if a patient has unexplained symptoms that could be aligned with ABS, checking the blood alcohol level” may be warranted, he said in the interview. A PEth (phosphatidylethanol) test — a biomarker test used to check for longer-term alcohol consumption — is an option, but it is important to appreciate it will not discriminate between exogenous alcohol drinking and endogenous ethanol production.
There are no standardized diagnostic tests for ABS, but at the meeting, Schnabl outlined a clinical approach, starting with a standardized oral glucose tolerance challenge test to detect elevated ethanol concentrations.
A fecal yeast test is warranted for diagnosed patients on the basis of some case reports in which ABS symptoms have improved with antifungal treatments. When the fecal yeast test is negative, “ideally you want to identify the ethanol-producing intestinal bacteria in the patient,” he said, using cultures and fecal metagenomics sequencing.
Treatment could then be tailored to the identified microbial strain, with options being selective antibiotics, probiotics and/or prebiotics, and — likely in the future — phages or FMT, he said. (These options, all aimed at restoring gut homeostasis, are also discussed in his 2024 review.)
Schnabl and his team recently performed FMT in a patient with ABS in whom E coli was determined to be producing excessive ethanol. The FMT, performed after antibiotic pretreatment, resulted in decreases in the relative abundance of proteobacteria and E coli levels, lower blood alcohol levels and fermentation enrichment pathways, and normalized liver enzymes.
After 6 months, however, the patient relapsed, and the measurements reversed. “We decided to do FMT every month, and we treated the patient for 6 months,” Schnabl said, noting that ABS had rendered the patient dysfunctional and unable to work. “He has been out of treatment for over a year now and is not flaring any longer.”
Schnabl and Elizabeth Hohmann, MD, at Massachusetts General Hospital, Boston, are currently recruiting patients with confirmed ABS for a National Institutes of Health–funded phase 1 safety and tolerability study of FMT for ABS.
Schnabl disclosed serving as an external scientific advisor/consultant to Ambys Medicines, Boehringer Ingelheim, Gelesis, Mabwell Therapeutics, Surrozen, and Takeda; and as the founder/BOD/BEO of Nterica Bio.
A version of this article appeared on Medscape.com.
WASHINGTON — When a published case of auto-brewery syndrome (ABS) in China — caused by Klebsiella pneumoniae — received widespread publicity in 2019, patients reacted, sending emails to lead author Jing Yuan, in Beijing, China. Many of these inquiries were from patients in the United States who believed they might have ABS.
“Can you check to see if I have ABS?” patients asked Yuan.
For help, Yuan contacted Bernd Schnabl, MD, AGAF, at the University of California, San Diego, whose research was addressing alcohol-associated liver disease and who was also interested in the gut-liver axis and the role of gut microbiome–derived ethanol in metabolic dysfunction–associated steatotic liver disease (MASLD).
“She asked me, ‘Are you interested in looking into ABS?” Schnabl recalled at the Gut Microbiota for Health (GMFH) World Summit 2025. He dug in and formed what may be the largest research cohort thus far of patients with ABS — a group of 22 patients with their diagnosis confirmed through observed glucose challenge.
His soon-to-be-published
ABS is considered a rare condition, but “I’d argue that it’s rarely diagnosed because many physicians don’t know of the diagnosis, and many are actually very skeptical about the disease,” Schnabl said at the meeting, convened by AGA and the European Society of Neurogastroenterology and Motility.
Patients experience symptoms of intoxication when ethanol produced by dysregulated gut microbiota exceeds the capacity of the liver to metabolize it and accumulates in the blood, he explained.
“Patients constantly talk about brain fog; they can’t concentrate, and it can be very severe,” he said. “They don’t get a firm diagnosis and go from one medical center to another, and they also suffer from complications of alcohol use disorder including serious family, social, and legal problems.”
Advancing Knowledge, Findings From the Cohort
The phenomenon of ethanol production by gut microbiota has been known for over a century, Schnabl wrote with two co-authors in a 2024 review in Nature Reviews Gastroenterology & Hepatology of “endogenous ethanol production in health and disease.”
And in recent decades, he said at the meeting, research has linked endogenous ethanol production to MASLD, positioning it as a potential contributor to disease pathogenesis. In one of the most recently published studies, patients with MASLD had higher concentrations of ethanol in their systemic circulation after a mixed meal test than did healthy controls — and even higher ethanol concentrations in their portal vein blood, “suggesting that this ethanol is coming from the gut microbiome,” Schnabl said.
The paper from China that led Schnabl to establish his cohort was spurred on by a patient with both ABS and MASLD cirrhosis. The patient was found to have strains of high alcohol–producing K pneumoniae in the gut microbiome. When the researchers transplanted these strains into mice via fecal microbiota transplantation (FMT), the mice developed MASLD.
Schnabl’s study focused just on ABS, which is alternatively sometimes called gut fermentation syndrome. The 22 patients in his ABS cohort — each of whom provided stool samples corresponding to remission or flare of ABS symptoms — had a median age of 45 years and were predominantly men, slightly overweight and not obese, and without liver disease. (About 48 patients with suspected ABS were screened, and 20 were excluded after an observed glucose challenge failed to establish a diagnosis; 6 withdrew from the study.)
During remission (no symptoms), patients’ mean blood alcohol content (BAC) level was zero, but during a flare, the mean BAC level was 136 mg/dL. “To put it into perspective, the legal limit for driving in the US is 80 mg/dL,” Schnabl said. Within a mean of 4 hours after the oral glucose load used for diagnosis, patients’ mean BAC level was 73 mg/dL, he noted.
To assess ethanol production by the patients’ microbiota, Schnabl and his team cultured the stool samples — anaerobically adding glucose and measuring ethanol production — and compared the results with findings from stool samples collected from household partners who generally were of the opposite sex. Among their findings: cultures of stool from patients experiencing a flare produced significantly more ethanol than stool from household partners and samples from patients in remission.
To assess whether ethanol was produced by bacteria or fungi, the researchers measured ethanol production in cultures treated with either the antifungal amphotericin B or the antibiotic chloramphenicol. “Chloramphenicol clearly decreased the ethanol production,” Schnabl said. “So at least in this culture test, bacteria produced most of the alcohol in our patients.”
Taxonomic profiling, moreover, revealed “significantly elevated levels” of proteobacteria — with relative abundance of Escherichia coli and K pneumoniae — in patients who were flaring, he said. And functional profiling of the fecal microbiota showed much higher activity of fermentation pathways during patients’ flares than in household partners or healthy controls. (Healthy controls were incorporated into the taxonomic and functional profiling parts of the research.)
A Clinical Approach to ABS
Schnabl said at the meeting that stool cultures of both household partners and patients in long-term remission “all produced some low amount of ethanol, which was initially puzzling to us” but became less surprising as he and his colleagues reviewed more of the literature.
Asked during a discussion period whether ABS could explain chronic fatigue, a commonly reported chronic symptom in populations, Schnabl said it’s possible. And in an interview after the meeting, he elaborated. “The literature clearly says ABS is a rare disease, but I argue that more patients may have ABS; they just don’t know it. And I suspect some may have mild symptoms, like brain fog, feeling tired,” he said. “But at this point, this is complete speculation.”
Physicians should “be aware that if a patient has unexplained symptoms that could be aligned with ABS, checking the blood alcohol level” may be warranted, he said in the interview. A PEth (phosphatidylethanol) test — a biomarker test used to check for longer-term alcohol consumption — is an option, but it is important to appreciate it will not discriminate between exogenous alcohol drinking and endogenous ethanol production.
There are no standardized diagnostic tests for ABS, but at the meeting, Schnabl outlined a clinical approach, starting with a standardized oral glucose tolerance challenge test to detect elevated ethanol concentrations.
A fecal yeast test is warranted for diagnosed patients on the basis of some case reports in which ABS symptoms have improved with antifungal treatments. When the fecal yeast test is negative, “ideally you want to identify the ethanol-producing intestinal bacteria in the patient,” he said, using cultures and fecal metagenomics sequencing.
Treatment could then be tailored to the identified microbial strain, with options being selective antibiotics, probiotics and/or prebiotics, and — likely in the future — phages or FMT, he said. (These options, all aimed at restoring gut homeostasis, are also discussed in his 2024 review.)
Schnabl and his team recently performed FMT in a patient with ABS in whom E coli was determined to be producing excessive ethanol. The FMT, performed after antibiotic pretreatment, resulted in decreases in the relative abundance of proteobacteria and E coli levels, lower blood alcohol levels and fermentation enrichment pathways, and normalized liver enzymes.
After 6 months, however, the patient relapsed, and the measurements reversed. “We decided to do FMT every month, and we treated the patient for 6 months,” Schnabl said, noting that ABS had rendered the patient dysfunctional and unable to work. “He has been out of treatment for over a year now and is not flaring any longer.”
Schnabl and Elizabeth Hohmann, MD, at Massachusetts General Hospital, Boston, are currently recruiting patients with confirmed ABS for a National Institutes of Health–funded phase 1 safety and tolerability study of FMT for ABS.
Schnabl disclosed serving as an external scientific advisor/consultant to Ambys Medicines, Boehringer Ingelheim, Gelesis, Mabwell Therapeutics, Surrozen, and Takeda; and as the founder/BOD/BEO of Nterica Bio.
A version of this article appeared on Medscape.com.
WASHINGTON — When a published case of auto-brewery syndrome (ABS) in China — caused by Klebsiella pneumoniae — received widespread publicity in 2019, patients reacted, sending emails to lead author Jing Yuan, in Beijing, China. Many of these inquiries were from patients in the United States who believed they might have ABS.
“Can you check to see if I have ABS?” patients asked Yuan.
For help, Yuan contacted Bernd Schnabl, MD, AGAF, at the University of California, San Diego, whose research was addressing alcohol-associated liver disease and who was also interested in the gut-liver axis and the role of gut microbiome–derived ethanol in metabolic dysfunction–associated steatotic liver disease (MASLD).
“She asked me, ‘Are you interested in looking into ABS?” Schnabl recalled at the Gut Microbiota for Health (GMFH) World Summit 2025. He dug in and formed what may be the largest research cohort thus far of patients with ABS — a group of 22 patients with their diagnosis confirmed through observed glucose challenge.
His soon-to-be-published
ABS is considered a rare condition, but “I’d argue that it’s rarely diagnosed because many physicians don’t know of the diagnosis, and many are actually very skeptical about the disease,” Schnabl said at the meeting, convened by AGA and the European Society of Neurogastroenterology and Motility.
Patients experience symptoms of intoxication when ethanol produced by dysregulated gut microbiota exceeds the capacity of the liver to metabolize it and accumulates in the blood, he explained.
“Patients constantly talk about brain fog; they can’t concentrate, and it can be very severe,” he said. “They don’t get a firm diagnosis and go from one medical center to another, and they also suffer from complications of alcohol use disorder including serious family, social, and legal problems.”
Advancing Knowledge, Findings From the Cohort
The phenomenon of ethanol production by gut microbiota has been known for over a century, Schnabl wrote with two co-authors in a 2024 review in Nature Reviews Gastroenterology & Hepatology of “endogenous ethanol production in health and disease.”
And in recent decades, he said at the meeting, research has linked endogenous ethanol production to MASLD, positioning it as a potential contributor to disease pathogenesis. In one of the most recently published studies, patients with MASLD had higher concentrations of ethanol in their systemic circulation after a mixed meal test than did healthy controls — and even higher ethanol concentrations in their portal vein blood, “suggesting that this ethanol is coming from the gut microbiome,” Schnabl said.
The paper from China that led Schnabl to establish his cohort was spurred on by a patient with both ABS and MASLD cirrhosis. The patient was found to have strains of high alcohol–producing K pneumoniae in the gut microbiome. When the researchers transplanted these strains into mice via fecal microbiota transplantation (FMT), the mice developed MASLD.
Schnabl’s study focused just on ABS, which is alternatively sometimes called gut fermentation syndrome. The 22 patients in his ABS cohort — each of whom provided stool samples corresponding to remission or flare of ABS symptoms — had a median age of 45 years and were predominantly men, slightly overweight and not obese, and without liver disease. (About 48 patients with suspected ABS were screened, and 20 were excluded after an observed glucose challenge failed to establish a diagnosis; 6 withdrew from the study.)
During remission (no symptoms), patients’ mean blood alcohol content (BAC) level was zero, but during a flare, the mean BAC level was 136 mg/dL. “To put it into perspective, the legal limit for driving in the US is 80 mg/dL,” Schnabl said. Within a mean of 4 hours after the oral glucose load used for diagnosis, patients’ mean BAC level was 73 mg/dL, he noted.
To assess ethanol production by the patients’ microbiota, Schnabl and his team cultured the stool samples — anaerobically adding glucose and measuring ethanol production — and compared the results with findings from stool samples collected from household partners who generally were of the opposite sex. Among their findings: cultures of stool from patients experiencing a flare produced significantly more ethanol than stool from household partners and samples from patients in remission.
To assess whether ethanol was produced by bacteria or fungi, the researchers measured ethanol production in cultures treated with either the antifungal amphotericin B or the antibiotic chloramphenicol. “Chloramphenicol clearly decreased the ethanol production,” Schnabl said. “So at least in this culture test, bacteria produced most of the alcohol in our patients.”
Taxonomic profiling, moreover, revealed “significantly elevated levels” of proteobacteria — with relative abundance of Escherichia coli and K pneumoniae — in patients who were flaring, he said. And functional profiling of the fecal microbiota showed much higher activity of fermentation pathways during patients’ flares than in household partners or healthy controls. (Healthy controls were incorporated into the taxonomic and functional profiling parts of the research.)
A Clinical Approach to ABS
Schnabl said at the meeting that stool cultures of both household partners and patients in long-term remission “all produced some low amount of ethanol, which was initially puzzling to us” but became less surprising as he and his colleagues reviewed more of the literature.
Asked during a discussion period whether ABS could explain chronic fatigue, a commonly reported chronic symptom in populations, Schnabl said it’s possible. And in an interview after the meeting, he elaborated. “The literature clearly says ABS is a rare disease, but I argue that more patients may have ABS; they just don’t know it. And I suspect some may have mild symptoms, like brain fog, feeling tired,” he said. “But at this point, this is complete speculation.”
Physicians should “be aware that if a patient has unexplained symptoms that could be aligned with ABS, checking the blood alcohol level” may be warranted, he said in the interview. A PEth (phosphatidylethanol) test — a biomarker test used to check for longer-term alcohol consumption — is an option, but it is important to appreciate it will not discriminate between exogenous alcohol drinking and endogenous ethanol production.
There are no standardized diagnostic tests for ABS, but at the meeting, Schnabl outlined a clinical approach, starting with a standardized oral glucose tolerance challenge test to detect elevated ethanol concentrations.
A fecal yeast test is warranted for diagnosed patients on the basis of some case reports in which ABS symptoms have improved with antifungal treatments. When the fecal yeast test is negative, “ideally you want to identify the ethanol-producing intestinal bacteria in the patient,” he said, using cultures and fecal metagenomics sequencing.
Treatment could then be tailored to the identified microbial strain, with options being selective antibiotics, probiotics and/or prebiotics, and — likely in the future — phages or FMT, he said. (These options, all aimed at restoring gut homeostasis, are also discussed in his 2024 review.)
Schnabl and his team recently performed FMT in a patient with ABS in whom E coli was determined to be producing excessive ethanol. The FMT, performed after antibiotic pretreatment, resulted in decreases in the relative abundance of proteobacteria and E coli levels, lower blood alcohol levels and fermentation enrichment pathways, and normalized liver enzymes.
After 6 months, however, the patient relapsed, and the measurements reversed. “We decided to do FMT every month, and we treated the patient for 6 months,” Schnabl said, noting that ABS had rendered the patient dysfunctional and unable to work. “He has been out of treatment for over a year now and is not flaring any longer.”
Schnabl and Elizabeth Hohmann, MD, at Massachusetts General Hospital, Boston, are currently recruiting patients with confirmed ABS for a National Institutes of Health–funded phase 1 safety and tolerability study of FMT for ABS.
Schnabl disclosed serving as an external scientific advisor/consultant to Ambys Medicines, Boehringer Ingelheim, Gelesis, Mabwell Therapeutics, Surrozen, and Takeda; and as the founder/BOD/BEO of Nterica Bio.
A version of this article appeared on Medscape.com.
FROM GMFH 2025
Elemental Diet Eases Symptoms in Microbiome Gastro Disorders
, according to a new study.
“Elemental diets have long shown promise for treating gastrointestinal disorders like Crohn’s disease, eosinophilic esophagitis, SIBO (small intestinal bacterial overgrowth), and IMO (intestinal methanogen overgrowth), but poor palatability has limited their use,” lead author Ali Rezaie, MD, medical director of the Gastrointestinal (GI) Motility Program and director of Bioinformatics at Cedars-Sinai Medical Center, Los Angeles, told GI & Hepatology News.
Elemental diets are specialized formulas tailored to meet an individual’s specific nutritional needs and daily requirements for vitamins, minerals, fat, free amino acids, and carbohydrates.
In SIBO and IMO specifically, only about half the patients respond to antibiotics, and many require repeat treatments, which underscores the need for effective nonantibiotic alternatives, said Rezaie. “This is the first prospective trial using a PED, aiming to make this approach both viable and accessible for patients,” he noted.
Assessing a Novel Diet in IMO and SIBO
In the study, which was recently published in Clinical Gastroenterology and Hepatology, Rezaie and colleagues enrolled 30 adults with IMO (40%), SIBO (20%), or both (40%). The mean participant age was 45 years, and 63% were women.
All participants completed 2 weeks of a PED, transitioned to 2-3 days of a bland diet, and then resumed their regular diets for 2 weeks.
The diet consisted of multiple 300-calorie packets, adjusted for individual caloric needs. Participants could consume additional packets for hunger but were prohibited from eating other foods. There was no restriction on water intake.
The primary endpoint was changes in stool microbiome after the PED and reintroduction of regular food. Secondary endpoints included lactose breath test normalization to determine bacterial overgrowth in the gut, symptom response, and adverse events.
Researchers collected 29 stool samples at baseline, 27 post-PED, and 27 at study conclusion (2 weeks post-diet).
Key Outcomes
Although the stool samples’ alpha diversity decreased after the PED, the difference was not statistically significant at the end of the study. However, 30 bacterial families showed significant differences in relative abundance post-PED.
Daily symptom severity improved significantly during the second week of the diet compared with baseline, with reduction in abdominal discomfort, bloating, distention, constipation, and flatulence. Further significant improvements in measures such as abdominal pain, diarrhea, fatigue, urgency, and brain fog were observed after reintroducing regular food.
“We observed 73% breath test normalization and 83% global symptom relief — with 100% adherence and tolerance to 2 weeks of exclusive PED,” Rezaie told GI & Hepatology News. No serious adverse events occurred during the study, he added.
Lactose breath test normalization rates post-PED were 58% in patients with IMO, 100% in patients with SIBO, and 75% in those with both conditions.
The extent of patient response to PED was notable, given that 83% had failed prior treatments, Rezaie said.
“While we expected benefit based on palatability improvements and prior retrospective data, the rapid reduction in methane and hydrogen gas — and the sustained microbiome modulation even after reintroducing a regular diet — exceeded expectations,” he said. A significant reduction in visceral fat was another novel finding.
“This study reinforces the power of diet as a therapeutic tool,” Rezaie said, adding that the results show that elemental diets can be palatable, thereby improving patient adherence, tolerance, and, eventually, effectiveness. This is particularly valuable for patients with SIBO and IMO who do not tolerate or respond to antibiotics, prefer nonpharmacologic options, or experience recurrent symptoms after antibiotic treatment.
Limitations and Next Steps
Study limitations included the lack of a placebo group with a sham diet, the short follow-up after reintroducing a regular diet, and the inability to assess microbial gene function.
However, the results support the safety, tolerance, and benefit of a PED in patients with IMO/SIBO. Personalized dietary interventions that support the growth of beneficial bacteria may be an effective approach to treating these disorders, Rezaie and colleagues noted in their publication.
Although the current study is a promising first step, longer-term studies are needed to evaluate the durability of microbiome and symptom improvements, Rezaie said.
Making the Most of Microbiome Manipulation
Elemental diets may help modulate the gut microbiome while reducing immune activation, making them attractive for microbiome-targeted gastrointestinal therapies, Jatin Roper, MD, a gastroenterologist at Duke University, Durham, North Carolina, told GI & Hepatology News.
“Antibiotics are only effective in half of SIBO cases and often require retreatment, so better therapies are needed,” said Roper, who was not affiliated with the study. He added that its findings confirmed the researchers’ hypothesis that a PED can be both safe and effective in patients with SIBO.
Roper noted the 83% symptom improvement as the study’s most unexpected and encouraging finding, as it represents a substantial improvement compared with standard antibiotic therapy. “It is also surprising that the tolerance rate of the elemental diet in this study was 100%,” he said.
However, diet palatability remains a major barrier in real-world practice.
“Adherence rates are likely to be far lower than in trials in which patients are closely monitored, and this challenge will not be easily overcome,” he added.
The study’s limitations, including the lack of metagenomic analysis and a placebo group, are important to address in future research, Roper said. In particular, controlled trials of elemental diets are needed to determine whether microbiome changes are directly responsible for symptom improvement.
The study was supported in part by Good LFE and the John and Geraldine Cusenza Foundation. Rezaie disclosed serving as a consultant/speaker for Bausch Health and having equity in Dieta Health, Gemelli Biotech, and Good LFE. Roper had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
, according to a new study.
“Elemental diets have long shown promise for treating gastrointestinal disorders like Crohn’s disease, eosinophilic esophagitis, SIBO (small intestinal bacterial overgrowth), and IMO (intestinal methanogen overgrowth), but poor palatability has limited their use,” lead author Ali Rezaie, MD, medical director of the Gastrointestinal (GI) Motility Program and director of Bioinformatics at Cedars-Sinai Medical Center, Los Angeles, told GI & Hepatology News.
Elemental diets are specialized formulas tailored to meet an individual’s specific nutritional needs and daily requirements for vitamins, minerals, fat, free amino acids, and carbohydrates.
In SIBO and IMO specifically, only about half the patients respond to antibiotics, and many require repeat treatments, which underscores the need for effective nonantibiotic alternatives, said Rezaie. “This is the first prospective trial using a PED, aiming to make this approach both viable and accessible for patients,” he noted.
Assessing a Novel Diet in IMO and SIBO
In the study, which was recently published in Clinical Gastroenterology and Hepatology, Rezaie and colleagues enrolled 30 adults with IMO (40%), SIBO (20%), or both (40%). The mean participant age was 45 years, and 63% were women.
All participants completed 2 weeks of a PED, transitioned to 2-3 days of a bland diet, and then resumed their regular diets for 2 weeks.
The diet consisted of multiple 300-calorie packets, adjusted for individual caloric needs. Participants could consume additional packets for hunger but were prohibited from eating other foods. There was no restriction on water intake.
The primary endpoint was changes in stool microbiome after the PED and reintroduction of regular food. Secondary endpoints included lactose breath test normalization to determine bacterial overgrowth in the gut, symptom response, and adverse events.
Researchers collected 29 stool samples at baseline, 27 post-PED, and 27 at study conclusion (2 weeks post-diet).
Key Outcomes
Although the stool samples’ alpha diversity decreased after the PED, the difference was not statistically significant at the end of the study. However, 30 bacterial families showed significant differences in relative abundance post-PED.
Daily symptom severity improved significantly during the second week of the diet compared with baseline, with reduction in abdominal discomfort, bloating, distention, constipation, and flatulence. Further significant improvements in measures such as abdominal pain, diarrhea, fatigue, urgency, and brain fog were observed after reintroducing regular food.
“We observed 73% breath test normalization and 83% global symptom relief — with 100% adherence and tolerance to 2 weeks of exclusive PED,” Rezaie told GI & Hepatology News. No serious adverse events occurred during the study, he added.
Lactose breath test normalization rates post-PED were 58% in patients with IMO, 100% in patients with SIBO, and 75% in those with both conditions.
The extent of patient response to PED was notable, given that 83% had failed prior treatments, Rezaie said.
“While we expected benefit based on palatability improvements and prior retrospective data, the rapid reduction in methane and hydrogen gas — and the sustained microbiome modulation even after reintroducing a regular diet — exceeded expectations,” he said. A significant reduction in visceral fat was another novel finding.
“This study reinforces the power of diet as a therapeutic tool,” Rezaie said, adding that the results show that elemental diets can be palatable, thereby improving patient adherence, tolerance, and, eventually, effectiveness. This is particularly valuable for patients with SIBO and IMO who do not tolerate or respond to antibiotics, prefer nonpharmacologic options, or experience recurrent symptoms after antibiotic treatment.
Limitations and Next Steps
Study limitations included the lack of a placebo group with a sham diet, the short follow-up after reintroducing a regular diet, and the inability to assess microbial gene function.
However, the results support the safety, tolerance, and benefit of a PED in patients with IMO/SIBO. Personalized dietary interventions that support the growth of beneficial bacteria may be an effective approach to treating these disorders, Rezaie and colleagues noted in their publication.
Although the current study is a promising first step, longer-term studies are needed to evaluate the durability of microbiome and symptom improvements, Rezaie said.
Making the Most of Microbiome Manipulation
Elemental diets may help modulate the gut microbiome while reducing immune activation, making them attractive for microbiome-targeted gastrointestinal therapies, Jatin Roper, MD, a gastroenterologist at Duke University, Durham, North Carolina, told GI & Hepatology News.
“Antibiotics are only effective in half of SIBO cases and often require retreatment, so better therapies are needed,” said Roper, who was not affiliated with the study. He added that its findings confirmed the researchers’ hypothesis that a PED can be both safe and effective in patients with SIBO.
Roper noted the 83% symptom improvement as the study’s most unexpected and encouraging finding, as it represents a substantial improvement compared with standard antibiotic therapy. “It is also surprising that the tolerance rate of the elemental diet in this study was 100%,” he said.
However, diet palatability remains a major barrier in real-world practice.
“Adherence rates are likely to be far lower than in trials in which patients are closely monitored, and this challenge will not be easily overcome,” he added.
The study’s limitations, including the lack of metagenomic analysis and a placebo group, are important to address in future research, Roper said. In particular, controlled trials of elemental diets are needed to determine whether microbiome changes are directly responsible for symptom improvement.
The study was supported in part by Good LFE and the John and Geraldine Cusenza Foundation. Rezaie disclosed serving as a consultant/speaker for Bausch Health and having equity in Dieta Health, Gemelli Biotech, and Good LFE. Roper had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
, according to a new study.
“Elemental diets have long shown promise for treating gastrointestinal disorders like Crohn’s disease, eosinophilic esophagitis, SIBO (small intestinal bacterial overgrowth), and IMO (intestinal methanogen overgrowth), but poor palatability has limited their use,” lead author Ali Rezaie, MD, medical director of the Gastrointestinal (GI) Motility Program and director of Bioinformatics at Cedars-Sinai Medical Center, Los Angeles, told GI & Hepatology News.
Elemental diets are specialized formulas tailored to meet an individual’s specific nutritional needs and daily requirements for vitamins, minerals, fat, free amino acids, and carbohydrates.
In SIBO and IMO specifically, only about half the patients respond to antibiotics, and many require repeat treatments, which underscores the need for effective nonantibiotic alternatives, said Rezaie. “This is the first prospective trial using a PED, aiming to make this approach both viable and accessible for patients,” he noted.
Assessing a Novel Diet in IMO and SIBO
In the study, which was recently published in Clinical Gastroenterology and Hepatology, Rezaie and colleagues enrolled 30 adults with IMO (40%), SIBO (20%), or both (40%). The mean participant age was 45 years, and 63% were women.
All participants completed 2 weeks of a PED, transitioned to 2-3 days of a bland diet, and then resumed their regular diets for 2 weeks.
The diet consisted of multiple 300-calorie packets, adjusted for individual caloric needs. Participants could consume additional packets for hunger but were prohibited from eating other foods. There was no restriction on water intake.
The primary endpoint was changes in stool microbiome after the PED and reintroduction of regular food. Secondary endpoints included lactose breath test normalization to determine bacterial overgrowth in the gut, symptom response, and adverse events.
Researchers collected 29 stool samples at baseline, 27 post-PED, and 27 at study conclusion (2 weeks post-diet).
Key Outcomes
Although the stool samples’ alpha diversity decreased after the PED, the difference was not statistically significant at the end of the study. However, 30 bacterial families showed significant differences in relative abundance post-PED.
Daily symptom severity improved significantly during the second week of the diet compared with baseline, with reduction in abdominal discomfort, bloating, distention, constipation, and flatulence. Further significant improvements in measures such as abdominal pain, diarrhea, fatigue, urgency, and brain fog were observed after reintroducing regular food.
“We observed 73% breath test normalization and 83% global symptom relief — with 100% adherence and tolerance to 2 weeks of exclusive PED,” Rezaie told GI & Hepatology News. No serious adverse events occurred during the study, he added.
Lactose breath test normalization rates post-PED were 58% in patients with IMO, 100% in patients with SIBO, and 75% in those with both conditions.
The extent of patient response to PED was notable, given that 83% had failed prior treatments, Rezaie said.
“While we expected benefit based on palatability improvements and prior retrospective data, the rapid reduction in methane and hydrogen gas — and the sustained microbiome modulation even after reintroducing a regular diet — exceeded expectations,” he said. A significant reduction in visceral fat was another novel finding.
“This study reinforces the power of diet as a therapeutic tool,” Rezaie said, adding that the results show that elemental diets can be palatable, thereby improving patient adherence, tolerance, and, eventually, effectiveness. This is particularly valuable for patients with SIBO and IMO who do not tolerate or respond to antibiotics, prefer nonpharmacologic options, or experience recurrent symptoms after antibiotic treatment.
Limitations and Next Steps
Study limitations included the lack of a placebo group with a sham diet, the short follow-up after reintroducing a regular diet, and the inability to assess microbial gene function.
However, the results support the safety, tolerance, and benefit of a PED in patients with IMO/SIBO. Personalized dietary interventions that support the growth of beneficial bacteria may be an effective approach to treating these disorders, Rezaie and colleagues noted in their publication.
Although the current study is a promising first step, longer-term studies are needed to evaluate the durability of microbiome and symptom improvements, Rezaie said.
Making the Most of Microbiome Manipulation
Elemental diets may help modulate the gut microbiome while reducing immune activation, making them attractive for microbiome-targeted gastrointestinal therapies, Jatin Roper, MD, a gastroenterologist at Duke University, Durham, North Carolina, told GI & Hepatology News.
“Antibiotics are only effective in half of SIBO cases and often require retreatment, so better therapies are needed,” said Roper, who was not affiliated with the study. He added that its findings confirmed the researchers’ hypothesis that a PED can be both safe and effective in patients with SIBO.
Roper noted the 83% symptom improvement as the study’s most unexpected and encouraging finding, as it represents a substantial improvement compared with standard antibiotic therapy. “It is also surprising that the tolerance rate of the elemental diet in this study was 100%,” he said.
However, diet palatability remains a major barrier in real-world practice.
“Adherence rates are likely to be far lower than in trials in which patients are closely monitored, and this challenge will not be easily overcome,” he added.
The study’s limitations, including the lack of metagenomic analysis and a placebo group, are important to address in future research, Roper said. In particular, controlled trials of elemental diets are needed to determine whether microbiome changes are directly responsible for symptom improvement.
The study was supported in part by Good LFE and the John and Geraldine Cusenza Foundation. Rezaie disclosed serving as a consultant/speaker for Bausch Health and having equity in Dieta Health, Gemelli Biotech, and Good LFE. Roper had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
The Extra-Bacterial Gut Ecosystem: The Influence of Phages and Fungi in the Microbiome
WASHINGTON, DC — Research on the gut microbiome — and clinical attention to it — has focused mainly on bacteria, but bacteriophages and fungi play critical roles as well, with significant influences on health and disease, experts said at the Gut Microbiota for Health (GMFH) World Summit 2025.
Fungi account for < 1% of the total genetic material in the microbiome but 1%-2% of its total biomass. “Despite their relative rarity, they have an important and outsized influence on gut health” — an impact that results from their unique interface with the immune system, said Kyla Ost, PhD, of the Anschutz Medical Campus, University of Colorado, in Denver, whose research focuses on this interface.
And bacteriophages — viruses that infect and kill bacteria — are highly abundant in the gut. “Bacteriophages begin to colonize our GI [gastrointestinal] tract at the same time we develop our own microbiome shortly after birth, and from that time on, they interact with the bacteria in our GI tract, shaping [and being shaped by] the bacterial species we carry with us,” said Robert (Chip) Schooley, MD, distinguished professor of medicine at the University of California San Diego School of Medicine.
“We’ve been talking about things that affect the gut microbiome — diet, genetics, immune response — but probably the biggest influence on what grows in the GI tract are bacteriophages,” said Schooley, co-director of the Center for Innovative Phage Applications and Therapeutics, in a session on the extra-bacterial gut ecosystem.
Among the current questions:
‘New life’ for Phage Therapy
Bacteriophages represent a promising approach for the treatment of multidrug resistant bacterial pathogens in an era of increasing resistance and a dried-up antibiotic discovery pipeline, Schooley said. (In 2019, an estimated 4.95 million deaths around the world were associated with bacterial antimicrobial resistance, and by 2050, it has been forecast that this number will rise to an estimated 8.22 million deaths.)
But in addition to suppressing bacterial pathogens causing direct morbidity, phage therapy has the potential to suppress bacteria believed to contribute to chronic diseases, he said. “We have proof-of-concept studies about the ability of phage to modulate bacteria in the digestive tract,” and an increasing number of clinical trials of the use of phages in GI and other diseases are underway, he said.
Phages were discovered just over a century ago, but phage therapy was widely abandoned once antibiotics were developed, except for in Russia and the former Eastern Bloc countries, where phage therapy continued to be used.
Phage therapy “got new life” in the West, Schooley said, about 10-15 years ago with an increasing number of detailed and high-profile case reports, including one in which a UC San Diego colleague, Tom Patterson, PhD, contracted a deadly multidrug resistant bacterial infection in Egypt and was eventually saved with bacteriophage therapy. (The case was the subject of the book The Perfect Predator).
Since then, as described in case reports and studies in the literature, “hundreds of people have been treated with bacteriophages here and in Europe,” most commonly for pulmonary infections and infections in implanted vascular and orthopedic devices, said Schooley, who coauthored a review in Cell in 2023 that describes phage biology and advances and future directions in phage therapy.
The use of bacteriophages to prevent systemic infections during high-risk periods — such as during chemotherapeutic regimens for hematological regimens — is an area of interest, he said at the meeting.
In research that is making its way to a clinical trial of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), researchers screened a library of phages to identify those with broad coverage of Escherichia coli. Using tail fiber engineering and CRISPR technology, they then engineered a combination of the four most complementary bacteriophages to selectively kill E coli — including fluoroquinolone-resistant strains that, in patients whose GI tracts are colonized with these strains, can translocate from the gut into the bloodstream, causing sepsis, during chemotherapeutic regimens for HSCT.
In a mouse model, the CRISPR-enhanced four-phage cocktail (SNIPR001) led to a steady reduction in the E coli colony counts in stool, “showing you can modulate these bacteria in the gut by using bacteriophages to kill them,” Schooley said. Moreover, the CRISPR enhancement strengthened the phages’ ability to break up biofilms, he said, showing “that you can engineer bacteriophages to make them better killers.” A phase 1b/2a study is being planned.
Other Niches for Therapeutic Phages, Challenges
Bacteriophages also could be used to target a gut bacterium that has been shown to attenuate alcoholic liver disease. Patients with alcoholic hepatitis “have a gut microbiome that is different in distribution,” Schooley said, often with increased numbers of Enterococcus faecalis that produce cytolysin, an exotoxin that exacerbates liver injury and is associated with increased mortality.
In published research led by investigators at UC San Diego, stool from cytolysin-positive patients with alcoholic hepatitis was found to exacerbate ethanol-induced liver disease in gnotobiotic mice, and phage therapy against cytolytic E faecalis was found to abolish it, Schooley shared.
Research is also exploring the potential of phage therapy to selectively target adherent invasive E coli in Crohn’s disease, and Klebsiella pneumoniae in the gut microbiome as an exacerbator of inflammatory bowel disease (IBD), he said.
And investigators in Japan, he noted, have reported that bacteriophage therapy against K pneumoniae can ameliorate liver inflammation and disease severity in primary sclerosing cholangitis.
Challenges in the therapeutic use of phages include the narrow host range of phages and an uncertain predictive value of in vitro phage susceptibility testing. “We don’t know yet how to do resistance testing as well as we do with antibiotics,” he said.
In addition, most phages tend to be acid labile, requiring strategies to mitigate inactivation by gastric acid, and there are “major knowledge gaps” relating to phage pharmacology. “We also know that adaptive immune responses to phages can but often doesn’t impact therapy, and we want to understand that better in clinical trials,” Schooley said.
Phages that have a “lysogenic” lifestyle — as opposed to lytic phages which are used therapeutically — can contribute to antibiotic resistance by facilitating the interchange of bacterial resistance genes, he noted.
A Window Into the Mycobiome
The human gut mycobiome is primarily composed of fungi in the Saccharomyces, Candida, and Malassezia genera, with Candida species dominating. Fungal cells harbor distinct immune-stimulatory molecules and activate distinct immune pathways compared with bacteria and other members of the microbiome, said Ost, assistant professor in the immunology and microbiology department of CU Anschutz.
Some fungi, including those in the Candida genus, activate adaptive and innate immune responses that promote metabolic health and protect against infection. A recently published study in Science, for instance, demonstrated that colonization with C dubliniensis in very young mice who had been exposed to broad-spectrum antibiotics promoted “the expansion and development of beta cells in the pancreas” in a macrophage dependent manner, improving metabolic health and reducing diabetes incidence, she shared.
On the one hand, fungi can “exacerbate and perpetuate the pathogenic inflammation that’s found in a growing list of inflammatory diseases” such as IBD. And “in fact, a lot of the benefits and detriments are driven by the exact same species of fungi,” said Ost. “This is particularly true of Candida,” which is a “lifelong colonizer of intestinal microbiota that rarely causes disease but can be quite pathogenic when it does.”
A 2023 review in Nature Reviews Gastroenterology & Hepatology coauthored by Ost describes the role of commensal fungi in intestinal diseases, including IBD, colorectal cancer, and pancreatic cancer.
The pathogenic potential of commensal fungi is largely dependent on its strain, its morphology and its expression of virulence factors, researchers are learning. Ost has studied C albicans, which has been associated with intestinal inflammation and IBD. Like some other Candida species, C albicans are “fascinating shape shifters,” she said, transitioning between a less pathogenic “yeast” morphology and an elongated, adhesive “hyphae” shape that is more pathogenic.
It turns out, according to research by Ost and others, that the C albicans hyphal morphotype — and the adhesins (sticky proteins that facilitate adherence to epithelial cells) and a cytolytic toxin it produces — are preferentially targeted and suppressed by immunoglobulin A (IgA) in the gut.
“Our gut is protected by a large quantity of IgA antibodies…and these IgA interact with the microbiota and play a big role in what microbes are there and the biology of the microbes,” Ost said. Indeed, symptomatic IgA deficiency in humans has been shown to be associated with C albicans overgrowth.
Leveraging the hyphal-specific IgA response to protect against disease seems possible, she said, referring to an experimental anti-Candida fungal vaccine (NDV-3A) designed to induce an adhesin-specific immune response. In a mouse model of colitis, the vaccine protected against C albicans-associated damage. “We saw an immediate IgA response that targeted C albicans in the intestinal contents,” Ost said.
C glabrata, which has also been associated with intestinal inflammation and IBD, does not form hyphae but — depending on the strain — may also induce intestinal IgA responses, she said in describing her recent research.
Ost reported having no disclosures. Schooley disclosed being a consultant for SNIPR Biome, BiomX, Locus, MicrobiotiX, Amazon Data Monitoring Committee: Merck.
A version of this article appeared on Medscape.com.
WASHINGTON, DC — Research on the gut microbiome — and clinical attention to it — has focused mainly on bacteria, but bacteriophages and fungi play critical roles as well, with significant influences on health and disease, experts said at the Gut Microbiota for Health (GMFH) World Summit 2025.
Fungi account for < 1% of the total genetic material in the microbiome but 1%-2% of its total biomass. “Despite their relative rarity, they have an important and outsized influence on gut health” — an impact that results from their unique interface with the immune system, said Kyla Ost, PhD, of the Anschutz Medical Campus, University of Colorado, in Denver, whose research focuses on this interface.
And bacteriophages — viruses that infect and kill bacteria — are highly abundant in the gut. “Bacteriophages begin to colonize our GI [gastrointestinal] tract at the same time we develop our own microbiome shortly after birth, and from that time on, they interact with the bacteria in our GI tract, shaping [and being shaped by] the bacterial species we carry with us,” said Robert (Chip) Schooley, MD, distinguished professor of medicine at the University of California San Diego School of Medicine.
“We’ve been talking about things that affect the gut microbiome — diet, genetics, immune response — but probably the biggest influence on what grows in the GI tract are bacteriophages,” said Schooley, co-director of the Center for Innovative Phage Applications and Therapeutics, in a session on the extra-bacterial gut ecosystem.
Among the current questions:
‘New life’ for Phage Therapy
Bacteriophages represent a promising approach for the treatment of multidrug resistant bacterial pathogens in an era of increasing resistance and a dried-up antibiotic discovery pipeline, Schooley said. (In 2019, an estimated 4.95 million deaths around the world were associated with bacterial antimicrobial resistance, and by 2050, it has been forecast that this number will rise to an estimated 8.22 million deaths.)
But in addition to suppressing bacterial pathogens causing direct morbidity, phage therapy has the potential to suppress bacteria believed to contribute to chronic diseases, he said. “We have proof-of-concept studies about the ability of phage to modulate bacteria in the digestive tract,” and an increasing number of clinical trials of the use of phages in GI and other diseases are underway, he said.
Phages were discovered just over a century ago, but phage therapy was widely abandoned once antibiotics were developed, except for in Russia and the former Eastern Bloc countries, where phage therapy continued to be used.
Phage therapy “got new life” in the West, Schooley said, about 10-15 years ago with an increasing number of detailed and high-profile case reports, including one in which a UC San Diego colleague, Tom Patterson, PhD, contracted a deadly multidrug resistant bacterial infection in Egypt and was eventually saved with bacteriophage therapy. (The case was the subject of the book The Perfect Predator).
Since then, as described in case reports and studies in the literature, “hundreds of people have been treated with bacteriophages here and in Europe,” most commonly for pulmonary infections and infections in implanted vascular and orthopedic devices, said Schooley, who coauthored a review in Cell in 2023 that describes phage biology and advances and future directions in phage therapy.
The use of bacteriophages to prevent systemic infections during high-risk periods — such as during chemotherapeutic regimens for hematological regimens — is an area of interest, he said at the meeting.
In research that is making its way to a clinical trial of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), researchers screened a library of phages to identify those with broad coverage of Escherichia coli. Using tail fiber engineering and CRISPR technology, they then engineered a combination of the four most complementary bacteriophages to selectively kill E coli — including fluoroquinolone-resistant strains that, in patients whose GI tracts are colonized with these strains, can translocate from the gut into the bloodstream, causing sepsis, during chemotherapeutic regimens for HSCT.
In a mouse model, the CRISPR-enhanced four-phage cocktail (SNIPR001) led to a steady reduction in the E coli colony counts in stool, “showing you can modulate these bacteria in the gut by using bacteriophages to kill them,” Schooley said. Moreover, the CRISPR enhancement strengthened the phages’ ability to break up biofilms, he said, showing “that you can engineer bacteriophages to make them better killers.” A phase 1b/2a study is being planned.
Other Niches for Therapeutic Phages, Challenges
Bacteriophages also could be used to target a gut bacterium that has been shown to attenuate alcoholic liver disease. Patients with alcoholic hepatitis “have a gut microbiome that is different in distribution,” Schooley said, often with increased numbers of Enterococcus faecalis that produce cytolysin, an exotoxin that exacerbates liver injury and is associated with increased mortality.
In published research led by investigators at UC San Diego, stool from cytolysin-positive patients with alcoholic hepatitis was found to exacerbate ethanol-induced liver disease in gnotobiotic mice, and phage therapy against cytolytic E faecalis was found to abolish it, Schooley shared.
Research is also exploring the potential of phage therapy to selectively target adherent invasive E coli in Crohn’s disease, and Klebsiella pneumoniae in the gut microbiome as an exacerbator of inflammatory bowel disease (IBD), he said.
And investigators in Japan, he noted, have reported that bacteriophage therapy against K pneumoniae can ameliorate liver inflammation and disease severity in primary sclerosing cholangitis.
Challenges in the therapeutic use of phages include the narrow host range of phages and an uncertain predictive value of in vitro phage susceptibility testing. “We don’t know yet how to do resistance testing as well as we do with antibiotics,” he said.
In addition, most phages tend to be acid labile, requiring strategies to mitigate inactivation by gastric acid, and there are “major knowledge gaps” relating to phage pharmacology. “We also know that adaptive immune responses to phages can but often doesn’t impact therapy, and we want to understand that better in clinical trials,” Schooley said.
Phages that have a “lysogenic” lifestyle — as opposed to lytic phages which are used therapeutically — can contribute to antibiotic resistance by facilitating the interchange of bacterial resistance genes, he noted.
A Window Into the Mycobiome
The human gut mycobiome is primarily composed of fungi in the Saccharomyces, Candida, and Malassezia genera, with Candida species dominating. Fungal cells harbor distinct immune-stimulatory molecules and activate distinct immune pathways compared with bacteria and other members of the microbiome, said Ost, assistant professor in the immunology and microbiology department of CU Anschutz.
Some fungi, including those in the Candida genus, activate adaptive and innate immune responses that promote metabolic health and protect against infection. A recently published study in Science, for instance, demonstrated that colonization with C dubliniensis in very young mice who had been exposed to broad-spectrum antibiotics promoted “the expansion and development of beta cells in the pancreas” in a macrophage dependent manner, improving metabolic health and reducing diabetes incidence, she shared.
On the one hand, fungi can “exacerbate and perpetuate the pathogenic inflammation that’s found in a growing list of inflammatory diseases” such as IBD. And “in fact, a lot of the benefits and detriments are driven by the exact same species of fungi,” said Ost. “This is particularly true of Candida,” which is a “lifelong colonizer of intestinal microbiota that rarely causes disease but can be quite pathogenic when it does.”
A 2023 review in Nature Reviews Gastroenterology & Hepatology coauthored by Ost describes the role of commensal fungi in intestinal diseases, including IBD, colorectal cancer, and pancreatic cancer.
The pathogenic potential of commensal fungi is largely dependent on its strain, its morphology and its expression of virulence factors, researchers are learning. Ost has studied C albicans, which has been associated with intestinal inflammation and IBD. Like some other Candida species, C albicans are “fascinating shape shifters,” she said, transitioning between a less pathogenic “yeast” morphology and an elongated, adhesive “hyphae” shape that is more pathogenic.
It turns out, according to research by Ost and others, that the C albicans hyphal morphotype — and the adhesins (sticky proteins that facilitate adherence to epithelial cells) and a cytolytic toxin it produces — are preferentially targeted and suppressed by immunoglobulin A (IgA) in the gut.
“Our gut is protected by a large quantity of IgA antibodies…and these IgA interact with the microbiota and play a big role in what microbes are there and the biology of the microbes,” Ost said. Indeed, symptomatic IgA deficiency in humans has been shown to be associated with C albicans overgrowth.
Leveraging the hyphal-specific IgA response to protect against disease seems possible, she said, referring to an experimental anti-Candida fungal vaccine (NDV-3A) designed to induce an adhesin-specific immune response. In a mouse model of colitis, the vaccine protected against C albicans-associated damage. “We saw an immediate IgA response that targeted C albicans in the intestinal contents,” Ost said.
C glabrata, which has also been associated with intestinal inflammation and IBD, does not form hyphae but — depending on the strain — may also induce intestinal IgA responses, she said in describing her recent research.
Ost reported having no disclosures. Schooley disclosed being a consultant for SNIPR Biome, BiomX, Locus, MicrobiotiX, Amazon Data Monitoring Committee: Merck.
A version of this article appeared on Medscape.com.
WASHINGTON, DC — Research on the gut microbiome — and clinical attention to it — has focused mainly on bacteria, but bacteriophages and fungi play critical roles as well, with significant influences on health and disease, experts said at the Gut Microbiota for Health (GMFH) World Summit 2025.
Fungi account for < 1% of the total genetic material in the microbiome but 1%-2% of its total biomass. “Despite their relative rarity, they have an important and outsized influence on gut health” — an impact that results from their unique interface with the immune system, said Kyla Ost, PhD, of the Anschutz Medical Campus, University of Colorado, in Denver, whose research focuses on this interface.
And bacteriophages — viruses that infect and kill bacteria — are highly abundant in the gut. “Bacteriophages begin to colonize our GI [gastrointestinal] tract at the same time we develop our own microbiome shortly after birth, and from that time on, they interact with the bacteria in our GI tract, shaping [and being shaped by] the bacterial species we carry with us,” said Robert (Chip) Schooley, MD, distinguished professor of medicine at the University of California San Diego School of Medicine.
“We’ve been talking about things that affect the gut microbiome — diet, genetics, immune response — but probably the biggest influence on what grows in the GI tract are bacteriophages,” said Schooley, co-director of the Center for Innovative Phage Applications and Therapeutics, in a session on the extra-bacterial gut ecosystem.
Among the current questions:
‘New life’ for Phage Therapy
Bacteriophages represent a promising approach for the treatment of multidrug resistant bacterial pathogens in an era of increasing resistance and a dried-up antibiotic discovery pipeline, Schooley said. (In 2019, an estimated 4.95 million deaths around the world were associated with bacterial antimicrobial resistance, and by 2050, it has been forecast that this number will rise to an estimated 8.22 million deaths.)
But in addition to suppressing bacterial pathogens causing direct morbidity, phage therapy has the potential to suppress bacteria believed to contribute to chronic diseases, he said. “We have proof-of-concept studies about the ability of phage to modulate bacteria in the digestive tract,” and an increasing number of clinical trials of the use of phages in GI and other diseases are underway, he said.
Phages were discovered just over a century ago, but phage therapy was widely abandoned once antibiotics were developed, except for in Russia and the former Eastern Bloc countries, where phage therapy continued to be used.
Phage therapy “got new life” in the West, Schooley said, about 10-15 years ago with an increasing number of detailed and high-profile case reports, including one in which a UC San Diego colleague, Tom Patterson, PhD, contracted a deadly multidrug resistant bacterial infection in Egypt and was eventually saved with bacteriophage therapy. (The case was the subject of the book The Perfect Predator).
Since then, as described in case reports and studies in the literature, “hundreds of people have been treated with bacteriophages here and in Europe,” most commonly for pulmonary infections and infections in implanted vascular and orthopedic devices, said Schooley, who coauthored a review in Cell in 2023 that describes phage biology and advances and future directions in phage therapy.
The use of bacteriophages to prevent systemic infections during high-risk periods — such as during chemotherapeutic regimens for hematological regimens — is an area of interest, he said at the meeting.
In research that is making its way to a clinical trial of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), researchers screened a library of phages to identify those with broad coverage of Escherichia coli. Using tail fiber engineering and CRISPR technology, they then engineered a combination of the four most complementary bacteriophages to selectively kill E coli — including fluoroquinolone-resistant strains that, in patients whose GI tracts are colonized with these strains, can translocate from the gut into the bloodstream, causing sepsis, during chemotherapeutic regimens for HSCT.
In a mouse model, the CRISPR-enhanced four-phage cocktail (SNIPR001) led to a steady reduction in the E coli colony counts in stool, “showing you can modulate these bacteria in the gut by using bacteriophages to kill them,” Schooley said. Moreover, the CRISPR enhancement strengthened the phages’ ability to break up biofilms, he said, showing “that you can engineer bacteriophages to make them better killers.” A phase 1b/2a study is being planned.
Other Niches for Therapeutic Phages, Challenges
Bacteriophages also could be used to target a gut bacterium that has been shown to attenuate alcoholic liver disease. Patients with alcoholic hepatitis “have a gut microbiome that is different in distribution,” Schooley said, often with increased numbers of Enterococcus faecalis that produce cytolysin, an exotoxin that exacerbates liver injury and is associated with increased mortality.
In published research led by investigators at UC San Diego, stool from cytolysin-positive patients with alcoholic hepatitis was found to exacerbate ethanol-induced liver disease in gnotobiotic mice, and phage therapy against cytolytic E faecalis was found to abolish it, Schooley shared.
Research is also exploring the potential of phage therapy to selectively target adherent invasive E coli in Crohn’s disease, and Klebsiella pneumoniae in the gut microbiome as an exacerbator of inflammatory bowel disease (IBD), he said.
And investigators in Japan, he noted, have reported that bacteriophage therapy against K pneumoniae can ameliorate liver inflammation and disease severity in primary sclerosing cholangitis.
Challenges in the therapeutic use of phages include the narrow host range of phages and an uncertain predictive value of in vitro phage susceptibility testing. “We don’t know yet how to do resistance testing as well as we do with antibiotics,” he said.
In addition, most phages tend to be acid labile, requiring strategies to mitigate inactivation by gastric acid, and there are “major knowledge gaps” relating to phage pharmacology. “We also know that adaptive immune responses to phages can but often doesn’t impact therapy, and we want to understand that better in clinical trials,” Schooley said.
Phages that have a “lysogenic” lifestyle — as opposed to lytic phages which are used therapeutically — can contribute to antibiotic resistance by facilitating the interchange of bacterial resistance genes, he noted.
A Window Into the Mycobiome
The human gut mycobiome is primarily composed of fungi in the Saccharomyces, Candida, and Malassezia genera, with Candida species dominating. Fungal cells harbor distinct immune-stimulatory molecules and activate distinct immune pathways compared with bacteria and other members of the microbiome, said Ost, assistant professor in the immunology and microbiology department of CU Anschutz.
Some fungi, including those in the Candida genus, activate adaptive and innate immune responses that promote metabolic health and protect against infection. A recently published study in Science, for instance, demonstrated that colonization with C dubliniensis in very young mice who had been exposed to broad-spectrum antibiotics promoted “the expansion and development of beta cells in the pancreas” in a macrophage dependent manner, improving metabolic health and reducing diabetes incidence, she shared.
On the one hand, fungi can “exacerbate and perpetuate the pathogenic inflammation that’s found in a growing list of inflammatory diseases” such as IBD. And “in fact, a lot of the benefits and detriments are driven by the exact same species of fungi,” said Ost. “This is particularly true of Candida,” which is a “lifelong colonizer of intestinal microbiota that rarely causes disease but can be quite pathogenic when it does.”
A 2023 review in Nature Reviews Gastroenterology & Hepatology coauthored by Ost describes the role of commensal fungi in intestinal diseases, including IBD, colorectal cancer, and pancreatic cancer.
The pathogenic potential of commensal fungi is largely dependent on its strain, its morphology and its expression of virulence factors, researchers are learning. Ost has studied C albicans, which has been associated with intestinal inflammation and IBD. Like some other Candida species, C albicans are “fascinating shape shifters,” she said, transitioning between a less pathogenic “yeast” morphology and an elongated, adhesive “hyphae” shape that is more pathogenic.
It turns out, according to research by Ost and others, that the C albicans hyphal morphotype — and the adhesins (sticky proteins that facilitate adherence to epithelial cells) and a cytolytic toxin it produces — are preferentially targeted and suppressed by immunoglobulin A (IgA) in the gut.
“Our gut is protected by a large quantity of IgA antibodies…and these IgA interact with the microbiota and play a big role in what microbes are there and the biology of the microbes,” Ost said. Indeed, symptomatic IgA deficiency in humans has been shown to be associated with C albicans overgrowth.
Leveraging the hyphal-specific IgA response to protect against disease seems possible, she said, referring to an experimental anti-Candida fungal vaccine (NDV-3A) designed to induce an adhesin-specific immune response. In a mouse model of colitis, the vaccine protected against C albicans-associated damage. “We saw an immediate IgA response that targeted C albicans in the intestinal contents,” Ost said.
C glabrata, which has also been associated with intestinal inflammation and IBD, does not form hyphae but — depending on the strain — may also induce intestinal IgA responses, she said in describing her recent research.
Ost reported having no disclosures. Schooley disclosed being a consultant for SNIPR Biome, BiomX, Locus, MicrobiotiX, Amazon Data Monitoring Committee: Merck.
A version of this article appeared on Medscape.com.
FROM GMFH 2025
Wearable Devices May Predict IBD Flares Weeks in Advance
according to investigators.
These findings suggest that widely used consumer wearables could support long-term monitoring of IBD and other chronic inflammatory conditions, lead author Robert P. Hirten, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues reported.
“Wearable devices are an increasingly accepted tool for monitoring health and disease,” the investigators wrote in Gastroenterology. “They are frequently used in non–inflammatory-based diseases for remote patient monitoring, allowing individuals to be monitored outside of the clinical setting, which has resulted in improved outcomes in multiple disease states.”
Progress has been slower for inflammatory conditions, the investigators noted, despite interest from both providers and patients. Prior studies have explored activity and sleep tracking, or sweat-based biomarkers, as potential tools for monitoring IBD.
Hirten and colleagues took a novel approach, focusing on physiologic changes driven by autonomic nervous system dysfunction — a hallmark of chronic inflammation. Conditions like IBD are associated with reduced parasympathetic activity and increased sympathetic tone, which in turn affect heart rate and heart rate variability. Heart rate tends to rise during flares, while heart rate variability decreases.
Their prospective cohort study included 309 adults with Crohn’s disease (n = 196) or ulcerative colitis (n = 113). Participants used their own or a study-provided Apple Watch, Fitbit, or Oura Ring to passively collect physiological data, including heart rate, resting heart rate, heart rate variability, and step count. A subset of Apple Watch users also contributed oxygen saturation data.
Participants also completed daily symptom surveys using a custom smartphone app and reported laboratory values such as C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin, as part of routine care. These data were used to identify symptomatic and inflammatory flare periods.
Over a mean follow-up of about 7 months, the physiological data consistently distinguished both types of flares from periods of remission. Heart rate variability dropped significantly during flares, while heart rate and resting heart rate increased. Step counts decreased during inflammatory flares but not during symptom-only flares. Oxygen saturation stayed mostly the same, except for a slight drop seen in participants with Crohn’s disease.
These physiological changes could be detected as early as 7 weeks before a flare. Predictive models that combined multiple metrics — heart rate variability, heart rate, resting heart rate, and step count — were highly accurate, with F1 scores as high as 0.90 for predicting inflammatory flares and 0.83 for predicting symptomatic flares.
In addition, wearable data helped differentiate between flares caused by active inflammation and those driven by symptoms alone. Even when symptoms were similar, heart rate variability, heart rate, and resting heart rate were significantly higher when inflammation was present—suggesting wearable devices may help address the common mismatch between symptoms and actual disease activity in IBD.
“These findings support the further evaluation of wearable devices in the monitoring of IBD,” the investigators concluded.
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and Ms. Jenny Steingart. The investigators disclosed additional relationships with Agomab, Lilly, Merck, and others.
Dana J. Lukin, MD, PhD, AGAF, of New York-Presbyterian Hospital/Weill Cornell Medicine, New York City, described the study by Hirten et al as “provocative.”
“While the data require a machine learning approach to transform the recorded values into predictive algorithms, it is intriguing that routinely recorded information from smart devices can be used in a manner to inform disease activity,” Lukin said in an interview. “Furthermore, the use of continuously recorded physiological data in this study likely reflects longitudinal health status more accurately than cross-sectional use of patient-reported outcomes or episodic biomarker testing.”
In addition to offering potentially higher accuracy than conventional monitoring, the remote strategy is also more convenient, he noted.
“The use of these devices is likely easier to adhere to than the use of other contemporary monitoring strategies involving the collection of stool or blood samples,” Lukin said. “It may become possible to passively monitor a larger number of patients at risk for flares remotely,” especially given that “almost half of Americans utilize wearables, such as the Apple Watch, Oura Ring, and Fitbit.”
Still, Lukin predicted challenges with widespread adoption.
“More than half of Americans do not routinely [use these devices],” Lukin said. “Cost, access to internet and smartphones, and adoption of new technology may all be barriers to more widespread use.”
He suggested that the present study offers proof of concept, but more prospective data are needed to demonstrate how this type of remote monitoring might improve real-world IBD care.
“Potential studies will assess change in healthcare utilization, corticosteroids, surgery, and clinical flare activity with the use of these data,” Lukin said. “As we learn more about how to handle the large amount of data generated by these devices, our algorithms can be refined to make a feasible platform for practices to employ in routine care.”
Lukin disclosed relationships with Boehringer Ingelheim, Takeda, Vedanta, and others.
Dana J. Lukin, MD, PhD, AGAF, of New York-Presbyterian Hospital/Weill Cornell Medicine, New York City, described the study by Hirten et al as “provocative.”
“While the data require a machine learning approach to transform the recorded values into predictive algorithms, it is intriguing that routinely recorded information from smart devices can be used in a manner to inform disease activity,” Lukin said in an interview. “Furthermore, the use of continuously recorded physiological data in this study likely reflects longitudinal health status more accurately than cross-sectional use of patient-reported outcomes or episodic biomarker testing.”
In addition to offering potentially higher accuracy than conventional monitoring, the remote strategy is also more convenient, he noted.
“The use of these devices is likely easier to adhere to than the use of other contemporary monitoring strategies involving the collection of stool or blood samples,” Lukin said. “It may become possible to passively monitor a larger number of patients at risk for flares remotely,” especially given that “almost half of Americans utilize wearables, such as the Apple Watch, Oura Ring, and Fitbit.”
Still, Lukin predicted challenges with widespread adoption.
“More than half of Americans do not routinely [use these devices],” Lukin said. “Cost, access to internet and smartphones, and adoption of new technology may all be barriers to more widespread use.”
He suggested that the present study offers proof of concept, but more prospective data are needed to demonstrate how this type of remote monitoring might improve real-world IBD care.
“Potential studies will assess change in healthcare utilization, corticosteroids, surgery, and clinical flare activity with the use of these data,” Lukin said. “As we learn more about how to handle the large amount of data generated by these devices, our algorithms can be refined to make a feasible platform for practices to employ in routine care.”
Lukin disclosed relationships with Boehringer Ingelheim, Takeda, Vedanta, and others.
Dana J. Lukin, MD, PhD, AGAF, of New York-Presbyterian Hospital/Weill Cornell Medicine, New York City, described the study by Hirten et al as “provocative.”
“While the data require a machine learning approach to transform the recorded values into predictive algorithms, it is intriguing that routinely recorded information from smart devices can be used in a manner to inform disease activity,” Lukin said in an interview. “Furthermore, the use of continuously recorded physiological data in this study likely reflects longitudinal health status more accurately than cross-sectional use of patient-reported outcomes or episodic biomarker testing.”
In addition to offering potentially higher accuracy than conventional monitoring, the remote strategy is also more convenient, he noted.
“The use of these devices is likely easier to adhere to than the use of other contemporary monitoring strategies involving the collection of stool or blood samples,” Lukin said. “It may become possible to passively monitor a larger number of patients at risk for flares remotely,” especially given that “almost half of Americans utilize wearables, such as the Apple Watch, Oura Ring, and Fitbit.”
Still, Lukin predicted challenges with widespread adoption.
“More than half of Americans do not routinely [use these devices],” Lukin said. “Cost, access to internet and smartphones, and adoption of new technology may all be barriers to more widespread use.”
He suggested that the present study offers proof of concept, but more prospective data are needed to demonstrate how this type of remote monitoring might improve real-world IBD care.
“Potential studies will assess change in healthcare utilization, corticosteroids, surgery, and clinical flare activity with the use of these data,” Lukin said. “As we learn more about how to handle the large amount of data generated by these devices, our algorithms can be refined to make a feasible platform for practices to employ in routine care.”
Lukin disclosed relationships with Boehringer Ingelheim, Takeda, Vedanta, and others.
according to investigators.
These findings suggest that widely used consumer wearables could support long-term monitoring of IBD and other chronic inflammatory conditions, lead author Robert P. Hirten, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues reported.
“Wearable devices are an increasingly accepted tool for monitoring health and disease,” the investigators wrote in Gastroenterology. “They are frequently used in non–inflammatory-based diseases for remote patient monitoring, allowing individuals to be monitored outside of the clinical setting, which has resulted in improved outcomes in multiple disease states.”
Progress has been slower for inflammatory conditions, the investigators noted, despite interest from both providers and patients. Prior studies have explored activity and sleep tracking, or sweat-based biomarkers, as potential tools for monitoring IBD.
Hirten and colleagues took a novel approach, focusing on physiologic changes driven by autonomic nervous system dysfunction — a hallmark of chronic inflammation. Conditions like IBD are associated with reduced parasympathetic activity and increased sympathetic tone, which in turn affect heart rate and heart rate variability. Heart rate tends to rise during flares, while heart rate variability decreases.
Their prospective cohort study included 309 adults with Crohn’s disease (n = 196) or ulcerative colitis (n = 113). Participants used their own or a study-provided Apple Watch, Fitbit, or Oura Ring to passively collect physiological data, including heart rate, resting heart rate, heart rate variability, and step count. A subset of Apple Watch users also contributed oxygen saturation data.
Participants also completed daily symptom surveys using a custom smartphone app and reported laboratory values such as C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin, as part of routine care. These data were used to identify symptomatic and inflammatory flare periods.
Over a mean follow-up of about 7 months, the physiological data consistently distinguished both types of flares from periods of remission. Heart rate variability dropped significantly during flares, while heart rate and resting heart rate increased. Step counts decreased during inflammatory flares but not during symptom-only flares. Oxygen saturation stayed mostly the same, except for a slight drop seen in participants with Crohn’s disease.
These physiological changes could be detected as early as 7 weeks before a flare. Predictive models that combined multiple metrics — heart rate variability, heart rate, resting heart rate, and step count — were highly accurate, with F1 scores as high as 0.90 for predicting inflammatory flares and 0.83 for predicting symptomatic flares.
In addition, wearable data helped differentiate between flares caused by active inflammation and those driven by symptoms alone. Even when symptoms were similar, heart rate variability, heart rate, and resting heart rate were significantly higher when inflammation was present—suggesting wearable devices may help address the common mismatch between symptoms and actual disease activity in IBD.
“These findings support the further evaluation of wearable devices in the monitoring of IBD,” the investigators concluded.
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and Ms. Jenny Steingart. The investigators disclosed additional relationships with Agomab, Lilly, Merck, and others.
according to investigators.
These findings suggest that widely used consumer wearables could support long-term monitoring of IBD and other chronic inflammatory conditions, lead author Robert P. Hirten, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues reported.
“Wearable devices are an increasingly accepted tool for monitoring health and disease,” the investigators wrote in Gastroenterology. “They are frequently used in non–inflammatory-based diseases for remote patient monitoring, allowing individuals to be monitored outside of the clinical setting, which has resulted in improved outcomes in multiple disease states.”
Progress has been slower for inflammatory conditions, the investigators noted, despite interest from both providers and patients. Prior studies have explored activity and sleep tracking, or sweat-based biomarkers, as potential tools for monitoring IBD.
Hirten and colleagues took a novel approach, focusing on physiologic changes driven by autonomic nervous system dysfunction — a hallmark of chronic inflammation. Conditions like IBD are associated with reduced parasympathetic activity and increased sympathetic tone, which in turn affect heart rate and heart rate variability. Heart rate tends to rise during flares, while heart rate variability decreases.
Their prospective cohort study included 309 adults with Crohn’s disease (n = 196) or ulcerative colitis (n = 113). Participants used their own or a study-provided Apple Watch, Fitbit, or Oura Ring to passively collect physiological data, including heart rate, resting heart rate, heart rate variability, and step count. A subset of Apple Watch users also contributed oxygen saturation data.
Participants also completed daily symptom surveys using a custom smartphone app and reported laboratory values such as C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin, as part of routine care. These data were used to identify symptomatic and inflammatory flare periods.
Over a mean follow-up of about 7 months, the physiological data consistently distinguished both types of flares from periods of remission. Heart rate variability dropped significantly during flares, while heart rate and resting heart rate increased. Step counts decreased during inflammatory flares but not during symptom-only flares. Oxygen saturation stayed mostly the same, except for a slight drop seen in participants with Crohn’s disease.
These physiological changes could be detected as early as 7 weeks before a flare. Predictive models that combined multiple metrics — heart rate variability, heart rate, resting heart rate, and step count — were highly accurate, with F1 scores as high as 0.90 for predicting inflammatory flares and 0.83 for predicting symptomatic flares.
In addition, wearable data helped differentiate between flares caused by active inflammation and those driven by symptoms alone. Even when symptoms were similar, heart rate variability, heart rate, and resting heart rate were significantly higher when inflammation was present—suggesting wearable devices may help address the common mismatch between symptoms and actual disease activity in IBD.
“These findings support the further evaluation of wearable devices in the monitoring of IBD,” the investigators concluded.
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and Ms. Jenny Steingart. The investigators disclosed additional relationships with Agomab, Lilly, Merck, and others.
FROM GASTROENTEROLOGY
Gut Microbiome Influences Multiple Neurodegenerative Disorders
WASHINGTON, DC — Age-related neurodegenerative disorders — motor neuron diseases, demyelinating diseases, Alzheimer’s disease, and other proteinopathies — are at an “inflection point,” said researcher Andrea R. Merchak, PhD, with a fuller understanding of disease pathophysiology but an overall dearth of effective disease-modifying treatments.
And this, Merchak said at the Gut Microbiota for Health (GMFH) World Summit 2025, is where the gut microbiome comes in. “The gut-brain axis is important to take into consideration,” she urged, both for gut microbiome researchers — whose collaboration with neurologists and neuroscientists is essential — and for practicing gastroenterologists.
“We are the sum of our environmental exposures,” said Merchak, assistant research professor of neurology at the Indiana University School of Medicine, in Indianapolis. “So for your patient populations, remember you’re not only treating the diseases they’re coming to you with, you’re also treating them for a lifetime of healthy [brain] aging.”
At the center of a healthy aging brain are the brain-residing microglia and peripheral monocytes, she said. These immune cell populations are directly influenced by blood-brain barrier breakdown, inflammation, and gut permeability — and indirectly influenced by microbial products, gastrointestinal (GI) function, and bacterial diversity, Merchak said at the meeting, which was convened by AGA and the European Society of Neurogastroenterology and Motility.
“Many of us grew up learning that the brain is an immune-privileged site, but we’ve been establishing that this is fundamentally not true,” she said. “While the brain does have a privileged status, there are interactions with the blood, with the peripheral immune cells.”
Merchak coauthored a 2024 review in Neurotherapeutics in which she and her colleagues explained that the brain is “heavily connected with peripheral immune dynamics,” and that the gut — as the largest immune organ in the body — is a critical place for peripheral immune development, “thus influencing brain health.”
Gut microbiota interact with the brain via several mechanisms including microbiota-derived metabolites that enter circulation, direct communication via the vagus nerve, and modulation of the immune system, Merchak and her coauthors wrote. Leaky gut, they noted, can lead to an accumulation of inflammatory signals and cells that can exacerbate or induce the onset of neurodegenerative conditions.
As researchers better understand the role that GI dysfunction plays in neurodegenerative disease — as they identify microbiome signatures for predicting risk, for instance — there will be “opportunities to target the microbiome to prevent or reverse dysbiosis as a way to delay, arrest or prevent the onset and progression of neurodegenerative diseases,” they wrote.
At the GMFH meeting, Merchak described both ongoing preclinical research that is dissecting gut-brain communication, and preliminary clinical evidence for the use of gut microbiota-modulating therapies in neurodegenerative disease.
Support for a Gut-Focused Approach
Research on bile acid metabolism in multiple sclerosis (MS) and on peripheral inflammation in dementia exemplify the ongoing preclinical research uncovering the mechanisms of gut-brain communication, Merchak said.
The finding that bile acid metabolism modulates MS autoimmunity comes from research done by Merchak and a team at the University of Virginia, Charlottesville, Virginia, several years ago in which mice with experimental autoimmune encephalomyelitis (EAE) — an animal model of MS — were engineered for T cell specific knockout of the aryl hydrocarbon receptor (AHR). The AHR has been directly tied to MS, and T lymphocytes are known to play a central role in MS pathophysiology.
Blocking the activity of AHR in CD4-positive T cells significantly affected the production of bile acids and other metabolites in the microbiome — and the outcome of central nervous system autoimmunity. “Mice with high levels of bile acids, both primary and secondary, actually recovered from this EAE” and regained motor function, Merchak said at the GMFH meeting.
The potential impact of genetic manipulation on recovery was ruled out — and the role of bile acids confirmed — when, using the EAE model, gut bacteria from mice without AHR were transplanted into mice with AHR. The mice with AHR were able to recover, confirming that AHR can reprogram the gut microbiome and that “high levels of bile acid can lead to reduced autoimmunity in an MS model,” she said.
Other elements and stages of the research, which was published in PLOS Biology in 2023, showed increased apoptosis of CD4-positive immune cells in AHR-deficient mice and the ability of oral taurocholic acid — a bile acid that was especially high in mice without AHR — to reduce the severity of EAE, Merchak said.
Evidence for the role of gut and peripheral inflammation on neurodegeneration is building on numerous fronts, Merchak said. Unpublished research using spatial transcriptomics of colon biopsies from patients with inflammatory bowel disease (IBD), patients with Parkinson’s disease (PD), and neurologically healthy control individuals, for instance, showed similar cell communication patterns in patients with IBD or PD (and no history of IBD) compared with healthy control individuals.
And in research using a single-cell genomics approach and a mouse model of lipopolysaccharide (LPS)-induced system neuroinflammation, microglia were found to preferentially communicate with peripheral myeloid cells rather than other microglia after peripheral LPS exposure.
“In saline-treated mice, the microglia are talking primarily to microglia, but in LPS-treated mice, microglia spend more time communicating with monocytes and T cells,” Merchak explained. “We see communication going from inside the brain to cells coming in from the periphery.”
In another experiment, 2 months of a high-fat, high-sugar diet in mice with an engineered predisposition to frontotemporal dementia led to significant upregulation of major histocompatibility complex class II (MHC II) expression on monocytes in the brain, she said, describing unpublished research. Because MHC II handles antigen presentation in the brain, the change signals increased central-peripheral immune crosstalk and increased brain inflammation.
State of Clinical Research
On the clinical side, Merchak said studies of gut microbiome-modulating therapies are currently not longitudinal enough to accurately study neurodegenerative diseases that may develop over decades. Still, her review of the literature — part of her 2024 article — suggests there is at least some preliminary clinical evidence for the use of probiotics/prebiotics/diet and fecal microbiota transplant (FMT) in several diseases.
- Parkinson’s Disease: “There has been some evidence,” Merchak said at the meeting, “for the treatment [with probiotics, prebiotics and diet] of nonmotor symptoms — things like gastrointestinal distress and mood changes — but no real evidence that such treatments can help with the motor symptoms we see in Parkinson’s.” Over 60 patients with PD have been treated with FMT, she said, with reduced GI distress and mixed results with motor symptoms.
- Alzheimer’s and related dementias: “Diet shows promise for cognitive outcomes, but there hasn’t been much evidence for probiotics,” she said. Her review found 17 patients diagnosed with dementia who were treated with FMT, “and for many of them, maintenance of cognitive function was reported — so no further decline — which is excellent.”
- Multiple Sclerosis: “We see higher quality-of-life measures in patients getting probiotics, prebiotics, and changes in diet,” Merchak said. “Again, most of this [relates to] mood and digestion, but some studies show a slowing of neurological damage as measured by MRI.”
There are reports of 15 patients treated with FMT, and “three of these document full functional recovery,” she said, noting that longer follow-up is necessary as MS is characterized by relapsed and periods of recovery.
Merchak reported no financial disclosures.
A version of this article appeared on Medscape.com.
WASHINGTON, DC — Age-related neurodegenerative disorders — motor neuron diseases, demyelinating diseases, Alzheimer’s disease, and other proteinopathies — are at an “inflection point,” said researcher Andrea R. Merchak, PhD, with a fuller understanding of disease pathophysiology but an overall dearth of effective disease-modifying treatments.
And this, Merchak said at the Gut Microbiota for Health (GMFH) World Summit 2025, is where the gut microbiome comes in. “The gut-brain axis is important to take into consideration,” she urged, both for gut microbiome researchers — whose collaboration with neurologists and neuroscientists is essential — and for practicing gastroenterologists.
“We are the sum of our environmental exposures,” said Merchak, assistant research professor of neurology at the Indiana University School of Medicine, in Indianapolis. “So for your patient populations, remember you’re not only treating the diseases they’re coming to you with, you’re also treating them for a lifetime of healthy [brain] aging.”
At the center of a healthy aging brain are the brain-residing microglia and peripheral monocytes, she said. These immune cell populations are directly influenced by blood-brain barrier breakdown, inflammation, and gut permeability — and indirectly influenced by microbial products, gastrointestinal (GI) function, and bacterial diversity, Merchak said at the meeting, which was convened by AGA and the European Society of Neurogastroenterology and Motility.
“Many of us grew up learning that the brain is an immune-privileged site, but we’ve been establishing that this is fundamentally not true,” she said. “While the brain does have a privileged status, there are interactions with the blood, with the peripheral immune cells.”
Merchak coauthored a 2024 review in Neurotherapeutics in which she and her colleagues explained that the brain is “heavily connected with peripheral immune dynamics,” and that the gut — as the largest immune organ in the body — is a critical place for peripheral immune development, “thus influencing brain health.”
Gut microbiota interact with the brain via several mechanisms including microbiota-derived metabolites that enter circulation, direct communication via the vagus nerve, and modulation of the immune system, Merchak and her coauthors wrote. Leaky gut, they noted, can lead to an accumulation of inflammatory signals and cells that can exacerbate or induce the onset of neurodegenerative conditions.
As researchers better understand the role that GI dysfunction plays in neurodegenerative disease — as they identify microbiome signatures for predicting risk, for instance — there will be “opportunities to target the microbiome to prevent or reverse dysbiosis as a way to delay, arrest or prevent the onset and progression of neurodegenerative diseases,” they wrote.
At the GMFH meeting, Merchak described both ongoing preclinical research that is dissecting gut-brain communication, and preliminary clinical evidence for the use of gut microbiota-modulating therapies in neurodegenerative disease.
Support for a Gut-Focused Approach
Research on bile acid metabolism in multiple sclerosis (MS) and on peripheral inflammation in dementia exemplify the ongoing preclinical research uncovering the mechanisms of gut-brain communication, Merchak said.
The finding that bile acid metabolism modulates MS autoimmunity comes from research done by Merchak and a team at the University of Virginia, Charlottesville, Virginia, several years ago in which mice with experimental autoimmune encephalomyelitis (EAE) — an animal model of MS — were engineered for T cell specific knockout of the aryl hydrocarbon receptor (AHR). The AHR has been directly tied to MS, and T lymphocytes are known to play a central role in MS pathophysiology.
Blocking the activity of AHR in CD4-positive T cells significantly affected the production of bile acids and other metabolites in the microbiome — and the outcome of central nervous system autoimmunity. “Mice with high levels of bile acids, both primary and secondary, actually recovered from this EAE” and regained motor function, Merchak said at the GMFH meeting.
The potential impact of genetic manipulation on recovery was ruled out — and the role of bile acids confirmed — when, using the EAE model, gut bacteria from mice without AHR were transplanted into mice with AHR. The mice with AHR were able to recover, confirming that AHR can reprogram the gut microbiome and that “high levels of bile acid can lead to reduced autoimmunity in an MS model,” she said.
Other elements and stages of the research, which was published in PLOS Biology in 2023, showed increased apoptosis of CD4-positive immune cells in AHR-deficient mice and the ability of oral taurocholic acid — a bile acid that was especially high in mice without AHR — to reduce the severity of EAE, Merchak said.
Evidence for the role of gut and peripheral inflammation on neurodegeneration is building on numerous fronts, Merchak said. Unpublished research using spatial transcriptomics of colon biopsies from patients with inflammatory bowel disease (IBD), patients with Parkinson’s disease (PD), and neurologically healthy control individuals, for instance, showed similar cell communication patterns in patients with IBD or PD (and no history of IBD) compared with healthy control individuals.
And in research using a single-cell genomics approach and a mouse model of lipopolysaccharide (LPS)-induced system neuroinflammation, microglia were found to preferentially communicate with peripheral myeloid cells rather than other microglia after peripheral LPS exposure.
“In saline-treated mice, the microglia are talking primarily to microglia, but in LPS-treated mice, microglia spend more time communicating with monocytes and T cells,” Merchak explained. “We see communication going from inside the brain to cells coming in from the periphery.”
In another experiment, 2 months of a high-fat, high-sugar diet in mice with an engineered predisposition to frontotemporal dementia led to significant upregulation of major histocompatibility complex class II (MHC II) expression on monocytes in the brain, she said, describing unpublished research. Because MHC II handles antigen presentation in the brain, the change signals increased central-peripheral immune crosstalk and increased brain inflammation.
State of Clinical Research
On the clinical side, Merchak said studies of gut microbiome-modulating therapies are currently not longitudinal enough to accurately study neurodegenerative diseases that may develop over decades. Still, her review of the literature — part of her 2024 article — suggests there is at least some preliminary clinical evidence for the use of probiotics/prebiotics/diet and fecal microbiota transplant (FMT) in several diseases.
- Parkinson’s Disease: “There has been some evidence,” Merchak said at the meeting, “for the treatment [with probiotics, prebiotics and diet] of nonmotor symptoms — things like gastrointestinal distress and mood changes — but no real evidence that such treatments can help with the motor symptoms we see in Parkinson’s.” Over 60 patients with PD have been treated with FMT, she said, with reduced GI distress and mixed results with motor symptoms.
- Alzheimer’s and related dementias: “Diet shows promise for cognitive outcomes, but there hasn’t been much evidence for probiotics,” she said. Her review found 17 patients diagnosed with dementia who were treated with FMT, “and for many of them, maintenance of cognitive function was reported — so no further decline — which is excellent.”
- Multiple Sclerosis: “We see higher quality-of-life measures in patients getting probiotics, prebiotics, and changes in diet,” Merchak said. “Again, most of this [relates to] mood and digestion, but some studies show a slowing of neurological damage as measured by MRI.”
There are reports of 15 patients treated with FMT, and “three of these document full functional recovery,” she said, noting that longer follow-up is necessary as MS is characterized by relapsed and periods of recovery.
Merchak reported no financial disclosures.
A version of this article appeared on Medscape.com.
WASHINGTON, DC — Age-related neurodegenerative disorders — motor neuron diseases, demyelinating diseases, Alzheimer’s disease, and other proteinopathies — are at an “inflection point,” said researcher Andrea R. Merchak, PhD, with a fuller understanding of disease pathophysiology but an overall dearth of effective disease-modifying treatments.
And this, Merchak said at the Gut Microbiota for Health (GMFH) World Summit 2025, is where the gut microbiome comes in. “The gut-brain axis is important to take into consideration,” she urged, both for gut microbiome researchers — whose collaboration with neurologists and neuroscientists is essential — and for practicing gastroenterologists.
“We are the sum of our environmental exposures,” said Merchak, assistant research professor of neurology at the Indiana University School of Medicine, in Indianapolis. “So for your patient populations, remember you’re not only treating the diseases they’re coming to you with, you’re also treating them for a lifetime of healthy [brain] aging.”
At the center of a healthy aging brain are the brain-residing microglia and peripheral monocytes, she said. These immune cell populations are directly influenced by blood-brain barrier breakdown, inflammation, and gut permeability — and indirectly influenced by microbial products, gastrointestinal (GI) function, and bacterial diversity, Merchak said at the meeting, which was convened by AGA and the European Society of Neurogastroenterology and Motility.
“Many of us grew up learning that the brain is an immune-privileged site, but we’ve been establishing that this is fundamentally not true,” she said. “While the brain does have a privileged status, there are interactions with the blood, with the peripheral immune cells.”
Merchak coauthored a 2024 review in Neurotherapeutics in which she and her colleagues explained that the brain is “heavily connected with peripheral immune dynamics,” and that the gut — as the largest immune organ in the body — is a critical place for peripheral immune development, “thus influencing brain health.”
Gut microbiota interact with the brain via several mechanisms including microbiota-derived metabolites that enter circulation, direct communication via the vagus nerve, and modulation of the immune system, Merchak and her coauthors wrote. Leaky gut, they noted, can lead to an accumulation of inflammatory signals and cells that can exacerbate or induce the onset of neurodegenerative conditions.
As researchers better understand the role that GI dysfunction plays in neurodegenerative disease — as they identify microbiome signatures for predicting risk, for instance — there will be “opportunities to target the microbiome to prevent or reverse dysbiosis as a way to delay, arrest or prevent the onset and progression of neurodegenerative diseases,” they wrote.
At the GMFH meeting, Merchak described both ongoing preclinical research that is dissecting gut-brain communication, and preliminary clinical evidence for the use of gut microbiota-modulating therapies in neurodegenerative disease.
Support for a Gut-Focused Approach
Research on bile acid metabolism in multiple sclerosis (MS) and on peripheral inflammation in dementia exemplify the ongoing preclinical research uncovering the mechanisms of gut-brain communication, Merchak said.
The finding that bile acid metabolism modulates MS autoimmunity comes from research done by Merchak and a team at the University of Virginia, Charlottesville, Virginia, several years ago in which mice with experimental autoimmune encephalomyelitis (EAE) — an animal model of MS — were engineered for T cell specific knockout of the aryl hydrocarbon receptor (AHR). The AHR has been directly tied to MS, and T lymphocytes are known to play a central role in MS pathophysiology.
Blocking the activity of AHR in CD4-positive T cells significantly affected the production of bile acids and other metabolites in the microbiome — and the outcome of central nervous system autoimmunity. “Mice with high levels of bile acids, both primary and secondary, actually recovered from this EAE” and regained motor function, Merchak said at the GMFH meeting.
The potential impact of genetic manipulation on recovery was ruled out — and the role of bile acids confirmed — when, using the EAE model, gut bacteria from mice without AHR were transplanted into mice with AHR. The mice with AHR were able to recover, confirming that AHR can reprogram the gut microbiome and that “high levels of bile acid can lead to reduced autoimmunity in an MS model,” she said.
Other elements and stages of the research, which was published in PLOS Biology in 2023, showed increased apoptosis of CD4-positive immune cells in AHR-deficient mice and the ability of oral taurocholic acid — a bile acid that was especially high in mice without AHR — to reduce the severity of EAE, Merchak said.
Evidence for the role of gut and peripheral inflammation on neurodegeneration is building on numerous fronts, Merchak said. Unpublished research using spatial transcriptomics of colon biopsies from patients with inflammatory bowel disease (IBD), patients with Parkinson’s disease (PD), and neurologically healthy control individuals, for instance, showed similar cell communication patterns in patients with IBD or PD (and no history of IBD) compared with healthy control individuals.
And in research using a single-cell genomics approach and a mouse model of lipopolysaccharide (LPS)-induced system neuroinflammation, microglia were found to preferentially communicate with peripheral myeloid cells rather than other microglia after peripheral LPS exposure.
“In saline-treated mice, the microglia are talking primarily to microglia, but in LPS-treated mice, microglia spend more time communicating with monocytes and T cells,” Merchak explained. “We see communication going from inside the brain to cells coming in from the periphery.”
In another experiment, 2 months of a high-fat, high-sugar diet in mice with an engineered predisposition to frontotemporal dementia led to significant upregulation of major histocompatibility complex class II (MHC II) expression on monocytes in the brain, she said, describing unpublished research. Because MHC II handles antigen presentation in the brain, the change signals increased central-peripheral immune crosstalk and increased brain inflammation.
State of Clinical Research
On the clinical side, Merchak said studies of gut microbiome-modulating therapies are currently not longitudinal enough to accurately study neurodegenerative diseases that may develop over decades. Still, her review of the literature — part of her 2024 article — suggests there is at least some preliminary clinical evidence for the use of probiotics/prebiotics/diet and fecal microbiota transplant (FMT) in several diseases.
- Parkinson’s Disease: “There has been some evidence,” Merchak said at the meeting, “for the treatment [with probiotics, prebiotics and diet] of nonmotor symptoms — things like gastrointestinal distress and mood changes — but no real evidence that such treatments can help with the motor symptoms we see in Parkinson’s.” Over 60 patients with PD have been treated with FMT, she said, with reduced GI distress and mixed results with motor symptoms.
- Alzheimer’s and related dementias: “Diet shows promise for cognitive outcomes, but there hasn’t been much evidence for probiotics,” she said. Her review found 17 patients diagnosed with dementia who were treated with FMT, “and for many of them, maintenance of cognitive function was reported — so no further decline — which is excellent.”
- Multiple Sclerosis: “We see higher quality-of-life measures in patients getting probiotics, prebiotics, and changes in diet,” Merchak said. “Again, most of this [relates to] mood and digestion, but some studies show a slowing of neurological damage as measured by MRI.”
There are reports of 15 patients treated with FMT, and “three of these document full functional recovery,” she said, noting that longer follow-up is necessary as MS is characterized by relapsed and periods of recovery.
Merchak reported no financial disclosures.
A version of this article appeared on Medscape.com.
FROM GMFH 2025
FDA OKs Guselkumab for Crohn’s Disease
The approval marks the fourth indication for guselkumab, which was approved for moderate to severe plaque psoriasis in 2017, active psoriatic arthritis in 2020, and moderately to severely active ulcerative colitis in 2024.
Guselkumab is the first and only interleukin-23 (IL-23) inhibitor that offers both subcutaneous (SC) and intravenous (IV) induction options for CD, the company said in a news release.
“Despite the progress in the management of Crohn’s disease, many patients experience debilitating symptoms and are in need of new treatment options,” Remo Panaccione, MD, director of the Inflammatory Bowel Disease Unit at the University of Calgary, Calgary, Alberta, Canada, said in the release.
“The approval of Tremfya offers an IL-23 inhibitor that has shown robust rates of endoscopic remission with both subcutaneous and intravenous induction regimens. Importantly, the fully subcutaneous regimen offers choice and flexibility for patients and providers not available before,” said Panaccione.
The FDA nod in CD was based on positive results from three phase 3 trials evaluating guselkumab in more than 1300 patients with moderately to severely active CD who failed or were intolerant to corticosteroids, immunomodulators, or biologics.
The GRAVITI trial showed that guselkumab as SC induction and maintenance therapy was superior to placebo in clinical remission as well as endoscopic response and remission and deep remission.
Results from GALAXI 2 and GALAXI 3 showed that guselkumab was superior to ustekinumab (Stelara) on all pooled endoscopic endpoints.
Guselkumab is the only IL-23 inhibitor to demonstrate “clinical remission and endoscopic response, both at 1 year, with a fully subcutaneous induction regimen,” the company said.
The recommended SC induction dose of guselkumab is 400 mg (given as two consecutive injections of 200 mg each, dispensed in one induction pack) at weeks 0, 4 and 8. The drug is also available in a 200 mg prefilled syringe. For the IV induction option, 200 mg IV infusions are administered at weeks 0, 4, and 8.
The recommended maintenance dosage is 100 mg administered by SC injection at week 16, and every 8 weeks thereafter, or 200 mg administered by SC injection at week 12, and every 4 weeks thereafter.
Use of the lowest effective recommended dosage to maintain therapeutic response is recommended.
Full prescribing information and medication guide are available online.
A version of this article first appeared on Medscape.com.
The approval marks the fourth indication for guselkumab, which was approved for moderate to severe plaque psoriasis in 2017, active psoriatic arthritis in 2020, and moderately to severely active ulcerative colitis in 2024.
Guselkumab is the first and only interleukin-23 (IL-23) inhibitor that offers both subcutaneous (SC) and intravenous (IV) induction options for CD, the company said in a news release.
“Despite the progress in the management of Crohn’s disease, many patients experience debilitating symptoms and are in need of new treatment options,” Remo Panaccione, MD, director of the Inflammatory Bowel Disease Unit at the University of Calgary, Calgary, Alberta, Canada, said in the release.
“The approval of Tremfya offers an IL-23 inhibitor that has shown robust rates of endoscopic remission with both subcutaneous and intravenous induction regimens. Importantly, the fully subcutaneous regimen offers choice and flexibility for patients and providers not available before,” said Panaccione.
The FDA nod in CD was based on positive results from three phase 3 trials evaluating guselkumab in more than 1300 patients with moderately to severely active CD who failed or were intolerant to corticosteroids, immunomodulators, or biologics.
The GRAVITI trial showed that guselkumab as SC induction and maintenance therapy was superior to placebo in clinical remission as well as endoscopic response and remission and deep remission.
Results from GALAXI 2 and GALAXI 3 showed that guselkumab was superior to ustekinumab (Stelara) on all pooled endoscopic endpoints.
Guselkumab is the only IL-23 inhibitor to demonstrate “clinical remission and endoscopic response, both at 1 year, with a fully subcutaneous induction regimen,” the company said.
The recommended SC induction dose of guselkumab is 400 mg (given as two consecutive injections of 200 mg each, dispensed in one induction pack) at weeks 0, 4 and 8. The drug is also available in a 200 mg prefilled syringe. For the IV induction option, 200 mg IV infusions are administered at weeks 0, 4, and 8.
The recommended maintenance dosage is 100 mg administered by SC injection at week 16, and every 8 weeks thereafter, or 200 mg administered by SC injection at week 12, and every 4 weeks thereafter.
Use of the lowest effective recommended dosage to maintain therapeutic response is recommended.
Full prescribing information and medication guide are available online.
A version of this article first appeared on Medscape.com.
The approval marks the fourth indication for guselkumab, which was approved for moderate to severe plaque psoriasis in 2017, active psoriatic arthritis in 2020, and moderately to severely active ulcerative colitis in 2024.
Guselkumab is the first and only interleukin-23 (IL-23) inhibitor that offers both subcutaneous (SC) and intravenous (IV) induction options for CD, the company said in a news release.
“Despite the progress in the management of Crohn’s disease, many patients experience debilitating symptoms and are in need of new treatment options,” Remo Panaccione, MD, director of the Inflammatory Bowel Disease Unit at the University of Calgary, Calgary, Alberta, Canada, said in the release.
“The approval of Tremfya offers an IL-23 inhibitor that has shown robust rates of endoscopic remission with both subcutaneous and intravenous induction regimens. Importantly, the fully subcutaneous regimen offers choice and flexibility for patients and providers not available before,” said Panaccione.
The FDA nod in CD was based on positive results from three phase 3 trials evaluating guselkumab in more than 1300 patients with moderately to severely active CD who failed or were intolerant to corticosteroids, immunomodulators, or biologics.
The GRAVITI trial showed that guselkumab as SC induction and maintenance therapy was superior to placebo in clinical remission as well as endoscopic response and remission and deep remission.
Results from GALAXI 2 and GALAXI 3 showed that guselkumab was superior to ustekinumab (Stelara) on all pooled endoscopic endpoints.
Guselkumab is the only IL-23 inhibitor to demonstrate “clinical remission and endoscopic response, both at 1 year, with a fully subcutaneous induction regimen,” the company said.
The recommended SC induction dose of guselkumab is 400 mg (given as two consecutive injections of 200 mg each, dispensed in one induction pack) at weeks 0, 4 and 8. The drug is also available in a 200 mg prefilled syringe. For the IV induction option, 200 mg IV infusions are administered at weeks 0, 4, and 8.
The recommended maintenance dosage is 100 mg administered by SC injection at week 16, and every 8 weeks thereafter, or 200 mg administered by SC injection at week 12, and every 4 weeks thereafter.
Use of the lowest effective recommended dosage to maintain therapeutic response is recommended.
Full prescribing information and medication guide are available online.
A version of this article first appeared on Medscape.com.
Stool Test Detects Sensitivity to Food Additives
Diets in wealthier countries often include processed foods that contain additives, particularly emulsifiers. These additives are increasingly associated with the development of various diseases, including inflammatory bowel disease (IBD).
A research team led by Benoit Chassaing, PhD, research director at the French National Institute of Health and Medical Research (Inserm), focused on one such emulsifier — carboxymethylcellulose (CMC) — which is commonly found in processed baked goods, such as brioche and sandwich bread, and ice cream.
The study, published in the journal Gut, describes how the team developed a new method that uses a simple stool sample to predict an individual’s sensitivity to CMC.
Sensitivity Detection
In a previous clinical trial conducted on healthy volunteers, Chassaing and colleagues found that CMC consumption altered the gut microbiota and fecal metabolome in some healthy individuals. In mice, transplanting fecal microbiota from CMC-sensitive animals made other animals susceptible. This has led researchers to investigate the characteristics of sensitive microbiota.
To explore this, the researchers developed an in vitro microbiota model capable of replicating multiple healthy human microbiota. CMC sensitivity was tested using this model, and the findings were validated in vivo by transplanting microbiota classified as sensitive or resistant to mice. Only mice that received microbiota predicted to be CMC-sensitive developed severe colitis after consuming CMC.
Predictive Signature
Next, the team analyzed the stool metagenomes of individuals with microbiotas classified as sensitive or resistant to CMC. They identified a specific microbial signature that could predict whether a given microbiota would react negatively to emulsifiers. Using molecular analyses, this signature allows researchers to predict whether an individual’s microbiota is susceptible or resistant to CMC exposure.
For the research team, these findings open the possibility of determining whether an individual is sensitive to a particular emulsifier, allowing for personalized dietary recommendations. This is particularly relevant for patients with chronic IBD and may also help prevent these conditions in those not previously affected.
These findings could pave the way for personalized dietary recommendations, particularly for patients with chronic IBD.
To further validate these insights, the team is launching a cohort study in patients with Crohn’s to explore why some individuals are more susceptible to food additives than others.
This story was translated from Univadis France using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
Diets in wealthier countries often include processed foods that contain additives, particularly emulsifiers. These additives are increasingly associated with the development of various diseases, including inflammatory bowel disease (IBD).
A research team led by Benoit Chassaing, PhD, research director at the French National Institute of Health and Medical Research (Inserm), focused on one such emulsifier — carboxymethylcellulose (CMC) — which is commonly found in processed baked goods, such as brioche and sandwich bread, and ice cream.
The study, published in the journal Gut, describes how the team developed a new method that uses a simple stool sample to predict an individual’s sensitivity to CMC.
Sensitivity Detection
In a previous clinical trial conducted on healthy volunteers, Chassaing and colleagues found that CMC consumption altered the gut microbiota and fecal metabolome in some healthy individuals. In mice, transplanting fecal microbiota from CMC-sensitive animals made other animals susceptible. This has led researchers to investigate the characteristics of sensitive microbiota.
To explore this, the researchers developed an in vitro microbiota model capable of replicating multiple healthy human microbiota. CMC sensitivity was tested using this model, and the findings were validated in vivo by transplanting microbiota classified as sensitive or resistant to mice. Only mice that received microbiota predicted to be CMC-sensitive developed severe colitis after consuming CMC.
Predictive Signature
Next, the team analyzed the stool metagenomes of individuals with microbiotas classified as sensitive or resistant to CMC. They identified a specific microbial signature that could predict whether a given microbiota would react negatively to emulsifiers. Using molecular analyses, this signature allows researchers to predict whether an individual’s microbiota is susceptible or resistant to CMC exposure.
For the research team, these findings open the possibility of determining whether an individual is sensitive to a particular emulsifier, allowing for personalized dietary recommendations. This is particularly relevant for patients with chronic IBD and may also help prevent these conditions in those not previously affected.
These findings could pave the way for personalized dietary recommendations, particularly for patients with chronic IBD.
To further validate these insights, the team is launching a cohort study in patients with Crohn’s to explore why some individuals are more susceptible to food additives than others.
This story was translated from Univadis France using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
Diets in wealthier countries often include processed foods that contain additives, particularly emulsifiers. These additives are increasingly associated with the development of various diseases, including inflammatory bowel disease (IBD).
A research team led by Benoit Chassaing, PhD, research director at the French National Institute of Health and Medical Research (Inserm), focused on one such emulsifier — carboxymethylcellulose (CMC) — which is commonly found in processed baked goods, such as brioche and sandwich bread, and ice cream.
The study, published in the journal Gut, describes how the team developed a new method that uses a simple stool sample to predict an individual’s sensitivity to CMC.
Sensitivity Detection
In a previous clinical trial conducted on healthy volunteers, Chassaing and colleagues found that CMC consumption altered the gut microbiota and fecal metabolome in some healthy individuals. In mice, transplanting fecal microbiota from CMC-sensitive animals made other animals susceptible. This has led researchers to investigate the characteristics of sensitive microbiota.
To explore this, the researchers developed an in vitro microbiota model capable of replicating multiple healthy human microbiota. CMC sensitivity was tested using this model, and the findings were validated in vivo by transplanting microbiota classified as sensitive or resistant to mice. Only mice that received microbiota predicted to be CMC-sensitive developed severe colitis after consuming CMC.
Predictive Signature
Next, the team analyzed the stool metagenomes of individuals with microbiotas classified as sensitive or resistant to CMC. They identified a specific microbial signature that could predict whether a given microbiota would react negatively to emulsifiers. Using molecular analyses, this signature allows researchers to predict whether an individual’s microbiota is susceptible or resistant to CMC exposure.
For the research team, these findings open the possibility of determining whether an individual is sensitive to a particular emulsifier, allowing for personalized dietary recommendations. This is particularly relevant for patients with chronic IBD and may also help prevent these conditions in those not previously affected.
These findings could pave the way for personalized dietary recommendations, particularly for patients with chronic IBD.
To further validate these insights, the team is launching a cohort study in patients with Crohn’s to explore why some individuals are more susceptible to food additives than others.
This story was translated from Univadis France using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
FROM GUT
Circulating Proteins Predict Crohn’s Disease Years in Advance
The 29-protein biosignature, which was validated across multiple independent cohorts, could potentially open doors to new preclinical interventions, lead author Olle Grännö, MD, of Örebro University in Sweden, and colleagues reported.
“Predictive biomarkers of future clinical onset of active inflammatory bowel disease could detect the disease during ‘a window of opportunity’ when the immune dysregulation is potentially reversible,” the investigators wrote in Gastroenterology.
Preclinical biomarker screening has proven effective in other immune-mediated diseases, such as type 1 diabetes, where risk stratification using autoantibodies enabled early intervention that delayed disease onset, they noted.
Previous studies suggested similar potential for inflammatory bowel disease (IBD) via predictive autoantibodies and serum proteins, although the accuracy of these markers was not validated in external cohorts. The present study aimed to fill this validation gap.
First, the investigators measured 178 plasma proteins in blood samples taken from 312 individuals before they were diagnosed with IBD. Using machine learning, Dr. Grännö and colleagues compared these findings with blood-matched controls who remained free of IBD through follow-up. This process revealed the 29-protein signature.
In the same discovery cohort, the panel of 29 proteins differentiated preclinical CD cases from controls with an area under the curve (AUC) of 0.85. The signature was then validated in an independent preclinical cohort of CD patients, with an AUC of 0.87.
While accuracy increased in proximity to clinical disease onset, the model was still highly predictive up to 16 years before CD diagnosis, at which time the AUC was 0.82. The panel showed perfect performance among newly diagnosed CD patients, with an AUC of 1.0, supporting clinical relevance.
Predictive power was statistically significant but less compelling among individuals with preclinical ulcerative colitis (UC). In this IBD subgroup, AUC for identification and validation cohorts was 0.77 and 0.67, respectively, while newly diagnosed patients had an AUC of 0.95.
“In preclinical samples, downregulated (but not upregulated) proteins related to gut barrier integrity and macrophage functionality correlated with time to diagnosis of CD,” Dr. Grännö and colleagues wrote. “Contrarily, all proteins associated with preclinical UC were upregulated, and only one protein marker correlated with the time to diagnosis.”
These findings suggest that disruptions in gut barrier integrity and macrophage function precede clinical CD onset, they explained, potentially serving as an early signal of inflammation-driven intestinal damage. In contrast, the preclinical UC signature primarily involved upregulated inflammatory markers.
Dr. Grännö and colleagues also examined the influence of genetic and environmental factors by comparing preclinical IBD signatures in unrelated and related twin pairs.
The CD biosignature had an AUC of 0.89 when comparing individuals with preclinical CD to matched external (unrelated) healthy twins. Predictive ability dropped significantly (AUC = 0.58) when comparing CD cases to their own healthy twin siblings, suggesting that genetic and shared environmental factors have a “predominant influence” on protein dysregulation.
In contrast, AUC among unrelated vs related twin controls was more similar for UC, at 0.76 and 0.64, respectively, indicating “a limited impact” of genetic and environmental factors on the protein signature.
Altogether, this study reinforces the concept of a long preclinical phase in CD, and highlights the potential for early detection and intervention, according to the investigators.
“The long preclinical period in CD endorses the adoption of early preventive strategies (e.g., diet alterations and medication) to potentially attenuate disease progression and improve the natural history of CD,” they concluded.
This study was funded by the Swedish Research Council, the Swedish Foundation for Strategic Research, the Örebro University Hospital Research Foundation, and others. The investigators disclosed relationships with Pfizer, Janssen, AbbVie, and others.
Nowadays, preclinical biomarker discovery for inflammatory bowel diseases (IBD) is one of the key areas of study, aiming to identify the earliest stages of disease development and to find opportunities for early intervention. The study by Grännö and colleagues taps into this area and provides a significant advancement in the early detection of Crohn’s disease (CD) with a validated 29-plasma protein biomarker signature.
With an AUC of up to 0.87 in preclinical CD cases and even 0.82 as early as 16 years before diagnosis, these findings strongly support the notion that CD has a prolonged preclinical phase that is detectable up to many years before diagnosis. Importantly, their identified protein signatures also shed light on distinct pathophysiological mechanisms between CD and ulcerative colitis (UC), with CD characterized by early disruptions in gut barrier integrity and macrophage function, while UC was more marked by upregulated inflammatory markers.
For clinical practitioners, these findings have a strong transformative potential. Following further validation in larger cohorts and allowing clinical accessibility, preclinical biomarker screening could become a routine tool for risk stratification in at-risk individuals, such as those with a strong family history or genetic predisposition. This could enable implementation of early interventions, including dietary modifications and potentially prophylactic therapies, to delay or even prevent disease onset. Given that similar approaches have proven effective in type 1 diabetes, applying this strategy to IBD could significantly alter disease progression and patient outcomes.
Challenges remain before implementation in clinical practice could be realized. Standardized thresholds for risk assessment, cost-effectiveness analyses, and potential therapeutic strategies tailored to biomarker-positive individuals require further exploration. However, this study provides important data needed for a paradigm shift in IBD management — one that moves from reactive treatment to proactive prevention.
Arno R. Bourgonje, MD, PhD, is a postdoctoral fellow at the Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, and at the University Medical Center Groningen in Groningen, the Netherlands. He is involved in the European INTERCEPT consortium, which is focused on prediction and prevention of IBD. He reported no conflicts of interest.
Nowadays, preclinical biomarker discovery for inflammatory bowel diseases (IBD) is one of the key areas of study, aiming to identify the earliest stages of disease development and to find opportunities for early intervention. The study by Grännö and colleagues taps into this area and provides a significant advancement in the early detection of Crohn’s disease (CD) with a validated 29-plasma protein biomarker signature.
With an AUC of up to 0.87 in preclinical CD cases and even 0.82 as early as 16 years before diagnosis, these findings strongly support the notion that CD has a prolonged preclinical phase that is detectable up to many years before diagnosis. Importantly, their identified protein signatures also shed light on distinct pathophysiological mechanisms between CD and ulcerative colitis (UC), with CD characterized by early disruptions in gut barrier integrity and macrophage function, while UC was more marked by upregulated inflammatory markers.
For clinical practitioners, these findings have a strong transformative potential. Following further validation in larger cohorts and allowing clinical accessibility, preclinical biomarker screening could become a routine tool for risk stratification in at-risk individuals, such as those with a strong family history or genetic predisposition. This could enable implementation of early interventions, including dietary modifications and potentially prophylactic therapies, to delay or even prevent disease onset. Given that similar approaches have proven effective in type 1 diabetes, applying this strategy to IBD could significantly alter disease progression and patient outcomes.
Challenges remain before implementation in clinical practice could be realized. Standardized thresholds for risk assessment, cost-effectiveness analyses, and potential therapeutic strategies tailored to biomarker-positive individuals require further exploration. However, this study provides important data needed for a paradigm shift in IBD management — one that moves from reactive treatment to proactive prevention.
Arno R. Bourgonje, MD, PhD, is a postdoctoral fellow at the Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, and at the University Medical Center Groningen in Groningen, the Netherlands. He is involved in the European INTERCEPT consortium, which is focused on prediction and prevention of IBD. He reported no conflicts of interest.
Nowadays, preclinical biomarker discovery for inflammatory bowel diseases (IBD) is one of the key areas of study, aiming to identify the earliest stages of disease development and to find opportunities for early intervention. The study by Grännö and colleagues taps into this area and provides a significant advancement in the early detection of Crohn’s disease (CD) with a validated 29-plasma protein biomarker signature.
With an AUC of up to 0.87 in preclinical CD cases and even 0.82 as early as 16 years before diagnosis, these findings strongly support the notion that CD has a prolonged preclinical phase that is detectable up to many years before diagnosis. Importantly, their identified protein signatures also shed light on distinct pathophysiological mechanisms between CD and ulcerative colitis (UC), with CD characterized by early disruptions in gut barrier integrity and macrophage function, while UC was more marked by upregulated inflammatory markers.
For clinical practitioners, these findings have a strong transformative potential. Following further validation in larger cohorts and allowing clinical accessibility, preclinical biomarker screening could become a routine tool for risk stratification in at-risk individuals, such as those with a strong family history or genetic predisposition. This could enable implementation of early interventions, including dietary modifications and potentially prophylactic therapies, to delay or even prevent disease onset. Given that similar approaches have proven effective in type 1 diabetes, applying this strategy to IBD could significantly alter disease progression and patient outcomes.
Challenges remain before implementation in clinical practice could be realized. Standardized thresholds for risk assessment, cost-effectiveness analyses, and potential therapeutic strategies tailored to biomarker-positive individuals require further exploration. However, this study provides important data needed for a paradigm shift in IBD management — one that moves from reactive treatment to proactive prevention.
Arno R. Bourgonje, MD, PhD, is a postdoctoral fellow at the Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, and at the University Medical Center Groningen in Groningen, the Netherlands. He is involved in the European INTERCEPT consortium, which is focused on prediction and prevention of IBD. He reported no conflicts of interest.
The 29-protein biosignature, which was validated across multiple independent cohorts, could potentially open doors to new preclinical interventions, lead author Olle Grännö, MD, of Örebro University in Sweden, and colleagues reported.
“Predictive biomarkers of future clinical onset of active inflammatory bowel disease could detect the disease during ‘a window of opportunity’ when the immune dysregulation is potentially reversible,” the investigators wrote in Gastroenterology.
Preclinical biomarker screening has proven effective in other immune-mediated diseases, such as type 1 diabetes, where risk stratification using autoantibodies enabled early intervention that delayed disease onset, they noted.
Previous studies suggested similar potential for inflammatory bowel disease (IBD) via predictive autoantibodies and serum proteins, although the accuracy of these markers was not validated in external cohorts. The present study aimed to fill this validation gap.
First, the investigators measured 178 plasma proteins in blood samples taken from 312 individuals before they were diagnosed with IBD. Using machine learning, Dr. Grännö and colleagues compared these findings with blood-matched controls who remained free of IBD through follow-up. This process revealed the 29-protein signature.
In the same discovery cohort, the panel of 29 proteins differentiated preclinical CD cases from controls with an area under the curve (AUC) of 0.85. The signature was then validated in an independent preclinical cohort of CD patients, with an AUC of 0.87.
While accuracy increased in proximity to clinical disease onset, the model was still highly predictive up to 16 years before CD diagnosis, at which time the AUC was 0.82. The panel showed perfect performance among newly diagnosed CD patients, with an AUC of 1.0, supporting clinical relevance.
Predictive power was statistically significant but less compelling among individuals with preclinical ulcerative colitis (UC). In this IBD subgroup, AUC for identification and validation cohorts was 0.77 and 0.67, respectively, while newly diagnosed patients had an AUC of 0.95.
“In preclinical samples, downregulated (but not upregulated) proteins related to gut barrier integrity and macrophage functionality correlated with time to diagnosis of CD,” Dr. Grännö and colleagues wrote. “Contrarily, all proteins associated with preclinical UC were upregulated, and only one protein marker correlated with the time to diagnosis.”
These findings suggest that disruptions in gut barrier integrity and macrophage function precede clinical CD onset, they explained, potentially serving as an early signal of inflammation-driven intestinal damage. In contrast, the preclinical UC signature primarily involved upregulated inflammatory markers.
Dr. Grännö and colleagues also examined the influence of genetic and environmental factors by comparing preclinical IBD signatures in unrelated and related twin pairs.
The CD biosignature had an AUC of 0.89 when comparing individuals with preclinical CD to matched external (unrelated) healthy twins. Predictive ability dropped significantly (AUC = 0.58) when comparing CD cases to their own healthy twin siblings, suggesting that genetic and shared environmental factors have a “predominant influence” on protein dysregulation.
In contrast, AUC among unrelated vs related twin controls was more similar for UC, at 0.76 and 0.64, respectively, indicating “a limited impact” of genetic and environmental factors on the protein signature.
Altogether, this study reinforces the concept of a long preclinical phase in CD, and highlights the potential for early detection and intervention, according to the investigators.
“The long preclinical period in CD endorses the adoption of early preventive strategies (e.g., diet alterations and medication) to potentially attenuate disease progression and improve the natural history of CD,” they concluded.
This study was funded by the Swedish Research Council, the Swedish Foundation for Strategic Research, the Örebro University Hospital Research Foundation, and others. The investigators disclosed relationships with Pfizer, Janssen, AbbVie, and others.
The 29-protein biosignature, which was validated across multiple independent cohorts, could potentially open doors to new preclinical interventions, lead author Olle Grännö, MD, of Örebro University in Sweden, and colleagues reported.
“Predictive biomarkers of future clinical onset of active inflammatory bowel disease could detect the disease during ‘a window of opportunity’ when the immune dysregulation is potentially reversible,” the investigators wrote in Gastroenterology.
Preclinical biomarker screening has proven effective in other immune-mediated diseases, such as type 1 diabetes, where risk stratification using autoantibodies enabled early intervention that delayed disease onset, they noted.
Previous studies suggested similar potential for inflammatory bowel disease (IBD) via predictive autoantibodies and serum proteins, although the accuracy of these markers was not validated in external cohorts. The present study aimed to fill this validation gap.
First, the investigators measured 178 plasma proteins in blood samples taken from 312 individuals before they were diagnosed with IBD. Using machine learning, Dr. Grännö and colleagues compared these findings with blood-matched controls who remained free of IBD through follow-up. This process revealed the 29-protein signature.
In the same discovery cohort, the panel of 29 proteins differentiated preclinical CD cases from controls with an area under the curve (AUC) of 0.85. The signature was then validated in an independent preclinical cohort of CD patients, with an AUC of 0.87.
While accuracy increased in proximity to clinical disease onset, the model was still highly predictive up to 16 years before CD diagnosis, at which time the AUC was 0.82. The panel showed perfect performance among newly diagnosed CD patients, with an AUC of 1.0, supporting clinical relevance.
Predictive power was statistically significant but less compelling among individuals with preclinical ulcerative colitis (UC). In this IBD subgroup, AUC for identification and validation cohorts was 0.77 and 0.67, respectively, while newly diagnosed patients had an AUC of 0.95.
“In preclinical samples, downregulated (but not upregulated) proteins related to gut barrier integrity and macrophage functionality correlated with time to diagnosis of CD,” Dr. Grännö and colleagues wrote. “Contrarily, all proteins associated with preclinical UC were upregulated, and only one protein marker correlated with the time to diagnosis.”
These findings suggest that disruptions in gut barrier integrity and macrophage function precede clinical CD onset, they explained, potentially serving as an early signal of inflammation-driven intestinal damage. In contrast, the preclinical UC signature primarily involved upregulated inflammatory markers.
Dr. Grännö and colleagues also examined the influence of genetic and environmental factors by comparing preclinical IBD signatures in unrelated and related twin pairs.
The CD biosignature had an AUC of 0.89 when comparing individuals with preclinical CD to matched external (unrelated) healthy twins. Predictive ability dropped significantly (AUC = 0.58) when comparing CD cases to their own healthy twin siblings, suggesting that genetic and shared environmental factors have a “predominant influence” on protein dysregulation.
In contrast, AUC among unrelated vs related twin controls was more similar for UC, at 0.76 and 0.64, respectively, indicating “a limited impact” of genetic and environmental factors on the protein signature.
Altogether, this study reinforces the concept of a long preclinical phase in CD, and highlights the potential for early detection and intervention, according to the investigators.
“The long preclinical period in CD endorses the adoption of early preventive strategies (e.g., diet alterations and medication) to potentially attenuate disease progression and improve the natural history of CD,” they concluded.
This study was funded by the Swedish Research Council, the Swedish Foundation for Strategic Research, the Örebro University Hospital Research Foundation, and others. The investigators disclosed relationships with Pfizer, Janssen, AbbVie, and others.
FROM GASTROENTEROLOGY
Vedolizumab Beats Infliximab as Second-Line Therapy for Ulcerative Colitis
BERLIN — suggests EFFICACI, the first trial directly comparing second-line advanced therapies in patients with the disease.
Vedolizumab was superior to infliximab to achieving steroid-free clinical remission at week 14 in patients who had failed on a first-line subcutaneous anti–tumor necrosis factor (anti-TNF) therapy, said study presenter Guillaume Bouguen, MD, PhD, of the gastroenterology gepartment, CHU Rennes – Pontchaillou Hospital, France.
The drug also outperformed infliximab in the induction of endoscopic improvement, and its safety outcomes were “consistent with the known profile of both drugs in previous trials,” Bouguen said.
The research was presented at the European Crohn’s and Colitis Organisation 2025 Congress.
The study reports only short-term outcomes, so it “remains unclear whether vedolizumab’s advantage is sustained over time or whether infliximab may catch up in effectiveness,” Tauseef Ali, MD, AGAF, executive medical director, SSM Health St. Anthony Digestive Care, Crohn’s and Colitis Center, Oklahoma City, said in an interview.
Bouguen noted that the trial was unblinded at week 14 and that patients were followed up to week 54, data for which will be presented in the near future.
Head-to-Head Trial
Treating ulcerative colitis beyond the first line of therapy is “becoming challenging” because there are several therapeutic classes and drugs to choose from but no strong evidence to support physician decision-making, Bouguen said.
No head-to-head trials for second-line advanced therapies for UC had been performed, he said. So Bouguen and colleagues conducted a randomized, double-blind trial to determine whether vedolizumab, an integrin receptor agonist, is superior to infliximab, a TNF antagonist, in ulcerative colitis patients who had failed a first-line subcutaneous TNF antagonist.
They enrolled patients with moderate to severe disease, defined by a total Mayo score ≥ 6, despite at least 12 weeks of treatment with the TNF antagonists golimumab (Simponi) or adalimumab (Humira and others), from 24 centers across France.
Participants were randomly assigned to intravenous 300 mg vedolizumab or 5 mg/kg infliximab. Clinical biological assessments performed at baseline and at weeks 2 and 6. The primary endpoint was steroid-free clinical remission (Mayo score ≤ 2) at week 14.
Of 165 patients assessed for eligibility, 78 were randomly assigned to vedolizumab and 73 to infliximab, of whom 77 and 70 and patients, respectively, were available for assessment at week 14. Approximately 40% of the participants were women, and the average age was almost 40 years.
The mean total Mayo score at baseline was comparable between the two groups (9.0 vedolizumab; 8.7 infliximab). The majority in both groups had previously been treated with adalimumab, and almost 60% had experienced a loss of response to therapy.
Steroid-free clinical remission at week 14 was achieved by 34.6% of patients treated with vedolizumab vs 19.2% of those given infliximab (P = .033).
Endoscopic remission at week 14 was achieved by 19.5% of patients in the vedolizumab group vs 8.3% of those treated with infliximab (P = .0507), while endoscopic improvement was seen in 46.8% and 29.2% of patients, respectively (P = .0273).
There were no statistically significant differences between the two treatment groups in rates of clinical response or mean C-reactive protein (CRP) levels between baseline and week 14, and there was no significant difference in fecal calprotectin levels at week 14.
Interestingly, Bouguen said that, from parameters such as age, sex, Mayo score, CRP levels, and concomitant immunosuppressant use, there were no significant predictors of clinical remission.
The overall incidence of adverse events, including respiratory tract and Clostridioides difficile infections, was comparable between the vedolizumab and infliximab groups, although patients receiving infliximab had higher rates of disease worsening and infusion reactions.
Questions Remain
Study coinvestigator Matthieu Allez, MD, PhD, head of the gastroenterology department, Hôpital Saint-Louis, Assistance Publique Hopitaux de Paris, said in an interview that he was surprised by the findings.
“I think infliximab is a much better drug than vedolizumab,” considering the rate of immunosuppressant combination therapy that is administered in ulcerative colitis, said Allez, who was the session’s co-chair.
This is a “key aspect” as “you can give more” of such therapy to patients receiving infliximab, “but, in fact, it seems like they do better” with vedolizumab, Allez said.
Ali said that the trial “addresses a critical gap in the treatment of ulcerative colitis: Whether switching within the anti-TNF class or swapping to vedolizumab is more effective after failure of a first subcutaneous anti-TNF.”
“This question has real-world clinical relevance, as gastroenterologists often face this decision,” he added.
Ali, who was not involved in the study, said that even though the results “suggest that vedolizumab may be a more effective option than infliximab in this patient population” and there were no major safety concerns with either drug, “one must exercise caution in interpreting and applying the results to clinical practice.”
Moreover, the lack of statistically significant clinical response rates between the drugs “raises questions about whether the primary endpoint difference is clinically meaningful over the long term,” he said.
The study was conducted in only one country, thus potentially limiting its generalizability, Ali noted, and it included only patients who had failed on subcutaneous, not intravenous, anti-TNF therapy. There was also a lack of biomarker stratification, “making it unclear which patients would benefit most from switching vs swapping strategies,” he added.
“While vedolizumab may be preferable, many other factors,” such as drug serum levels, immunogenicity, urgency of response, access, and cost, “should guide decision-making,” Ali said.
The study was funded by the French national research program, with additional funding from Takeda. Bouguen declared relationships with Abbvie, Janssen, Lilly, Takeda, Celltrion, Sandoz, Galapagos, Tillotts, and Amgen. No other disclosures were reported.
A version of this article appeared on Medscape.com.
BERLIN — suggests EFFICACI, the first trial directly comparing second-line advanced therapies in patients with the disease.
Vedolizumab was superior to infliximab to achieving steroid-free clinical remission at week 14 in patients who had failed on a first-line subcutaneous anti–tumor necrosis factor (anti-TNF) therapy, said study presenter Guillaume Bouguen, MD, PhD, of the gastroenterology gepartment, CHU Rennes – Pontchaillou Hospital, France.
The drug also outperformed infliximab in the induction of endoscopic improvement, and its safety outcomes were “consistent with the known profile of both drugs in previous trials,” Bouguen said.
The research was presented at the European Crohn’s and Colitis Organisation 2025 Congress.
The study reports only short-term outcomes, so it “remains unclear whether vedolizumab’s advantage is sustained over time or whether infliximab may catch up in effectiveness,” Tauseef Ali, MD, AGAF, executive medical director, SSM Health St. Anthony Digestive Care, Crohn’s and Colitis Center, Oklahoma City, said in an interview.
Bouguen noted that the trial was unblinded at week 14 and that patients were followed up to week 54, data for which will be presented in the near future.
Head-to-Head Trial
Treating ulcerative colitis beyond the first line of therapy is “becoming challenging” because there are several therapeutic classes and drugs to choose from but no strong evidence to support physician decision-making, Bouguen said.
No head-to-head trials for second-line advanced therapies for UC had been performed, he said. So Bouguen and colleagues conducted a randomized, double-blind trial to determine whether vedolizumab, an integrin receptor agonist, is superior to infliximab, a TNF antagonist, in ulcerative colitis patients who had failed a first-line subcutaneous TNF antagonist.
They enrolled patients with moderate to severe disease, defined by a total Mayo score ≥ 6, despite at least 12 weeks of treatment with the TNF antagonists golimumab (Simponi) or adalimumab (Humira and others), from 24 centers across France.
Participants were randomly assigned to intravenous 300 mg vedolizumab or 5 mg/kg infliximab. Clinical biological assessments performed at baseline and at weeks 2 and 6. The primary endpoint was steroid-free clinical remission (Mayo score ≤ 2) at week 14.
Of 165 patients assessed for eligibility, 78 were randomly assigned to vedolizumab and 73 to infliximab, of whom 77 and 70 and patients, respectively, were available for assessment at week 14. Approximately 40% of the participants were women, and the average age was almost 40 years.
The mean total Mayo score at baseline was comparable between the two groups (9.0 vedolizumab; 8.7 infliximab). The majority in both groups had previously been treated with adalimumab, and almost 60% had experienced a loss of response to therapy.
Steroid-free clinical remission at week 14 was achieved by 34.6% of patients treated with vedolizumab vs 19.2% of those given infliximab (P = .033).
Endoscopic remission at week 14 was achieved by 19.5% of patients in the vedolizumab group vs 8.3% of those treated with infliximab (P = .0507), while endoscopic improvement was seen in 46.8% and 29.2% of patients, respectively (P = .0273).
There were no statistically significant differences between the two treatment groups in rates of clinical response or mean C-reactive protein (CRP) levels between baseline and week 14, and there was no significant difference in fecal calprotectin levels at week 14.
Interestingly, Bouguen said that, from parameters such as age, sex, Mayo score, CRP levels, and concomitant immunosuppressant use, there were no significant predictors of clinical remission.
The overall incidence of adverse events, including respiratory tract and Clostridioides difficile infections, was comparable between the vedolizumab and infliximab groups, although patients receiving infliximab had higher rates of disease worsening and infusion reactions.
Questions Remain
Study coinvestigator Matthieu Allez, MD, PhD, head of the gastroenterology department, Hôpital Saint-Louis, Assistance Publique Hopitaux de Paris, said in an interview that he was surprised by the findings.
“I think infliximab is a much better drug than vedolizumab,” considering the rate of immunosuppressant combination therapy that is administered in ulcerative colitis, said Allez, who was the session’s co-chair.
This is a “key aspect” as “you can give more” of such therapy to patients receiving infliximab, “but, in fact, it seems like they do better” with vedolizumab, Allez said.
Ali said that the trial “addresses a critical gap in the treatment of ulcerative colitis: Whether switching within the anti-TNF class or swapping to vedolizumab is more effective after failure of a first subcutaneous anti-TNF.”
“This question has real-world clinical relevance, as gastroenterologists often face this decision,” he added.
Ali, who was not involved in the study, said that even though the results “suggest that vedolizumab may be a more effective option than infliximab in this patient population” and there were no major safety concerns with either drug, “one must exercise caution in interpreting and applying the results to clinical practice.”
Moreover, the lack of statistically significant clinical response rates between the drugs “raises questions about whether the primary endpoint difference is clinically meaningful over the long term,” he said.
The study was conducted in only one country, thus potentially limiting its generalizability, Ali noted, and it included only patients who had failed on subcutaneous, not intravenous, anti-TNF therapy. There was also a lack of biomarker stratification, “making it unclear which patients would benefit most from switching vs swapping strategies,” he added.
“While vedolizumab may be preferable, many other factors,” such as drug serum levels, immunogenicity, urgency of response, access, and cost, “should guide decision-making,” Ali said.
The study was funded by the French national research program, with additional funding from Takeda. Bouguen declared relationships with Abbvie, Janssen, Lilly, Takeda, Celltrion, Sandoz, Galapagos, Tillotts, and Amgen. No other disclosures were reported.
A version of this article appeared on Medscape.com.
BERLIN — suggests EFFICACI, the first trial directly comparing second-line advanced therapies in patients with the disease.
Vedolizumab was superior to infliximab to achieving steroid-free clinical remission at week 14 in patients who had failed on a first-line subcutaneous anti–tumor necrosis factor (anti-TNF) therapy, said study presenter Guillaume Bouguen, MD, PhD, of the gastroenterology gepartment, CHU Rennes – Pontchaillou Hospital, France.
The drug also outperformed infliximab in the induction of endoscopic improvement, and its safety outcomes were “consistent with the known profile of both drugs in previous trials,” Bouguen said.
The research was presented at the European Crohn’s and Colitis Organisation 2025 Congress.
The study reports only short-term outcomes, so it “remains unclear whether vedolizumab’s advantage is sustained over time or whether infliximab may catch up in effectiveness,” Tauseef Ali, MD, AGAF, executive medical director, SSM Health St. Anthony Digestive Care, Crohn’s and Colitis Center, Oklahoma City, said in an interview.
Bouguen noted that the trial was unblinded at week 14 and that patients were followed up to week 54, data for which will be presented in the near future.
Head-to-Head Trial
Treating ulcerative colitis beyond the first line of therapy is “becoming challenging” because there are several therapeutic classes and drugs to choose from but no strong evidence to support physician decision-making, Bouguen said.
No head-to-head trials for second-line advanced therapies for UC had been performed, he said. So Bouguen and colleagues conducted a randomized, double-blind trial to determine whether vedolizumab, an integrin receptor agonist, is superior to infliximab, a TNF antagonist, in ulcerative colitis patients who had failed a first-line subcutaneous TNF antagonist.
They enrolled patients with moderate to severe disease, defined by a total Mayo score ≥ 6, despite at least 12 weeks of treatment with the TNF antagonists golimumab (Simponi) or adalimumab (Humira and others), from 24 centers across France.
Participants were randomly assigned to intravenous 300 mg vedolizumab or 5 mg/kg infliximab. Clinical biological assessments performed at baseline and at weeks 2 and 6. The primary endpoint was steroid-free clinical remission (Mayo score ≤ 2) at week 14.
Of 165 patients assessed for eligibility, 78 were randomly assigned to vedolizumab and 73 to infliximab, of whom 77 and 70 and patients, respectively, were available for assessment at week 14. Approximately 40% of the participants were women, and the average age was almost 40 years.
The mean total Mayo score at baseline was comparable between the two groups (9.0 vedolizumab; 8.7 infliximab). The majority in both groups had previously been treated with adalimumab, and almost 60% had experienced a loss of response to therapy.
Steroid-free clinical remission at week 14 was achieved by 34.6% of patients treated with vedolizumab vs 19.2% of those given infliximab (P = .033).
Endoscopic remission at week 14 was achieved by 19.5% of patients in the vedolizumab group vs 8.3% of those treated with infliximab (P = .0507), while endoscopic improvement was seen in 46.8% and 29.2% of patients, respectively (P = .0273).
There were no statistically significant differences between the two treatment groups in rates of clinical response or mean C-reactive protein (CRP) levels between baseline and week 14, and there was no significant difference in fecal calprotectin levels at week 14.
Interestingly, Bouguen said that, from parameters such as age, sex, Mayo score, CRP levels, and concomitant immunosuppressant use, there were no significant predictors of clinical remission.
The overall incidence of adverse events, including respiratory tract and Clostridioides difficile infections, was comparable between the vedolizumab and infliximab groups, although patients receiving infliximab had higher rates of disease worsening and infusion reactions.
Questions Remain
Study coinvestigator Matthieu Allez, MD, PhD, head of the gastroenterology department, Hôpital Saint-Louis, Assistance Publique Hopitaux de Paris, said in an interview that he was surprised by the findings.
“I think infliximab is a much better drug than vedolizumab,” considering the rate of immunosuppressant combination therapy that is administered in ulcerative colitis, said Allez, who was the session’s co-chair.
This is a “key aspect” as “you can give more” of such therapy to patients receiving infliximab, “but, in fact, it seems like they do better” with vedolizumab, Allez said.
Ali said that the trial “addresses a critical gap in the treatment of ulcerative colitis: Whether switching within the anti-TNF class or swapping to vedolizumab is more effective after failure of a first subcutaneous anti-TNF.”
“This question has real-world clinical relevance, as gastroenterologists often face this decision,” he added.
Ali, who was not involved in the study, said that even though the results “suggest that vedolizumab may be a more effective option than infliximab in this patient population” and there were no major safety concerns with either drug, “one must exercise caution in interpreting and applying the results to clinical practice.”
Moreover, the lack of statistically significant clinical response rates between the drugs “raises questions about whether the primary endpoint difference is clinically meaningful over the long term,” he said.
The study was conducted in only one country, thus potentially limiting its generalizability, Ali noted, and it included only patients who had failed on subcutaneous, not intravenous, anti-TNF therapy. There was also a lack of biomarker stratification, “making it unclear which patients would benefit most from switching vs swapping strategies,” he added.
“While vedolizumab may be preferable, many other factors,” such as drug serum levels, immunogenicity, urgency of response, access, and cost, “should guide decision-making,” Ali said.
The study was funded by the French national research program, with additional funding from Takeda. Bouguen declared relationships with Abbvie, Janssen, Lilly, Takeda, Celltrion, Sandoz, Galapagos, Tillotts, and Amgen. No other disclosures were reported.
A version of this article appeared on Medscape.com.
FROM ECCO 2025
Subcutaneous Guselkumab Proves Efficacious for IBD in Two Studies: ASTRO and GRAVITI
BERLIN — according to results from the phase 3, randomized, double-blind, placebo-controlled ASTRO study.
Importantly, the study also showed that subcutaneous induction is consistent with intravenous (IV) induction of guselkumab in UC.
“The flexibility of a fully subcutaneous treatment regimen would be a welcome option for many patients, especially those with busy and active lifestyles,” said study lead Laurent Peyrin-Biroulet, MD, head of the inflammatory bowel disease (IBD) unit at University Hospital of Nancy, France.
Peyrin-Biroulet presented the results at European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.
“I think it’s an evolution and improvement in terms of IBD management,” he said. “We are happy that our patients will have the choice.”
Guselkumab is a selective dual-acting interleukin (IL)–23p19 subunit inhibitor that potently blocks IL-23 and binds to CD64, a receptor on cells that produce IL-23, and is the only full subcutaneous IL-23 available. The drug is approved in some countries, including the United States, for UC.
The ASTRO Study
Building on data from the QUASAR studies, which showed the efficacy of induction of IV guselkumab and subcutaneous maintenance in patients with UC, the ASTRO study randomly assigned 418 patients with moderately to severely active UC to receive either induction with 400 mg subcutaneous guselkumab at weeks 0, 4, and 8 or placebo.
After induction, the treatment group either received a maintenance dose of 200 mg subcutaneous guselkumab at week 12 and then every 4 weeks or 100 mg every 8 weeks (starting week 16).
All patients had an inadequate response or intolerance to conventional therapy. Around 60% were naive to biologics, Janus kinase (JAK) inhibitors, or sphingosine-1-phosphate receptor modulators (S1Ps).
Clinical remission at week 12 — the primary endpoint — was achieved by 27.6% of all patients treated with guselkumab compared with 6.5% of patients on placebo (P < .001).
“These results are in line with the QUASAR data,” in which clinical remission was 22.6% with IV guselkumab at 12 weeks, noted Peyrin-Biroulet.
The researchers also divided the results by prespecified subgroups based on previous treatments.
Clinical remission was achieved at week 12 by 36% of patients naive to biologics, JAK inhibitors, or S1Ps in the guselkumab group and by 8.9% of these patients in the placebo group (P < .001). Among patients who had previously received biologics, JAK inhibitors, or S1Ps, 16.1% of those in the guselkumab group achieved clinical remission compared with 3.6% of those in the placebo group (P = .005).
“In terms of symptomatic remission at week 12, the difference between the overall guselkumab result and placebo was 30%,” reported Peyrin-Biroulet.
Clinical response — defined as a decrease in the modified Mayo score by ≥ 30% and ≥ 2 points, with either a ≥ 1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1 — was 65.6% in the guselkumab group compared with 34.5% in the placebo group (P < .001).
Among patients naive to biologics, JAK inhibitors, or S1Ps, clinical response was 71.3% in the guselkumab group, compared with 41.8% in the placebo group (P < .001). Among those who had previously received biologics, JAK inhibitors, or S1Ps, it was 57.1% in the guselkumab group, compared with 25.0% in the placebo group (P < .001).
Turning to endoscopic improvement (ie, an endoscopic subscore of 0 or 1 with no friability), 37.3% of those in the guselkumab group overall, compared with 12.9% of those in the placebo group who achieved this endpoint (P < .001).
“This is a treatment effect of over 20%,” said Peyrin-Biroulet. “We know that when it is over 20%, it is considered game changer.”
In patients naive to biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 45.7% with guselkumab vs 17.7% with placebo. In those who had previously received biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 24.1% with guselkumab vs 7.1% with placebo. Both were statistically significant.
The safety of subcutaneous induction therapy was consistent with the well-characterized and favorable safety profile of guselkumab in approved indications.
The GRAVITI Study
In the phase 3, randomized, double-blind, placebo-controlled GRAVITI study, also presented at ECCO 2025 Congress, researchers evaluated the efficacy and safety of induction with subcutaneous guselkumab followed by subcutaneous maintenance compared with placebo in patients with moderately to severely active Crohn’s disease.
The GRAVITI study followed the same induction and maintenance dosage and treatment intervals as the ASTRO study.
In addition, the patients randomly assigned to placebo were able to receive subcutaneous guselkumab (400 mg every 4 weeks followed by 100 mg every 8 weeks) if rescue criteria were met at week 16.
The co-primary endpoints were clinical remission and endoscopic response at week 12.
Ailsa Hart, MD, director, IBD Research, and consultant gastroenterologist, St. Mark’s Hospital and Imperial College, both in London, reported the 12-week and 48-week results, which were initially presented at the American College of Gastroenterology (ACG) meeting in October 2024.
At week 12, 56.1% of patients who received guselkumab achieved clinical remission, compared with 21.4% of patients who received placebo. Endoscopic response was achieved in 41.3% of patients treated with guselkumab compared with 21.4% in the placebo group.
Regarding the 48-week results, Hart noted that the rate of clinical remission was more than three times higher with both maintenance doses of guselkumab at 66.1% (200 mg) and 60.0% (100 mg) vs 17.1% with placebo.
Endoscopic response at 48 weeks was achieved in 51.3% of patients on the 200-mg maintenance dose and in 44.3% on the 100-mg maintenance dose, compared with 6.8% of patients on placebo.
In addition, endoscopic remission was achieved in 38.3% of patients in the 200-mg guselkumab group and in 30.4% in the 100-mg guselkumab group, compared with 6.0% in the placebo group.
Safety findings were consistent with the known safety profile of guselkumab in approved indications and other studies in IBD.
“These results complement the GALAXI data and demonstrate that both IV and subcutaneous guselkumab induction are efficacious and therapeutic in Crohn’s disease,” Hart said. Furthermore, data from the ASTRO study demonstrated similar data in the UC population.
As clinicians, this gives us flexibility in how we treat our patients; although, the rationale for choosing subcutaneous or IV is likely to be pragmatic, Hart said.
Additionally, the flexibility of the maintenance therapy, that is, 200 mg subcutaneous guselkumab every 4 weeks or 100 mg every 8 weeks, “is expected to positively affect several parameters of therapy, including increased compliance, hospital avoidance, and better safety profiling,” comoderator Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, said in an interview.
It appears that multiple options will be offered to patients regarding treatment with guselkumab for patients with Crohn’s disease, Bamias said. “Interestingly, a similar multiplicity of options has also been shown for ulcerative colitis, through the QUASAR and ASTRO studies.”
Peyrin-Biroulet declared receiving grants and other/support travel from multiple companies. Hart declared receiving grants and personal fees from multiple companies. Bamias declared receiving grants and personal fees/honoraria as an advisor/lecturer from multiple companies.
A version of this article appeared on Medscape.com.
BERLIN — according to results from the phase 3, randomized, double-blind, placebo-controlled ASTRO study.
Importantly, the study also showed that subcutaneous induction is consistent with intravenous (IV) induction of guselkumab in UC.
“The flexibility of a fully subcutaneous treatment regimen would be a welcome option for many patients, especially those with busy and active lifestyles,” said study lead Laurent Peyrin-Biroulet, MD, head of the inflammatory bowel disease (IBD) unit at University Hospital of Nancy, France.
Peyrin-Biroulet presented the results at European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.
“I think it’s an evolution and improvement in terms of IBD management,” he said. “We are happy that our patients will have the choice.”
Guselkumab is a selective dual-acting interleukin (IL)–23p19 subunit inhibitor that potently blocks IL-23 and binds to CD64, a receptor on cells that produce IL-23, and is the only full subcutaneous IL-23 available. The drug is approved in some countries, including the United States, for UC.
The ASTRO Study
Building on data from the QUASAR studies, which showed the efficacy of induction of IV guselkumab and subcutaneous maintenance in patients with UC, the ASTRO study randomly assigned 418 patients with moderately to severely active UC to receive either induction with 400 mg subcutaneous guselkumab at weeks 0, 4, and 8 or placebo.
After induction, the treatment group either received a maintenance dose of 200 mg subcutaneous guselkumab at week 12 and then every 4 weeks or 100 mg every 8 weeks (starting week 16).
All patients had an inadequate response or intolerance to conventional therapy. Around 60% were naive to biologics, Janus kinase (JAK) inhibitors, or sphingosine-1-phosphate receptor modulators (S1Ps).
Clinical remission at week 12 — the primary endpoint — was achieved by 27.6% of all patients treated with guselkumab compared with 6.5% of patients on placebo (P < .001).
“These results are in line with the QUASAR data,” in which clinical remission was 22.6% with IV guselkumab at 12 weeks, noted Peyrin-Biroulet.
The researchers also divided the results by prespecified subgroups based on previous treatments.
Clinical remission was achieved at week 12 by 36% of patients naive to biologics, JAK inhibitors, or S1Ps in the guselkumab group and by 8.9% of these patients in the placebo group (P < .001). Among patients who had previously received biologics, JAK inhibitors, or S1Ps, 16.1% of those in the guselkumab group achieved clinical remission compared with 3.6% of those in the placebo group (P = .005).
“In terms of symptomatic remission at week 12, the difference between the overall guselkumab result and placebo was 30%,” reported Peyrin-Biroulet.
Clinical response — defined as a decrease in the modified Mayo score by ≥ 30% and ≥ 2 points, with either a ≥ 1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1 — was 65.6% in the guselkumab group compared with 34.5% in the placebo group (P < .001).
Among patients naive to biologics, JAK inhibitors, or S1Ps, clinical response was 71.3% in the guselkumab group, compared with 41.8% in the placebo group (P < .001). Among those who had previously received biologics, JAK inhibitors, or S1Ps, it was 57.1% in the guselkumab group, compared with 25.0% in the placebo group (P < .001).
Turning to endoscopic improvement (ie, an endoscopic subscore of 0 or 1 with no friability), 37.3% of those in the guselkumab group overall, compared with 12.9% of those in the placebo group who achieved this endpoint (P < .001).
“This is a treatment effect of over 20%,” said Peyrin-Biroulet. “We know that when it is over 20%, it is considered game changer.”
In patients naive to biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 45.7% with guselkumab vs 17.7% with placebo. In those who had previously received biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 24.1% with guselkumab vs 7.1% with placebo. Both were statistically significant.
The safety of subcutaneous induction therapy was consistent with the well-characterized and favorable safety profile of guselkumab in approved indications.
The GRAVITI Study
In the phase 3, randomized, double-blind, placebo-controlled GRAVITI study, also presented at ECCO 2025 Congress, researchers evaluated the efficacy and safety of induction with subcutaneous guselkumab followed by subcutaneous maintenance compared with placebo in patients with moderately to severely active Crohn’s disease.
The GRAVITI study followed the same induction and maintenance dosage and treatment intervals as the ASTRO study.
In addition, the patients randomly assigned to placebo were able to receive subcutaneous guselkumab (400 mg every 4 weeks followed by 100 mg every 8 weeks) if rescue criteria were met at week 16.
The co-primary endpoints were clinical remission and endoscopic response at week 12.
Ailsa Hart, MD, director, IBD Research, and consultant gastroenterologist, St. Mark’s Hospital and Imperial College, both in London, reported the 12-week and 48-week results, which were initially presented at the American College of Gastroenterology (ACG) meeting in October 2024.
At week 12, 56.1% of patients who received guselkumab achieved clinical remission, compared with 21.4% of patients who received placebo. Endoscopic response was achieved in 41.3% of patients treated with guselkumab compared with 21.4% in the placebo group.
Regarding the 48-week results, Hart noted that the rate of clinical remission was more than three times higher with both maintenance doses of guselkumab at 66.1% (200 mg) and 60.0% (100 mg) vs 17.1% with placebo.
Endoscopic response at 48 weeks was achieved in 51.3% of patients on the 200-mg maintenance dose and in 44.3% on the 100-mg maintenance dose, compared with 6.8% of patients on placebo.
In addition, endoscopic remission was achieved in 38.3% of patients in the 200-mg guselkumab group and in 30.4% in the 100-mg guselkumab group, compared with 6.0% in the placebo group.
Safety findings were consistent with the known safety profile of guselkumab in approved indications and other studies in IBD.
“These results complement the GALAXI data and demonstrate that both IV and subcutaneous guselkumab induction are efficacious and therapeutic in Crohn’s disease,” Hart said. Furthermore, data from the ASTRO study demonstrated similar data in the UC population.
As clinicians, this gives us flexibility in how we treat our patients; although, the rationale for choosing subcutaneous or IV is likely to be pragmatic, Hart said.
Additionally, the flexibility of the maintenance therapy, that is, 200 mg subcutaneous guselkumab every 4 weeks or 100 mg every 8 weeks, “is expected to positively affect several parameters of therapy, including increased compliance, hospital avoidance, and better safety profiling,” comoderator Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, said in an interview.
It appears that multiple options will be offered to patients regarding treatment with guselkumab for patients with Crohn’s disease, Bamias said. “Interestingly, a similar multiplicity of options has also been shown for ulcerative colitis, through the QUASAR and ASTRO studies.”
Peyrin-Biroulet declared receiving grants and other/support travel from multiple companies. Hart declared receiving grants and personal fees from multiple companies. Bamias declared receiving grants and personal fees/honoraria as an advisor/lecturer from multiple companies.
A version of this article appeared on Medscape.com.
BERLIN — according to results from the phase 3, randomized, double-blind, placebo-controlled ASTRO study.
Importantly, the study also showed that subcutaneous induction is consistent with intravenous (IV) induction of guselkumab in UC.
“The flexibility of a fully subcutaneous treatment regimen would be a welcome option for many patients, especially those with busy and active lifestyles,” said study lead Laurent Peyrin-Biroulet, MD, head of the inflammatory bowel disease (IBD) unit at University Hospital of Nancy, France.
Peyrin-Biroulet presented the results at European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.
“I think it’s an evolution and improvement in terms of IBD management,” he said. “We are happy that our patients will have the choice.”
Guselkumab is a selective dual-acting interleukin (IL)–23p19 subunit inhibitor that potently blocks IL-23 and binds to CD64, a receptor on cells that produce IL-23, and is the only full subcutaneous IL-23 available. The drug is approved in some countries, including the United States, for UC.
The ASTRO Study
Building on data from the QUASAR studies, which showed the efficacy of induction of IV guselkumab and subcutaneous maintenance in patients with UC, the ASTRO study randomly assigned 418 patients with moderately to severely active UC to receive either induction with 400 mg subcutaneous guselkumab at weeks 0, 4, and 8 or placebo.
After induction, the treatment group either received a maintenance dose of 200 mg subcutaneous guselkumab at week 12 and then every 4 weeks or 100 mg every 8 weeks (starting week 16).
All patients had an inadequate response or intolerance to conventional therapy. Around 60% were naive to biologics, Janus kinase (JAK) inhibitors, or sphingosine-1-phosphate receptor modulators (S1Ps).
Clinical remission at week 12 — the primary endpoint — was achieved by 27.6% of all patients treated with guselkumab compared with 6.5% of patients on placebo (P < .001).
“These results are in line with the QUASAR data,” in which clinical remission was 22.6% with IV guselkumab at 12 weeks, noted Peyrin-Biroulet.
The researchers also divided the results by prespecified subgroups based on previous treatments.
Clinical remission was achieved at week 12 by 36% of patients naive to biologics, JAK inhibitors, or S1Ps in the guselkumab group and by 8.9% of these patients in the placebo group (P < .001). Among patients who had previously received biologics, JAK inhibitors, or S1Ps, 16.1% of those in the guselkumab group achieved clinical remission compared with 3.6% of those in the placebo group (P = .005).
“In terms of symptomatic remission at week 12, the difference between the overall guselkumab result and placebo was 30%,” reported Peyrin-Biroulet.
Clinical response — defined as a decrease in the modified Mayo score by ≥ 30% and ≥ 2 points, with either a ≥ 1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1 — was 65.6% in the guselkumab group compared with 34.5% in the placebo group (P < .001).
Among patients naive to biologics, JAK inhibitors, or S1Ps, clinical response was 71.3% in the guselkumab group, compared with 41.8% in the placebo group (P < .001). Among those who had previously received biologics, JAK inhibitors, or S1Ps, it was 57.1% in the guselkumab group, compared with 25.0% in the placebo group (P < .001).
Turning to endoscopic improvement (ie, an endoscopic subscore of 0 or 1 with no friability), 37.3% of those in the guselkumab group overall, compared with 12.9% of those in the placebo group who achieved this endpoint (P < .001).
“This is a treatment effect of over 20%,” said Peyrin-Biroulet. “We know that when it is over 20%, it is considered game changer.”
In patients naive to biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 45.7% with guselkumab vs 17.7% with placebo. In those who had previously received biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 24.1% with guselkumab vs 7.1% with placebo. Both were statistically significant.
The safety of subcutaneous induction therapy was consistent with the well-characterized and favorable safety profile of guselkumab in approved indications.
The GRAVITI Study
In the phase 3, randomized, double-blind, placebo-controlled GRAVITI study, also presented at ECCO 2025 Congress, researchers evaluated the efficacy and safety of induction with subcutaneous guselkumab followed by subcutaneous maintenance compared with placebo in patients with moderately to severely active Crohn’s disease.
The GRAVITI study followed the same induction and maintenance dosage and treatment intervals as the ASTRO study.
In addition, the patients randomly assigned to placebo were able to receive subcutaneous guselkumab (400 mg every 4 weeks followed by 100 mg every 8 weeks) if rescue criteria were met at week 16.
The co-primary endpoints were clinical remission and endoscopic response at week 12.
Ailsa Hart, MD, director, IBD Research, and consultant gastroenterologist, St. Mark’s Hospital and Imperial College, both in London, reported the 12-week and 48-week results, which were initially presented at the American College of Gastroenterology (ACG) meeting in October 2024.
At week 12, 56.1% of patients who received guselkumab achieved clinical remission, compared with 21.4% of patients who received placebo. Endoscopic response was achieved in 41.3% of patients treated with guselkumab compared with 21.4% in the placebo group.
Regarding the 48-week results, Hart noted that the rate of clinical remission was more than three times higher with both maintenance doses of guselkumab at 66.1% (200 mg) and 60.0% (100 mg) vs 17.1% with placebo.
Endoscopic response at 48 weeks was achieved in 51.3% of patients on the 200-mg maintenance dose and in 44.3% on the 100-mg maintenance dose, compared with 6.8% of patients on placebo.
In addition, endoscopic remission was achieved in 38.3% of patients in the 200-mg guselkumab group and in 30.4% in the 100-mg guselkumab group, compared with 6.0% in the placebo group.
Safety findings were consistent with the known safety profile of guselkumab in approved indications and other studies in IBD.
“These results complement the GALAXI data and demonstrate that both IV and subcutaneous guselkumab induction are efficacious and therapeutic in Crohn’s disease,” Hart said. Furthermore, data from the ASTRO study demonstrated similar data in the UC population.
As clinicians, this gives us flexibility in how we treat our patients; although, the rationale for choosing subcutaneous or IV is likely to be pragmatic, Hart said.
Additionally, the flexibility of the maintenance therapy, that is, 200 mg subcutaneous guselkumab every 4 weeks or 100 mg every 8 weeks, “is expected to positively affect several parameters of therapy, including increased compliance, hospital avoidance, and better safety profiling,” comoderator Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, said in an interview.
It appears that multiple options will be offered to patients regarding treatment with guselkumab for patients with Crohn’s disease, Bamias said. “Interestingly, a similar multiplicity of options has also been shown for ulcerative colitis, through the QUASAR and ASTRO studies.”
Peyrin-Biroulet declared receiving grants and other/support travel from multiple companies. Hart declared receiving grants and personal fees from multiple companies. Bamias declared receiving grants and personal fees/honoraria as an advisor/lecturer from multiple companies.
A version of this article appeared on Medscape.com.
FROM ECCO 2025