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Weekend Workout, Regular Exercise Are Equals at Lowering GI Disease Risk

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SAN DIEGO — The session started with a question that many in the audience at Digestive Disease Week (DDW) 2025 seemed to relate to: “How many of you find yourself squeezing workouts into a weekend after a hectic work week?”

Although regular exercise three or more times a week is often viewed as preferable, Shiyi Yu, MD, a resident physician in the Department of Gastroenterology at Guangdong Provincial People’s Hospital in Guangzhou, China, had good news for weekend warriors.

Dr. Shiyi Yu



Both patterns reduce digestive disease almost equally.

Her study compared weekend warriors with those she called “active regulars” and sedentary folks to see how activity patterns affect digestive disease risks.

Her bottom line: “Your gut does not care about your schedule.”

The researchers analyzed wrist-based accelerometer data from 89,595 participants in the UK Biobank. To categorize participants as active or inactive, they used the World Health Organization 2020 guidelines for physical activity, which recommend at least 150-300 minutes of moderate-intensity aerobic physical activity or at least 75-150 minutes of vigorous-intensity aerobic physical activity, or an equivalent combination throughout the week. Median age of participants was 63.3 years and 48.8% were men.

They divided participants into three groups:

  • About 43% were weekend warriors who met or exceeded 150 minutes of moderate to vigorous physical activity (MVPA), with 50% or more of total MVPA achieved in 1-2 days.
  • About 23% were active regulars who met or exceeded 150 minutes a week but spread over more days.
  • About 34% were inactive participants who were active less than 150 minutes a week.

The researchers followed the participants for a median of 7.9 years, looking for the incidence of multiple digestive diseases, identified using the International Classification of Diseases, 10th Revision, codes. These included diverticulosis, constipation, metabolic dysfunction–associated steatotic liver disease, cholelithiasis, and gastroesophageal reflux disease. 

Both activity patterns “showed similar risk reduction with no significant difference,” Yu said. At the threshold ≥ 150 minutes, for instance, hazard ratios for any digestive disease were 0.83 for weekend warriors and 0.79 for active regulars, compared with sedentary participants.

The analysis was repeated using a median threshold ≥ 230.4 minutes of MVPA a week, and the researchers found the same results.

As a validation cohort, the researchers used more than 6,000 participants from the National Institutes of Health’s All of Us Research Program with over 6 months of wrist-based accelerometer data.

A recent meta-epidemiology study found that the weekend warrior pattern offers other health benefits, including reducing the risk for cardiovascular disease mortality, mental disorders, and metabolic syndrome.

 

A Pleasant Surprise

The digestive disease study’s findings were “a surprise and a pleasant one,” said Aasma Shaukat, MD, MPH, AGAF, professor of medicine and a gastroenterologist at NYU Grossman School of Medicine, New York City.

Dr. Aasma Shaukat

“We often think if we’re not able to exercise regularly, then there’s no hope for us,” said Shaukat, who moderated the session. “But this implies that even if we have time only during the weekend to engage in physical activity, it still confers benefits in reducing our risk of any GI health disorder, as well as cardiovascular or other health disorders, compared to people inactive at baseline.”

“It gives us flexibility in terms of how we structure our exercise. Obviously, people should try to get into the habit of doing regular activity; it’s more sustainable. But a good alternative, according to this research, is that packing all of that in over the weekend seems to confer benefit. So all is not lost.”

Will this change her conversation with patients moving forward? Absolutely, Shaukat said. She generally recommends physical activity for at least 30 minutes three times a week. Now Shaukat said she can tell patients: “If that’s not possible, take that time out during the weekend for your health”.

This study was funded by grants from the National Natural Science Foundation of China and its Regional Innovation and Development Joint Foundation. Yu and Shaukat reported no disclosures.

A version of this article appeared on Medscape.com.

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SAN DIEGO — The session started with a question that many in the audience at Digestive Disease Week (DDW) 2025 seemed to relate to: “How many of you find yourself squeezing workouts into a weekend after a hectic work week?”

Although regular exercise three or more times a week is often viewed as preferable, Shiyi Yu, MD, a resident physician in the Department of Gastroenterology at Guangdong Provincial People’s Hospital in Guangzhou, China, had good news for weekend warriors.

Dr. Shiyi Yu



Both patterns reduce digestive disease almost equally.

Her study compared weekend warriors with those she called “active regulars” and sedentary folks to see how activity patterns affect digestive disease risks.

Her bottom line: “Your gut does not care about your schedule.”

The researchers analyzed wrist-based accelerometer data from 89,595 participants in the UK Biobank. To categorize participants as active or inactive, they used the World Health Organization 2020 guidelines for physical activity, which recommend at least 150-300 minutes of moderate-intensity aerobic physical activity or at least 75-150 minutes of vigorous-intensity aerobic physical activity, or an equivalent combination throughout the week. Median age of participants was 63.3 years and 48.8% were men.

They divided participants into three groups:

  • About 43% were weekend warriors who met or exceeded 150 minutes of moderate to vigorous physical activity (MVPA), with 50% or more of total MVPA achieved in 1-2 days.
  • About 23% were active regulars who met or exceeded 150 minutes a week but spread over more days.
  • About 34% were inactive participants who were active less than 150 minutes a week.

The researchers followed the participants for a median of 7.9 years, looking for the incidence of multiple digestive diseases, identified using the International Classification of Diseases, 10th Revision, codes. These included diverticulosis, constipation, metabolic dysfunction–associated steatotic liver disease, cholelithiasis, and gastroesophageal reflux disease. 

Both activity patterns “showed similar risk reduction with no significant difference,” Yu said. At the threshold ≥ 150 minutes, for instance, hazard ratios for any digestive disease were 0.83 for weekend warriors and 0.79 for active regulars, compared with sedentary participants.

The analysis was repeated using a median threshold ≥ 230.4 minutes of MVPA a week, and the researchers found the same results.

As a validation cohort, the researchers used more than 6,000 participants from the National Institutes of Health’s All of Us Research Program with over 6 months of wrist-based accelerometer data.

A recent meta-epidemiology study found that the weekend warrior pattern offers other health benefits, including reducing the risk for cardiovascular disease mortality, mental disorders, and metabolic syndrome.

 

A Pleasant Surprise

The digestive disease study’s findings were “a surprise and a pleasant one,” said Aasma Shaukat, MD, MPH, AGAF, professor of medicine and a gastroenterologist at NYU Grossman School of Medicine, New York City.

Dr. Aasma Shaukat

“We often think if we’re not able to exercise regularly, then there’s no hope for us,” said Shaukat, who moderated the session. “But this implies that even if we have time only during the weekend to engage in physical activity, it still confers benefits in reducing our risk of any GI health disorder, as well as cardiovascular or other health disorders, compared to people inactive at baseline.”

“It gives us flexibility in terms of how we structure our exercise. Obviously, people should try to get into the habit of doing regular activity; it’s more sustainable. But a good alternative, according to this research, is that packing all of that in over the weekend seems to confer benefit. So all is not lost.”

Will this change her conversation with patients moving forward? Absolutely, Shaukat said. She generally recommends physical activity for at least 30 minutes three times a week. Now Shaukat said she can tell patients: “If that’s not possible, take that time out during the weekend for your health”.

This study was funded by grants from the National Natural Science Foundation of China and its Regional Innovation and Development Joint Foundation. Yu and Shaukat reported no disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — The session started with a question that many in the audience at Digestive Disease Week (DDW) 2025 seemed to relate to: “How many of you find yourself squeezing workouts into a weekend after a hectic work week?”

Although regular exercise three or more times a week is often viewed as preferable, Shiyi Yu, MD, a resident physician in the Department of Gastroenterology at Guangdong Provincial People’s Hospital in Guangzhou, China, had good news for weekend warriors.

Dr. Shiyi Yu



Both patterns reduce digestive disease almost equally.

Her study compared weekend warriors with those she called “active regulars” and sedentary folks to see how activity patterns affect digestive disease risks.

Her bottom line: “Your gut does not care about your schedule.”

The researchers analyzed wrist-based accelerometer data from 89,595 participants in the UK Biobank. To categorize participants as active or inactive, they used the World Health Organization 2020 guidelines for physical activity, which recommend at least 150-300 minutes of moderate-intensity aerobic physical activity or at least 75-150 minutes of vigorous-intensity aerobic physical activity, or an equivalent combination throughout the week. Median age of participants was 63.3 years and 48.8% were men.

They divided participants into three groups:

  • About 43% were weekend warriors who met or exceeded 150 minutes of moderate to vigorous physical activity (MVPA), with 50% or more of total MVPA achieved in 1-2 days.
  • About 23% were active regulars who met or exceeded 150 minutes a week but spread over more days.
  • About 34% were inactive participants who were active less than 150 minutes a week.

The researchers followed the participants for a median of 7.9 years, looking for the incidence of multiple digestive diseases, identified using the International Classification of Diseases, 10th Revision, codes. These included diverticulosis, constipation, metabolic dysfunction–associated steatotic liver disease, cholelithiasis, and gastroesophageal reflux disease. 

Both activity patterns “showed similar risk reduction with no significant difference,” Yu said. At the threshold ≥ 150 minutes, for instance, hazard ratios for any digestive disease were 0.83 for weekend warriors and 0.79 for active regulars, compared with sedentary participants.

The analysis was repeated using a median threshold ≥ 230.4 minutes of MVPA a week, and the researchers found the same results.

As a validation cohort, the researchers used more than 6,000 participants from the National Institutes of Health’s All of Us Research Program with over 6 months of wrist-based accelerometer data.

A recent meta-epidemiology study found that the weekend warrior pattern offers other health benefits, including reducing the risk for cardiovascular disease mortality, mental disorders, and metabolic syndrome.

 

A Pleasant Surprise

The digestive disease study’s findings were “a surprise and a pleasant one,” said Aasma Shaukat, MD, MPH, AGAF, professor of medicine and a gastroenterologist at NYU Grossman School of Medicine, New York City.

Dr. Aasma Shaukat

“We often think if we’re not able to exercise regularly, then there’s no hope for us,” said Shaukat, who moderated the session. “But this implies that even if we have time only during the weekend to engage in physical activity, it still confers benefits in reducing our risk of any GI health disorder, as well as cardiovascular or other health disorders, compared to people inactive at baseline.”

“It gives us flexibility in terms of how we structure our exercise. Obviously, people should try to get into the habit of doing regular activity; it’s more sustainable. But a good alternative, according to this research, is that packing all of that in over the weekend seems to confer benefit. So all is not lost.”

Will this change her conversation with patients moving forward? Absolutely, Shaukat said. She generally recommends physical activity for at least 30 minutes three times a week. Now Shaukat said she can tell patients: “If that’s not possible, take that time out during the weekend for your health”.

This study was funded by grants from the National Natural Science Foundation of China and its Regional Innovation and Development Joint Foundation. Yu and Shaukat reported no disclosures.

A version of this article appeared on Medscape.com.

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AI-Enhanced Digital Collaborative Care Improves IBS Symptoms

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SAN DIEGO — An artificial intelligence (AI)–enhanced digital collaborative care model led to rapid, clinically significant, and sustained symptom relief for patients with irritable bowel syndrome (IBS) seen at Cleveland Clinic, Cleveland, Ohio, an observational study found.

Stephen Lupe, PsyD

Symptom tracking at 4-week intervals showed that “almost everybody got better” regardless of IBS subtype, with relief starting in the first 4 weeks, Stephen Lupe, PsyD, gastrointestinal psychologist and director of Behavioral Medicine, Department of Gastroenterology, Hepatology, and Nutrition at Cleveland Clinic, Cleveland, said in an interview with GI & Hepatology News.

The findings were presented at Digestive Disease Week (DDW) 2025.

 

Digital Boost to Collaborative Care Model

The combination of dietary interventions and brain-gut behavioral therapy has demonstrated excellent outcomes for patients with IBS, but patients struggle to access these needed services, Lupe noted. A medical home collaborative care model in which patients get care from a multidisciplinary team has been shown to be a good way to successfully deliver this combination of care.

“When you do collaborative in-person care, people get better quicker,” Lupe said.

However, scaling access to this model remains a challenge. For their study, Cleveland Clinic researchers added an AI-enhanced digital platform, Ayble Health, to the in-person collaborative care model to expand access to disease-management services and evaluated whether it improved clinical outcomes for study’s 171 participants, who were recruited via social media advertisements.

Here’s how the platform works. Once a patient enrolls in Ayble Health, a personalized care plan is recommended based on a virtual visit, screening questionnaire, and baseline survey.

The platform includes brain-gut programs, including guided audio content on mindfulness, hypnosis, meditation, cognitive behavioral therapy, and breathing techniques; personalized nutrition support to find and remove trigger foods, a food barcode scanner, and a comprehensive groceries database; and AI-powered wellness tools to help manage and track symptoms. Lupe worked with Ayble Health to develop the platform’s behavioral health content and care pathways.

Patients may choose to follow any combination of three care pathways: A care team overseen by gastro-psychologists, dietitians, and gastroenterologists; a holistic nutrition program including a personalized elimination diet; and a brain-gut behavioral therapy program with gut-directed hypnosis, cognitive behavioral therapy, and acceptance and commitment therapy. They go at their own pace, can connect with Ayble Health’s virtual care team to help with education and goal setting, and continue to consult their Cleveland Clinic providers as needed for evaluation and treatment.

“The care team is still there. We’ve just augmented it to make sure that as many people as possible get behavioral skills training and dietary support, with monitoring between visits — instead of the traditional, ‘I’ll see you in 6 months approach,” Lupe explained.

 

IBS Symptom Scores Improve

Of the study’s 171 patients, 20 had IBS-diarrhea, 23 had IBS-constipation, 32 had IBS-mixed, and 8 had IBS-unspecified. The remaining 88 patients reported IBS without indication of subtype.

At intake, all patients had active IBS symptoms, with scores ≥ 75 on the IBS symptom severity scale (IBS-SSS). Most patients enrolled in more than one care pathway, and 95% of participants completed at least 4 weeks on their chosen pathways.

Overall, patients saw an average 140-point decrease in IBS-SSS from intake through follow-up lasting up to 42 weeks. A drop in IBS-SSS score ≥ 50 points was considered a clinically meaningful change.

Symptom improvements occurred as early as week 4, were sustained and were uniform across IBS subtypes, suggesting that the AI-enhanced digital collaborative care model has wide utility in patients with IBS, Lupe said.

Patients with the most severe IBS symptoms showed the greatest improvement, but even 50% of those with mild symptoms had clinically meaningful changes in IBS-SSS.

Improvement in IBS symptoms was seen across all care pathways, but the combination of multiple pathways improved outcomes better than a single care pathway alone. The combination of nutrition and brain-gut behavioral therapy demonstrated the greatest reduction in IBS-SSS scores and proportion of patients achieving clinically meaningful results (95%).

The digital comprehensive car model for IBS is now “up and running” at Cleveland Clinic, and the team plans to proactively reach out to patients with gastrointestinal disorders recently seen at their center to alert them to the availability of this tool, Lupe said.

A randomized controlled trial is planned to further validate these observational findings, he added.

 

‘Wave of the Future’

The digital collaborative care model is “innovative, and I think is the wave of the future,” Kyle Staller, MD, MPH, gastroenterologist and director of the Gastrointestinal Motility Laboratory at Massachusetts General Hospital, Boston, who wasn’t involved in the study, told GI & Hepatology News.

Dr. Kyle Staller

“These digital platforms bundle nondrug options, such as cognitive-behavioral therapy, dietary therapy, hypnotherapy, so patients can choose what suits them, rather than the gastroenterologist hunting down each individual resource, which requires a lot of work,” Staller said.

The study “provides real-world evidence that a deliberative, digital, collaborative care model that houses various types of nondrug IBS treatment under one roof can provide meaningful benefit to patients,” Staller told GI & Hepatology News.

Importantly, he said, “patients chose which option they wanted. At the end of the day, the way that we should be thinking about IBS care is really making sure that we engage the patient with treatment choices,” Staller said.

This study had no specific funding. Three authors had relationships with Ayble Health. Lupe is a scientific advisor for Boomerang Health and paid lecturer for Takeda Pharmaceuticals. Staller disclosed having relationships with Mahana Therapeutics, Ardelyx Inc, Gemelli Biotech, Salix Pharmaceuticals, and Takeda Pharmaceuticals.

A version of this article appeared on Medscape.com.

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SAN DIEGO — An artificial intelligence (AI)–enhanced digital collaborative care model led to rapid, clinically significant, and sustained symptom relief for patients with irritable bowel syndrome (IBS) seen at Cleveland Clinic, Cleveland, Ohio, an observational study found.

Stephen Lupe, PsyD

Symptom tracking at 4-week intervals showed that “almost everybody got better” regardless of IBS subtype, with relief starting in the first 4 weeks, Stephen Lupe, PsyD, gastrointestinal psychologist and director of Behavioral Medicine, Department of Gastroenterology, Hepatology, and Nutrition at Cleveland Clinic, Cleveland, said in an interview with GI & Hepatology News.

The findings were presented at Digestive Disease Week (DDW) 2025.

 

Digital Boost to Collaborative Care Model

The combination of dietary interventions and brain-gut behavioral therapy has demonstrated excellent outcomes for patients with IBS, but patients struggle to access these needed services, Lupe noted. A medical home collaborative care model in which patients get care from a multidisciplinary team has been shown to be a good way to successfully deliver this combination of care.

“When you do collaborative in-person care, people get better quicker,” Lupe said.

However, scaling access to this model remains a challenge. For their study, Cleveland Clinic researchers added an AI-enhanced digital platform, Ayble Health, to the in-person collaborative care model to expand access to disease-management services and evaluated whether it improved clinical outcomes for study’s 171 participants, who were recruited via social media advertisements.

Here’s how the platform works. Once a patient enrolls in Ayble Health, a personalized care plan is recommended based on a virtual visit, screening questionnaire, and baseline survey.

The platform includes brain-gut programs, including guided audio content on mindfulness, hypnosis, meditation, cognitive behavioral therapy, and breathing techniques; personalized nutrition support to find and remove trigger foods, a food barcode scanner, and a comprehensive groceries database; and AI-powered wellness tools to help manage and track symptoms. Lupe worked with Ayble Health to develop the platform’s behavioral health content and care pathways.

Patients may choose to follow any combination of three care pathways: A care team overseen by gastro-psychologists, dietitians, and gastroenterologists; a holistic nutrition program including a personalized elimination diet; and a brain-gut behavioral therapy program with gut-directed hypnosis, cognitive behavioral therapy, and acceptance and commitment therapy. They go at their own pace, can connect with Ayble Health’s virtual care team to help with education and goal setting, and continue to consult their Cleveland Clinic providers as needed for evaluation and treatment.

“The care team is still there. We’ve just augmented it to make sure that as many people as possible get behavioral skills training and dietary support, with monitoring between visits — instead of the traditional, ‘I’ll see you in 6 months approach,” Lupe explained.

 

IBS Symptom Scores Improve

Of the study’s 171 patients, 20 had IBS-diarrhea, 23 had IBS-constipation, 32 had IBS-mixed, and 8 had IBS-unspecified. The remaining 88 patients reported IBS without indication of subtype.

At intake, all patients had active IBS symptoms, with scores ≥ 75 on the IBS symptom severity scale (IBS-SSS). Most patients enrolled in more than one care pathway, and 95% of participants completed at least 4 weeks on their chosen pathways.

Overall, patients saw an average 140-point decrease in IBS-SSS from intake through follow-up lasting up to 42 weeks. A drop in IBS-SSS score ≥ 50 points was considered a clinically meaningful change.

Symptom improvements occurred as early as week 4, were sustained and were uniform across IBS subtypes, suggesting that the AI-enhanced digital collaborative care model has wide utility in patients with IBS, Lupe said.

Patients with the most severe IBS symptoms showed the greatest improvement, but even 50% of those with mild symptoms had clinically meaningful changes in IBS-SSS.

Improvement in IBS symptoms was seen across all care pathways, but the combination of multiple pathways improved outcomes better than a single care pathway alone. The combination of nutrition and brain-gut behavioral therapy demonstrated the greatest reduction in IBS-SSS scores and proportion of patients achieving clinically meaningful results (95%).

The digital comprehensive car model for IBS is now “up and running” at Cleveland Clinic, and the team plans to proactively reach out to patients with gastrointestinal disorders recently seen at their center to alert them to the availability of this tool, Lupe said.

A randomized controlled trial is planned to further validate these observational findings, he added.

 

‘Wave of the Future’

The digital collaborative care model is “innovative, and I think is the wave of the future,” Kyle Staller, MD, MPH, gastroenterologist and director of the Gastrointestinal Motility Laboratory at Massachusetts General Hospital, Boston, who wasn’t involved in the study, told GI & Hepatology News.

Dr. Kyle Staller

“These digital platforms bundle nondrug options, such as cognitive-behavioral therapy, dietary therapy, hypnotherapy, so patients can choose what suits them, rather than the gastroenterologist hunting down each individual resource, which requires a lot of work,” Staller said.

The study “provides real-world evidence that a deliberative, digital, collaborative care model that houses various types of nondrug IBS treatment under one roof can provide meaningful benefit to patients,” Staller told GI & Hepatology News.

Importantly, he said, “patients chose which option they wanted. At the end of the day, the way that we should be thinking about IBS care is really making sure that we engage the patient with treatment choices,” Staller said.

This study had no specific funding. Three authors had relationships with Ayble Health. Lupe is a scientific advisor for Boomerang Health and paid lecturer for Takeda Pharmaceuticals. Staller disclosed having relationships with Mahana Therapeutics, Ardelyx Inc, Gemelli Biotech, Salix Pharmaceuticals, and Takeda Pharmaceuticals.

A version of this article appeared on Medscape.com.

SAN DIEGO — An artificial intelligence (AI)–enhanced digital collaborative care model led to rapid, clinically significant, and sustained symptom relief for patients with irritable bowel syndrome (IBS) seen at Cleveland Clinic, Cleveland, Ohio, an observational study found.

Stephen Lupe, PsyD

Symptom tracking at 4-week intervals showed that “almost everybody got better” regardless of IBS subtype, with relief starting in the first 4 weeks, Stephen Lupe, PsyD, gastrointestinal psychologist and director of Behavioral Medicine, Department of Gastroenterology, Hepatology, and Nutrition at Cleveland Clinic, Cleveland, said in an interview with GI & Hepatology News.

The findings were presented at Digestive Disease Week (DDW) 2025.

 

Digital Boost to Collaborative Care Model

The combination of dietary interventions and brain-gut behavioral therapy has demonstrated excellent outcomes for patients with IBS, but patients struggle to access these needed services, Lupe noted. A medical home collaborative care model in which patients get care from a multidisciplinary team has been shown to be a good way to successfully deliver this combination of care.

“When you do collaborative in-person care, people get better quicker,” Lupe said.

However, scaling access to this model remains a challenge. For their study, Cleveland Clinic researchers added an AI-enhanced digital platform, Ayble Health, to the in-person collaborative care model to expand access to disease-management services and evaluated whether it improved clinical outcomes for study’s 171 participants, who were recruited via social media advertisements.

Here’s how the platform works. Once a patient enrolls in Ayble Health, a personalized care plan is recommended based on a virtual visit, screening questionnaire, and baseline survey.

The platform includes brain-gut programs, including guided audio content on mindfulness, hypnosis, meditation, cognitive behavioral therapy, and breathing techniques; personalized nutrition support to find and remove trigger foods, a food barcode scanner, and a comprehensive groceries database; and AI-powered wellness tools to help manage and track symptoms. Lupe worked with Ayble Health to develop the platform’s behavioral health content and care pathways.

Patients may choose to follow any combination of three care pathways: A care team overseen by gastro-psychologists, dietitians, and gastroenterologists; a holistic nutrition program including a personalized elimination diet; and a brain-gut behavioral therapy program with gut-directed hypnosis, cognitive behavioral therapy, and acceptance and commitment therapy. They go at their own pace, can connect with Ayble Health’s virtual care team to help with education and goal setting, and continue to consult their Cleveland Clinic providers as needed for evaluation and treatment.

“The care team is still there. We’ve just augmented it to make sure that as many people as possible get behavioral skills training and dietary support, with monitoring between visits — instead of the traditional, ‘I’ll see you in 6 months approach,” Lupe explained.

 

IBS Symptom Scores Improve

Of the study’s 171 patients, 20 had IBS-diarrhea, 23 had IBS-constipation, 32 had IBS-mixed, and 8 had IBS-unspecified. The remaining 88 patients reported IBS without indication of subtype.

At intake, all patients had active IBS symptoms, with scores ≥ 75 on the IBS symptom severity scale (IBS-SSS). Most patients enrolled in more than one care pathway, and 95% of participants completed at least 4 weeks on their chosen pathways.

Overall, patients saw an average 140-point decrease in IBS-SSS from intake through follow-up lasting up to 42 weeks. A drop in IBS-SSS score ≥ 50 points was considered a clinically meaningful change.

Symptom improvements occurred as early as week 4, were sustained and were uniform across IBS subtypes, suggesting that the AI-enhanced digital collaborative care model has wide utility in patients with IBS, Lupe said.

Patients with the most severe IBS symptoms showed the greatest improvement, but even 50% of those with mild symptoms had clinically meaningful changes in IBS-SSS.

Improvement in IBS symptoms was seen across all care pathways, but the combination of multiple pathways improved outcomes better than a single care pathway alone. The combination of nutrition and brain-gut behavioral therapy demonstrated the greatest reduction in IBS-SSS scores and proportion of patients achieving clinically meaningful results (95%).

The digital comprehensive car model for IBS is now “up and running” at Cleveland Clinic, and the team plans to proactively reach out to patients with gastrointestinal disorders recently seen at their center to alert them to the availability of this tool, Lupe said.

A randomized controlled trial is planned to further validate these observational findings, he added.

 

‘Wave of the Future’

The digital collaborative care model is “innovative, and I think is the wave of the future,” Kyle Staller, MD, MPH, gastroenterologist and director of the Gastrointestinal Motility Laboratory at Massachusetts General Hospital, Boston, who wasn’t involved in the study, told GI & Hepatology News.

Dr. Kyle Staller

“These digital platforms bundle nondrug options, such as cognitive-behavioral therapy, dietary therapy, hypnotherapy, so patients can choose what suits them, rather than the gastroenterologist hunting down each individual resource, which requires a lot of work,” Staller said.

The study “provides real-world evidence that a deliberative, digital, collaborative care model that houses various types of nondrug IBS treatment under one roof can provide meaningful benefit to patients,” Staller told GI & Hepatology News.

Importantly, he said, “patients chose which option they wanted. At the end of the day, the way that we should be thinking about IBS care is really making sure that we engage the patient with treatment choices,” Staller said.

This study had no specific funding. Three authors had relationships with Ayble Health. Lupe is a scientific advisor for Boomerang Health and paid lecturer for Takeda Pharmaceuticals. Staller disclosed having relationships with Mahana Therapeutics, Ardelyx Inc, Gemelli Biotech, Salix Pharmaceuticals, and Takeda Pharmaceuticals.

A version of this article appeared on Medscape.com.

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IBS: Mental Health Factors and Comorbidities

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IBS: Mental Health Factors and Comorbidities

Click to view more from Gastroenterology Data Trends 2025. 

References
  1. Staudacher HM, Black CJ, Teasdale SB, Mikocka-Walus A, Keefer L. Irritable bowel syndrome and mental health comorbidity - approach to multidisciplinary management. Nat Rev Gastroenterol Hepatol. 2023;20(9):582-596. doi:10.1038/s41575-023-00794-z
  2. Ballou S, Vasant DH, Guadagnoli L, et al. A primer for the gastroenterology provider on psychosocial assessment of patients with disorders of gut-brain interaction. Neurogastroenterol Motil. 2024;36(12):e14894. doi:10.1111/nmo.14894
  3. Keefer L, Ballou SK, Drossman DA, Ringstrom G, Elsenbruch S, Ljótsson B. A Rome Working Team Report on Brain-Gut Behavior Therapies for Disorders of Gut-Brain Interaction. Gastroenterology. 2022;162(1):300-315. doi:10.1053/j.gastro.2021.09.015
  4. Goodoory VC, Khasawneh M, Thakur ER, et al. Effect of Brain-Gut Behavioral Treatments on Abdominal Pain in Irritable Bowel Syndrome: Systematic Review and Network Meta-Analysis. Gastroenterology. 2024;167(5):934-943.e5. doi:10.1053/j.gastro.2024.05.010
  5. Chang L, Sultan S, Lembo A, Verne GN, Smalley W, Heidelbaugh JJ. AGA Clinical Practice Guideline on the Pharmacological Management of Irritable Bowel Syndrome With Constipation. Gastroenterology. 2022;163(1):118-136. doi:10.1053/j.gastro.2022.04.016
  6. Drossman DA, Tack J, Ford AC, Szigethy E, Törnblom H, Van Oudenhove L. Neuromodulators for Functional Gastrointestinal Disorders (Disorders of Gut-Brain Interaction): A Rome Foundation Working Team Report. Gastroenterology. 2018;154(4):1140-1171.e1. doi:10.1053/j.gastro.2017.11.279
  7. Hasan SS, Ballou S, Keefer L, Vasant DH. Improving access to gut-directed hypnotherapy for irritable bowel syndrome in the digital therapeutics’ era: Are mobile applications a “smart” solution? Neurogastroenterol Motil. 2023;35(4):e14554. doi:10.1111/nmo.14554
  8. Tarar ZI, Farooq U, Zafar Y, et al. Burden of anxiety and depression among hospitalized patients with irritable bowel syndrome: a nationwide analysis. Ir J Med Sci. 2023;192(5):2159-2166. doi:10.1007/s11845-022-03258-6
  9. Barbara G, Aziz I, Ballou S, et al. Rome Foundation Working Team Report on overlap in disorders of gut-brain interaction. Nat Rev Gastroenterol Hepatol. doi:10.1038/s41575-024-01033-9
  10. Thakur ER, Kunik M, Jarbrink-Sehgal ME, Lackner J, Dindo L, El-Serag H. Behavior Medicine Management of Irritable Bowel Syndrome: A Referral Toolkit for Gastroenterology Providers. 2018. Accessed February 19, 2025. https://www.mirecc.va.gov/VISN16/docs/ibs-referral-toolkit.pdf
  11. Irritable bowel syndrome (IBS). Johns Hopkins Medicine website. Accessed February 19, 2025. https://www.hopkinsmedicine.org/health/conditionsanddiseases/irritable-bowel-syndrome-ibs
  12. Burton-Murray H, Guadagnoli L, Kamp K, et al. Rome Foundation Working Team Report: Consensus Statement on the Design and Conduct of Behavioural Clinical Trials for Disorders of Gut-Brain Interaction. Aliment Pharmacol Ther. 2025;61(5):787-802. doi:10.1111/apt.18482
  13. Rome GastroPsych. Rome Foundation website. Accessed February 19, 2025. https://romegipsych.org/
  14. Scarlata K, Riehl M. Mind Your Gut: The Science-based, Whole-body Guide to Living Well with IBS. Hachette Book Group, 2025.
  15. IFFGD International Foundation for Gastrointestinal Disorders. IFFGD website. January 10, 2025. Accessed February 19, 2025. https://iffgd.org/
  16. GI Psychology: Mind Your Gut website. April 2, 2024. Accessed February 19, 2025. https://www.gipsychology.com/
  17. Drossman DA, Ruddy J. Gut Feelings: Disorders of the Gut-Brain Interaction (DGBI) and the Patient-Doctor Relationship. DrossmanCare Chapel Hill, 2020.
  18. Tuesday Night IBS website. Accessed February 19, 2025. https://www.tuesdaynightibs.com/
Author and Disclosure Information

Lin Chang, MD
Professor, David Geffen School of Medicine,
UCLA; Vice-Chief, Vatche and Tamar
Manoukian, Division of Digestive Diseases,
UCLA Digestive Diseases Center,
Los Angeles, California

Disclosures: Serve(d) as a director, officer, partner, employee, advisor,
consultant, or trustee for: Ardelyx; Alfasigma; Atmo; GLaxoSmithKline;
Food Marble; Vibrant; Nerva; Received research grant from: AnX Robotica;
Ironwood; Received income in an amount equal to or greater than $250
from: Alfasigma; Atmo; GLaxoSmithKline; Food Marble; Have stock options
in: Trellus Health; Food Marble; ModifyHealth

Laurie A. Keefer, PhD
Professor, Department of Medicine and
Psychiatry, Division of Gastroenterology, Icahn
School of Medicine at Mount Sinai; Gastro
Psychologist, Inflammatory Bowel Disease Center,
Mount Sinai Hospital, New York, New York

Disclosures: Serve(d) as a director, officer, partner, employee, advisor,
consultant, or trustee for: AbbVie; Pfizer; Eli Lilly; Reckitt Health; Johnson
and Johnson; Rome Foundation; Received research grant from: Ardelyx
Have a 5% or greater equity interest in: Trellus Health

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Lin Chang, MD
Professor, David Geffen School of Medicine,
UCLA; Vice-Chief, Vatche and Tamar
Manoukian, Division of Digestive Diseases,
UCLA Digestive Diseases Center,
Los Angeles, California

Disclosures: Serve(d) as a director, officer, partner, employee, advisor,
consultant, or trustee for: Ardelyx; Alfasigma; Atmo; GLaxoSmithKline;
Food Marble; Vibrant; Nerva; Received research grant from: AnX Robotica;
Ironwood; Received income in an amount equal to or greater than $250
from: Alfasigma; Atmo; GLaxoSmithKline; Food Marble; Have stock options
in: Trellus Health; Food Marble; ModifyHealth

Laurie A. Keefer, PhD
Professor, Department of Medicine and
Psychiatry, Division of Gastroenterology, Icahn
School of Medicine at Mount Sinai; Gastro
Psychologist, Inflammatory Bowel Disease Center,
Mount Sinai Hospital, New York, New York

Disclosures: Serve(d) as a director, officer, partner, employee, advisor,
consultant, or trustee for: AbbVie; Pfizer; Eli Lilly; Reckitt Health; Johnson
and Johnson; Rome Foundation; Received research grant from: Ardelyx
Have a 5% or greater equity interest in: Trellus Health

Author and Disclosure Information

Lin Chang, MD
Professor, David Geffen School of Medicine,
UCLA; Vice-Chief, Vatche and Tamar
Manoukian, Division of Digestive Diseases,
UCLA Digestive Diseases Center,
Los Angeles, California

Disclosures: Serve(d) as a director, officer, partner, employee, advisor,
consultant, or trustee for: Ardelyx; Alfasigma; Atmo; GLaxoSmithKline;
Food Marble; Vibrant; Nerva; Received research grant from: AnX Robotica;
Ironwood; Received income in an amount equal to or greater than $250
from: Alfasigma; Atmo; GLaxoSmithKline; Food Marble; Have stock options
in: Trellus Health; Food Marble; ModifyHealth

Laurie A. Keefer, PhD
Professor, Department of Medicine and
Psychiatry, Division of Gastroenterology, Icahn
School of Medicine at Mount Sinai; Gastro
Psychologist, Inflammatory Bowel Disease Center,
Mount Sinai Hospital, New York, New York

Disclosures: Serve(d) as a director, officer, partner, employee, advisor,
consultant, or trustee for: AbbVie; Pfizer; Eli Lilly; Reckitt Health; Johnson
and Johnson; Rome Foundation; Received research grant from: Ardelyx
Have a 5% or greater equity interest in: Trellus Health

Click to view more from Gastroenterology Data Trends 2025. 

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References
  1. Staudacher HM, Black CJ, Teasdale SB, Mikocka-Walus A, Keefer L. Irritable bowel syndrome and mental health comorbidity - approach to multidisciplinary management. Nat Rev Gastroenterol Hepatol. 2023;20(9):582-596. doi:10.1038/s41575-023-00794-z
  2. Ballou S, Vasant DH, Guadagnoli L, et al. A primer for the gastroenterology provider on psychosocial assessment of patients with disorders of gut-brain interaction. Neurogastroenterol Motil. 2024;36(12):e14894. doi:10.1111/nmo.14894
  3. Keefer L, Ballou SK, Drossman DA, Ringstrom G, Elsenbruch S, Ljótsson B. A Rome Working Team Report on Brain-Gut Behavior Therapies for Disorders of Gut-Brain Interaction. Gastroenterology. 2022;162(1):300-315. doi:10.1053/j.gastro.2021.09.015
  4. Goodoory VC, Khasawneh M, Thakur ER, et al. Effect of Brain-Gut Behavioral Treatments on Abdominal Pain in Irritable Bowel Syndrome: Systematic Review and Network Meta-Analysis. Gastroenterology. 2024;167(5):934-943.e5. doi:10.1053/j.gastro.2024.05.010
  5. Chang L, Sultan S, Lembo A, Verne GN, Smalley W, Heidelbaugh JJ. AGA Clinical Practice Guideline on the Pharmacological Management of Irritable Bowel Syndrome With Constipation. Gastroenterology. 2022;163(1):118-136. doi:10.1053/j.gastro.2022.04.016
  6. Drossman DA, Tack J, Ford AC, Szigethy E, Törnblom H, Van Oudenhove L. Neuromodulators for Functional Gastrointestinal Disorders (Disorders of Gut-Brain Interaction): A Rome Foundation Working Team Report. Gastroenterology. 2018;154(4):1140-1171.e1. doi:10.1053/j.gastro.2017.11.279
  7. Hasan SS, Ballou S, Keefer L, Vasant DH. Improving access to gut-directed hypnotherapy for irritable bowel syndrome in the digital therapeutics’ era: Are mobile applications a “smart” solution? Neurogastroenterol Motil. 2023;35(4):e14554. doi:10.1111/nmo.14554
  8. Tarar ZI, Farooq U, Zafar Y, et al. Burden of anxiety and depression among hospitalized patients with irritable bowel syndrome: a nationwide analysis. Ir J Med Sci. 2023;192(5):2159-2166. doi:10.1007/s11845-022-03258-6
  9. Barbara G, Aziz I, Ballou S, et al. Rome Foundation Working Team Report on overlap in disorders of gut-brain interaction. Nat Rev Gastroenterol Hepatol. doi:10.1038/s41575-024-01033-9
  10. Thakur ER, Kunik M, Jarbrink-Sehgal ME, Lackner J, Dindo L, El-Serag H. Behavior Medicine Management of Irritable Bowel Syndrome: A Referral Toolkit for Gastroenterology Providers. 2018. Accessed February 19, 2025. https://www.mirecc.va.gov/VISN16/docs/ibs-referral-toolkit.pdf
  11. Irritable bowel syndrome (IBS). Johns Hopkins Medicine website. Accessed February 19, 2025. https://www.hopkinsmedicine.org/health/conditionsanddiseases/irritable-bowel-syndrome-ibs
  12. Burton-Murray H, Guadagnoli L, Kamp K, et al. Rome Foundation Working Team Report: Consensus Statement on the Design and Conduct of Behavioural Clinical Trials for Disorders of Gut-Brain Interaction. Aliment Pharmacol Ther. 2025;61(5):787-802. doi:10.1111/apt.18482
  13. Rome GastroPsych. Rome Foundation website. Accessed February 19, 2025. https://romegipsych.org/
  14. Scarlata K, Riehl M. Mind Your Gut: The Science-based, Whole-body Guide to Living Well with IBS. Hachette Book Group, 2025.
  15. IFFGD International Foundation for Gastrointestinal Disorders. IFFGD website. January 10, 2025. Accessed February 19, 2025. https://iffgd.org/
  16. GI Psychology: Mind Your Gut website. April 2, 2024. Accessed February 19, 2025. https://www.gipsychology.com/
  17. Drossman DA, Ruddy J. Gut Feelings: Disorders of the Gut-Brain Interaction (DGBI) and the Patient-Doctor Relationship. DrossmanCare Chapel Hill, 2020.
  18. Tuesday Night IBS website. Accessed February 19, 2025. https://www.tuesdaynightibs.com/
References
  1. Staudacher HM, Black CJ, Teasdale SB, Mikocka-Walus A, Keefer L. Irritable bowel syndrome and mental health comorbidity - approach to multidisciplinary management. Nat Rev Gastroenterol Hepatol. 2023;20(9):582-596. doi:10.1038/s41575-023-00794-z
  2. Ballou S, Vasant DH, Guadagnoli L, et al. A primer for the gastroenterology provider on psychosocial assessment of patients with disorders of gut-brain interaction. Neurogastroenterol Motil. 2024;36(12):e14894. doi:10.1111/nmo.14894
  3. Keefer L, Ballou SK, Drossman DA, Ringstrom G, Elsenbruch S, Ljótsson B. A Rome Working Team Report on Brain-Gut Behavior Therapies for Disorders of Gut-Brain Interaction. Gastroenterology. 2022;162(1):300-315. doi:10.1053/j.gastro.2021.09.015
  4. Goodoory VC, Khasawneh M, Thakur ER, et al. Effect of Brain-Gut Behavioral Treatments on Abdominal Pain in Irritable Bowel Syndrome: Systematic Review and Network Meta-Analysis. Gastroenterology. 2024;167(5):934-943.e5. doi:10.1053/j.gastro.2024.05.010
  5. Chang L, Sultan S, Lembo A, Verne GN, Smalley W, Heidelbaugh JJ. AGA Clinical Practice Guideline on the Pharmacological Management of Irritable Bowel Syndrome With Constipation. Gastroenterology. 2022;163(1):118-136. doi:10.1053/j.gastro.2022.04.016
  6. Drossman DA, Tack J, Ford AC, Szigethy E, Törnblom H, Van Oudenhove L. Neuromodulators for Functional Gastrointestinal Disorders (Disorders of Gut-Brain Interaction): A Rome Foundation Working Team Report. Gastroenterology. 2018;154(4):1140-1171.e1. doi:10.1053/j.gastro.2017.11.279
  7. Hasan SS, Ballou S, Keefer L, Vasant DH. Improving access to gut-directed hypnotherapy for irritable bowel syndrome in the digital therapeutics’ era: Are mobile applications a “smart” solution? Neurogastroenterol Motil. 2023;35(4):e14554. doi:10.1111/nmo.14554
  8. Tarar ZI, Farooq U, Zafar Y, et al. Burden of anxiety and depression among hospitalized patients with irritable bowel syndrome: a nationwide analysis. Ir J Med Sci. 2023;192(5):2159-2166. doi:10.1007/s11845-022-03258-6
  9. Barbara G, Aziz I, Ballou S, et al. Rome Foundation Working Team Report on overlap in disorders of gut-brain interaction. Nat Rev Gastroenterol Hepatol. doi:10.1038/s41575-024-01033-9
  10. Thakur ER, Kunik M, Jarbrink-Sehgal ME, Lackner J, Dindo L, El-Serag H. Behavior Medicine Management of Irritable Bowel Syndrome: A Referral Toolkit for Gastroenterology Providers. 2018. Accessed February 19, 2025. https://www.mirecc.va.gov/VISN16/docs/ibs-referral-toolkit.pdf
  11. Irritable bowel syndrome (IBS). Johns Hopkins Medicine website. Accessed February 19, 2025. https://www.hopkinsmedicine.org/health/conditionsanddiseases/irritable-bowel-syndrome-ibs
  12. Burton-Murray H, Guadagnoli L, Kamp K, et al. Rome Foundation Working Team Report: Consensus Statement on the Design and Conduct of Behavioural Clinical Trials for Disorders of Gut-Brain Interaction. Aliment Pharmacol Ther. 2025;61(5):787-802. doi:10.1111/apt.18482
  13. Rome GastroPsych. Rome Foundation website. Accessed February 19, 2025. https://romegipsych.org/
  14. Scarlata K, Riehl M. Mind Your Gut: The Science-based, Whole-body Guide to Living Well with IBS. Hachette Book Group, 2025.
  15. IFFGD International Foundation for Gastrointestinal Disorders. IFFGD website. January 10, 2025. Accessed February 19, 2025. https://iffgd.org/
  16. GI Psychology: Mind Your Gut website. April 2, 2024. Accessed February 19, 2025. https://www.gipsychology.com/
  17. Drossman DA, Ruddy J. Gut Feelings: Disorders of the Gut-Brain Interaction (DGBI) and the Patient-Doctor Relationship. DrossmanCare Chapel Hill, 2020.
  18. Tuesday Night IBS website. Accessed February 19, 2025. https://www.tuesdaynightibs.com/
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IBS: Mental Health Factors and Comorbidities

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IBS: Mental Health Factors and Comorbidities

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Irritable bowel syndrome (IBS), a disorder of gut-brain interaction, affects up to 10% of the global population.1 Psychological symptoms often are associated with IBS, increasing its burden and affecting quality of life.1-3 About one third of patients with IBS experience anxiety or depression.1 Multidisciplinary care, involving gastroenterologists, psychologists, and dietitians, is crucial to address both physical and emotional symptoms in patients with IBS.1

Effective clinical pathways vary by patient profile. Some patients may have maladaptive cognitive processes that affect coping with IBS (e.g., avoidance behaviors and symptom-related anxiety) but do not meet criteria for a psychiatric disorder.2 For these patients, referral to brain-gut behavior therapy (BGBT) is advised.2 BGBTs can include cognitive behavioral therapy (CBT), gut-directed hypnotherapy, and mindfulness-based interventions, among others.3 These approaches can improve not only mental health symptoms and symptom-related stress but also gastrointestinal (GI) symptoms.4 For patients with psychiatric illnesses, referrals to psychiatrists or psychologists specialized in the patient’s specific comorbid condition are recommended.2 It is also helpful for GI professionals to familiarize themselves with a few antidepressant medications for symptom-specific anxiety or mood symptoms when a psychiatrist is unavailable.5,6 Some antidepressants, called central neuromodulators, also improve IBS symptoms.5,6

Access to integrated IBS care remains a challenge. The number of GI psychologists is limited. Most digital applications aiming to bridge this gap have limitations, such as nonpersonalized approaches and problems with engagement.7 Other options to provide care for patients with IBS and psychological symptoms include support groups or nurse-led self-management programs, education, patient advocacy organizations, and placement of educational material in clinic waiting areas.3

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New Fecal Product Expected to Enhance Microbiome Research

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The US National Institute of Standards and Technology (NIST) has developed precisely measured human fecal material to foster a new era in gut microbiome research. 

Scott A. Jackson

According to AGA’s Center for Gut Microbiome Research & Education, this critical resource will help advance the utility and reproducibility of microbiome-based diagnostics — “which still remain relatively meaningless clinically, although patients continue to buy direct-to-consumer tests, and a standard reference material will mean there’s a better way to ensure quality control and accuracy.” 

Though not a therapeutic, Human Fecal Material RM is expected to speed up gastrointestinal (GI) therapeutics since many microbiome-based drugs are inspired by fecal transplants with human stool as the developmental starting point. A standardized reference material will be an important resource as industry develops and tests new drugs. It can be purchased online at the NIST Store (shop.nist.gov).

The product consists of eight frozen vials of exhaustively studied human feces suspended in aqueous solution. Available are more than 25 pages of data identifying the key microbes and biomolecules in the material. Scientists, including those working at biopharmaceutical and biotech companies, can use this material to further their research and develop new drugs that target the microbiome, including treatments that contain living bacteria. 

 

Development

According to NIST, the stool material is “the most precisely measured, scientifically analyzed, and richly characterized human fecal standard ever produced. 

“The project ran for about 6 years from start to finish, the last 2 for manufacturing, characterization, and writing,” said NIST molecular geneticist Scott A. Jackson, PhD, who helped develop the product. “We hope our reference material will lay the foundation for gut microbiome research to thrive and reach its full potential.” 

Dr. Sudhir K. Dutta


As founder of NIST’s Complex Microbial Systems Group, Jackson is leading international efforts to improve microbiome and metagenomic measurements by organizing inter-lab studies and refining reference materials and methods. 

The project collected stool from two cohorts of donors, ie, vegetarians and omnivores, with each cohort comprising four to six donors. Material from each cohort was pooled and homogenized before being aliquoted into 5000 vials per cohort. About 300 tubes from each cohort were picked, and aliquots then underwent multiomic analyses. 

Offering his perspective on the new product, Sudhir K. Dutta, MBBS, associate professor in the Division of Gastroenterology and Hepatology at Johns Hopkins University School of Medicine, Baltimore, said, “This tool will be 100% useful for microbiome research.”

And according to Lori Holtz, MD, MSPH, professor of pediatric gastroenterology, hepatology, and nutrition at Washington University School of Medicine in St. Louis, Missouri, the material will aid microbiome research by allowing interpretability and repeatability across studies. “Microbiome research is a relatively new field, and protocols differ from group to group and lab to lab, so it’s been difficult to compare results across studies,” she told GI & Hepatology News. “A standard stool product will allow for greater comparability in preclinical studies and later clinical trials testing interventions to alter the microbiome.”

The NIST developers are looking forward to reaction from the GI research community. “Over the last several years, we’ve released smaller pilot batches of material to smaller groups of stakeholders,” said Jackson. “We’ve used the feedback on these earlier batches to inform the manufacturing and characterization of the final batch that was released in March, but we don’t yet have any feedback yet on the current material.”

Dr. Lori Holtz



Jackson, Dutta, and Holtz disclosed having no relevant competing interests.

A version of this article appeared on Medscape.com.

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The US National Institute of Standards and Technology (NIST) has developed precisely measured human fecal material to foster a new era in gut microbiome research. 

Scott A. Jackson

According to AGA’s Center for Gut Microbiome Research & Education, this critical resource will help advance the utility and reproducibility of microbiome-based diagnostics — “which still remain relatively meaningless clinically, although patients continue to buy direct-to-consumer tests, and a standard reference material will mean there’s a better way to ensure quality control and accuracy.” 

Though not a therapeutic, Human Fecal Material RM is expected to speed up gastrointestinal (GI) therapeutics since many microbiome-based drugs are inspired by fecal transplants with human stool as the developmental starting point. A standardized reference material will be an important resource as industry develops and tests new drugs. It can be purchased online at the NIST Store (shop.nist.gov).

The product consists of eight frozen vials of exhaustively studied human feces suspended in aqueous solution. Available are more than 25 pages of data identifying the key microbes and biomolecules in the material. Scientists, including those working at biopharmaceutical and biotech companies, can use this material to further their research and develop new drugs that target the microbiome, including treatments that contain living bacteria. 

 

Development

According to NIST, the stool material is “the most precisely measured, scientifically analyzed, and richly characterized human fecal standard ever produced. 

“The project ran for about 6 years from start to finish, the last 2 for manufacturing, characterization, and writing,” said NIST molecular geneticist Scott A. Jackson, PhD, who helped develop the product. “We hope our reference material will lay the foundation for gut microbiome research to thrive and reach its full potential.” 

Dr. Sudhir K. Dutta


As founder of NIST’s Complex Microbial Systems Group, Jackson is leading international efforts to improve microbiome and metagenomic measurements by organizing inter-lab studies and refining reference materials and methods. 

The project collected stool from two cohorts of donors, ie, vegetarians and omnivores, with each cohort comprising four to six donors. Material from each cohort was pooled and homogenized before being aliquoted into 5000 vials per cohort. About 300 tubes from each cohort were picked, and aliquots then underwent multiomic analyses. 

Offering his perspective on the new product, Sudhir K. Dutta, MBBS, associate professor in the Division of Gastroenterology and Hepatology at Johns Hopkins University School of Medicine, Baltimore, said, “This tool will be 100% useful for microbiome research.”

And according to Lori Holtz, MD, MSPH, professor of pediatric gastroenterology, hepatology, and nutrition at Washington University School of Medicine in St. Louis, Missouri, the material will aid microbiome research by allowing interpretability and repeatability across studies. “Microbiome research is a relatively new field, and protocols differ from group to group and lab to lab, so it’s been difficult to compare results across studies,” she told GI & Hepatology News. “A standard stool product will allow for greater comparability in preclinical studies and later clinical trials testing interventions to alter the microbiome.”

The NIST developers are looking forward to reaction from the GI research community. “Over the last several years, we’ve released smaller pilot batches of material to smaller groups of stakeholders,” said Jackson. “We’ve used the feedback on these earlier batches to inform the manufacturing and characterization of the final batch that was released in March, but we don’t yet have any feedback yet on the current material.”

Dr. Lori Holtz



Jackson, Dutta, and Holtz disclosed having no relevant competing interests.

A version of this article appeared on Medscape.com.

The US National Institute of Standards and Technology (NIST) has developed precisely measured human fecal material to foster a new era in gut microbiome research. 

Scott A. Jackson

According to AGA’s Center for Gut Microbiome Research & Education, this critical resource will help advance the utility and reproducibility of microbiome-based diagnostics — “which still remain relatively meaningless clinically, although patients continue to buy direct-to-consumer tests, and a standard reference material will mean there’s a better way to ensure quality control and accuracy.” 

Though not a therapeutic, Human Fecal Material RM is expected to speed up gastrointestinal (GI) therapeutics since many microbiome-based drugs are inspired by fecal transplants with human stool as the developmental starting point. A standardized reference material will be an important resource as industry develops and tests new drugs. It can be purchased online at the NIST Store (shop.nist.gov).

The product consists of eight frozen vials of exhaustively studied human feces suspended in aqueous solution. Available are more than 25 pages of data identifying the key microbes and biomolecules in the material. Scientists, including those working at biopharmaceutical and biotech companies, can use this material to further their research and develop new drugs that target the microbiome, including treatments that contain living bacteria. 

 

Development

According to NIST, the stool material is “the most precisely measured, scientifically analyzed, and richly characterized human fecal standard ever produced. 

“The project ran for about 6 years from start to finish, the last 2 for manufacturing, characterization, and writing,” said NIST molecular geneticist Scott A. Jackson, PhD, who helped develop the product. “We hope our reference material will lay the foundation for gut microbiome research to thrive and reach its full potential.” 

Dr. Sudhir K. Dutta


As founder of NIST’s Complex Microbial Systems Group, Jackson is leading international efforts to improve microbiome and metagenomic measurements by organizing inter-lab studies and refining reference materials and methods. 

The project collected stool from two cohorts of donors, ie, vegetarians and omnivores, with each cohort comprising four to six donors. Material from each cohort was pooled and homogenized before being aliquoted into 5000 vials per cohort. About 300 tubes from each cohort were picked, and aliquots then underwent multiomic analyses. 

Offering his perspective on the new product, Sudhir K. Dutta, MBBS, associate professor in the Division of Gastroenterology and Hepatology at Johns Hopkins University School of Medicine, Baltimore, said, “This tool will be 100% useful for microbiome research.”

And according to Lori Holtz, MD, MSPH, professor of pediatric gastroenterology, hepatology, and nutrition at Washington University School of Medicine in St. Louis, Missouri, the material will aid microbiome research by allowing interpretability and repeatability across studies. “Microbiome research is a relatively new field, and protocols differ from group to group and lab to lab, so it’s been difficult to compare results across studies,” she told GI & Hepatology News. “A standard stool product will allow for greater comparability in preclinical studies and later clinical trials testing interventions to alter the microbiome.”

The NIST developers are looking forward to reaction from the GI research community. “Over the last several years, we’ve released smaller pilot batches of material to smaller groups of stakeholders,” said Jackson. “We’ve used the feedback on these earlier batches to inform the manufacturing and characterization of the final batch that was released in March, but we don’t yet have any feedback yet on the current material.”

Dr. Lori Holtz



Jackson, Dutta, and Holtz disclosed having no relevant competing interests.

A version of this article appeared on Medscape.com.

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Auto-Brewery Syndrome Explained: New Patient Cohort Identifies Culprit Bacteria, Fermentation

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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 research on this cohort has confirmed excess ethanol production — and elevations of both proteobacteria and fermentation pathways — in patients whose ABS symptoms had flared.

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.

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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 research on this cohort has confirmed excess ethanol production — and elevations of both proteobacteria and fermentation pathways — in patients whose ABS symptoms had flared.

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 research on this cohort has confirmed excess ethanol production — and elevations of both proteobacteria and fermentation pathways — in patients whose ABS symptoms had flared.

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.

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Elemental Diet Eases Symptoms in Microbiome Gastro Disorders

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Short-term adherence to a palatable elemental diet (PED) significantly improved symptoms and the gut microbiota in adults with microbiome-driven gastrointestinal disorders, according to a new study.

Dr. Ali Rezaie

“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.

Dr. Jatin Roper

“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.

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Short-term adherence to a palatable elemental diet (PED) significantly improved symptoms and the gut microbiota in adults with microbiome-driven gastrointestinal disorders, according to a new study.

Dr. Ali Rezaie

“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.

Dr. Jatin Roper

“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.

Short-term adherence to a palatable elemental diet (PED) significantly improved symptoms and the gut microbiota in adults with microbiome-driven gastrointestinal disorders, according to a new study.

Dr. Ali Rezaie

“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.

Dr. Jatin Roper

“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.

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The Extra-Bacterial Gut Ecosystem: The Influence of Phages and Fungi in the Microbiome

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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: How can phages be used to manipulate the gut microbiome and influence GI-related diseases? And how can the pathogenic potential of commensal fungi be limited?

 

‘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.”

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.

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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: How can phages be used to manipulate the gut microbiome and influence GI-related diseases? And how can the pathogenic potential of commensal fungi be limited?

 

‘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.”

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: How can phages be used to manipulate the gut microbiome and influence GI-related diseases? And how can the pathogenic potential of commensal fungi be limited?

 

‘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.”

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.

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Wearable Devices May Predict IBD Flares Weeks in Advance

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Wearable devices like the Apple Watch and Fitbit may help identify and predict inflammatory bowel disease (IBD) flares, and even distinguish between inflammatory and purely symptomatic episodes, 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.

 

Dr. Robert P. Hirten

“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.

 

Body

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.”

Dr. Dana J. Lukin



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.

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Body

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.”

Dr. Dana J. Lukin



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.

Body

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.”

Dr. Dana J. Lukin



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.

Title
Key Takeaways
Key Takeaways

Wearable devices like the Apple Watch and Fitbit may help identify and predict inflammatory bowel disease (IBD) flares, and even distinguish between inflammatory and purely symptomatic episodes, 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.

 

Dr. Robert P. Hirten

“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.

 

Wearable devices like the Apple Watch and Fitbit may help identify and predict inflammatory bowel disease (IBD) flares, and even distinguish between inflammatory and purely symptomatic episodes, 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.

 

Dr. Robert P. Hirten

“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.

 

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Gut Microbiome Influences Multiple Neurodegenerative Disorders

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Thu, 04/03/2025 - 14:45

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.

Andrea R. Merchak

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.

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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.

Andrea R. Merchak

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.

Andrea R. Merchak

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.

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FDA OKs Guselkumab for Crohn’s Disease

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The United States Food and Drug Administration (FDA) approved guselkumab (Tremfya, Johnson & Johnson) for the treatment of adults with moderately to severely active Crohn’s disease (CD).

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.

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The United States Food and Drug Administration (FDA) approved guselkumab (Tremfya, Johnson & Johnson) for the treatment of adults with moderately to severely active Crohn’s disease (CD).

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 United States Food and Drug Administration (FDA) approved guselkumab (Tremfya, Johnson & Johnson) for the treatment of adults with moderately to severely active Crohn’s disease (CD).

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.

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