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Withdrawing Anti-TNF in IBD Remission: New Data
In the Spanish EXIT study, anti-TNF withdrawal in selected patients with IBD in clinical, endoscopic, and radiological remission had no impact on sustained clinical remission at 1 year, although objective markers of activity were higher in patients who stopped treatment.
The discontinuation of anti-TNF treatment “could be considered as an option” for a selected group of patients, said the authors led by Javier Gisbert, MD, PhD, with Autonomous University of Madrid.
However, the higher proportion of patients with elevated fecal calprotectin and significant endoscopic lesions at the end of follow-up “calls for caution and should be considered when discontinuing treatment in patients,” Gisbert and colleagues concluded.
The EXIT study results were published in the journal Gut (2025 Feb. doi: 10.1136/gutjnl-2024-333385).
Risky Business?
Anti-TNF drugs have reshaped IBD treatment but bring infection risks and costs, prompting interest in planned withdrawal after stable remission.
Yet prior evidence has been mixed. A meta-analysis of 27 studies suggested higher relapse after stopping anti-TNF therapy. However, the results were heterogeneous and most of the studies were retrospective, with a low number of patients and without a control group to compare with.
Clinical trials that have assessed the risk for relapse after discontinuation of anti-TNF therapy generally favored maintenance but had notable limitations.
The EXIT trial was conducted at 33 IBD units across Spain. A total of 140 patients in steroid-free clinical remission for ≥ 6 months on standard-dose infliximab or adalimumab were randomized (1:1) to either continue anti-TNF or switch to placebo matched to the drug they had been taking. All patients continued on immunomodulator therapy.
At 1 year, the proportion of patients with sustained clinical remission (primary outcome) was similar between patients who continued anti-TNF therapy and peers who stopped the medication (76% and 84%, respectively).
However, the proportion of patients with significant endoscopic lesions at the end of follow-up was higher in those who withdrew anti-TNF therapy (19% vs 8.5%; P = .01). Elevated fecal calprotectin (> 250 µg/g) was more common after withdrawal (33% vs 13%; P = .01).
Fecal calprotectin > 250 µg/g at baseline predicted lower odds of sustained remission and higher risk for losing remission — and was the only factor associated with lower likelihood of sustained remission.
Common Clinical Question
“When a patient starts an advanced biologic therapy, they often ask — will I be able to stop it?” Jean-Frederic Colombel, MD, director of the Inflammatory Bowel Disease Clinical Center at the Icahn School of Medicine at Mount Sinai, New York City, who wasn’t involved in the study, told GI & Hepatology News.
Generally speaking, Colombel said he tells patients, “If the drug is working well and you are in deep remission, they should try to avoid stopping because there is a risk of relapse. And with relapse, we never know if the drug will work again and maybe we’ll have to switch to another medication.”
“It’s an individualized discussion and decision and patients who do opt to stop [anti-TNF therapy] need to be monitored closely,” Colombel said.
Colombel cautioned that the study had a relatively short 1-year follow-up and those that stopped anti-TNF therapy had evidence of recurrent inflammation.
“Even though it didn’t translate yet to clinical relapse, there were more patients with subclinical active disease in the group that stopped as compared to the group that continued,” Colombel said.
He also noted that in the SPARE trial of patients with Crohn’s disease in clinical remission, patients who stopped infliximab had a higher risk for relapse compared with patients who stopped azathioprine and those who continued the combination therapy.
The EXIT study was supported by grants from Instituto de Salud Carlos III, Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa and AbbVie. Gisbert reported serving as speaker, consultant, and advisory member for or receiving research funding from MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma. Colombel had no relevant disclosures.
A version of this article appeared on Medscape.com.
In the Spanish EXIT study, anti-TNF withdrawal in selected patients with IBD in clinical, endoscopic, and radiological remission had no impact on sustained clinical remission at 1 year, although objective markers of activity were higher in patients who stopped treatment.
The discontinuation of anti-TNF treatment “could be considered as an option” for a selected group of patients, said the authors led by Javier Gisbert, MD, PhD, with Autonomous University of Madrid.
However, the higher proportion of patients with elevated fecal calprotectin and significant endoscopic lesions at the end of follow-up “calls for caution and should be considered when discontinuing treatment in patients,” Gisbert and colleagues concluded.
The EXIT study results were published in the journal Gut (2025 Feb. doi: 10.1136/gutjnl-2024-333385).
Risky Business?
Anti-TNF drugs have reshaped IBD treatment but bring infection risks and costs, prompting interest in planned withdrawal after stable remission.
Yet prior evidence has been mixed. A meta-analysis of 27 studies suggested higher relapse after stopping anti-TNF therapy. However, the results were heterogeneous and most of the studies were retrospective, with a low number of patients and without a control group to compare with.
Clinical trials that have assessed the risk for relapse after discontinuation of anti-TNF therapy generally favored maintenance but had notable limitations.
The EXIT trial was conducted at 33 IBD units across Spain. A total of 140 patients in steroid-free clinical remission for ≥ 6 months on standard-dose infliximab or adalimumab were randomized (1:1) to either continue anti-TNF or switch to placebo matched to the drug they had been taking. All patients continued on immunomodulator therapy.
At 1 year, the proportion of patients with sustained clinical remission (primary outcome) was similar between patients who continued anti-TNF therapy and peers who stopped the medication (76% and 84%, respectively).
However, the proportion of patients with significant endoscopic lesions at the end of follow-up was higher in those who withdrew anti-TNF therapy (19% vs 8.5%; P = .01). Elevated fecal calprotectin (> 250 µg/g) was more common after withdrawal (33% vs 13%; P = .01).
Fecal calprotectin > 250 µg/g at baseline predicted lower odds of sustained remission and higher risk for losing remission — and was the only factor associated with lower likelihood of sustained remission.
Common Clinical Question
“When a patient starts an advanced biologic therapy, they often ask — will I be able to stop it?” Jean-Frederic Colombel, MD, director of the Inflammatory Bowel Disease Clinical Center at the Icahn School of Medicine at Mount Sinai, New York City, who wasn’t involved in the study, told GI & Hepatology News.
Generally speaking, Colombel said he tells patients, “If the drug is working well and you are in deep remission, they should try to avoid stopping because there is a risk of relapse. And with relapse, we never know if the drug will work again and maybe we’ll have to switch to another medication.”
“It’s an individualized discussion and decision and patients who do opt to stop [anti-TNF therapy] need to be monitored closely,” Colombel said.
Colombel cautioned that the study had a relatively short 1-year follow-up and those that stopped anti-TNF therapy had evidence of recurrent inflammation.
“Even though it didn’t translate yet to clinical relapse, there were more patients with subclinical active disease in the group that stopped as compared to the group that continued,” Colombel said.
He also noted that in the SPARE trial of patients with Crohn’s disease in clinical remission, patients who stopped infliximab had a higher risk for relapse compared with patients who stopped azathioprine and those who continued the combination therapy.
The EXIT study was supported by grants from Instituto de Salud Carlos III, Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa and AbbVie. Gisbert reported serving as speaker, consultant, and advisory member for or receiving research funding from MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma. Colombel had no relevant disclosures.
A version of this article appeared on Medscape.com.
In the Spanish EXIT study, anti-TNF withdrawal in selected patients with IBD in clinical, endoscopic, and radiological remission had no impact on sustained clinical remission at 1 year, although objective markers of activity were higher in patients who stopped treatment.
The discontinuation of anti-TNF treatment “could be considered as an option” for a selected group of patients, said the authors led by Javier Gisbert, MD, PhD, with Autonomous University of Madrid.
However, the higher proportion of patients with elevated fecal calprotectin and significant endoscopic lesions at the end of follow-up “calls for caution and should be considered when discontinuing treatment in patients,” Gisbert and colleagues concluded.
The EXIT study results were published in the journal Gut (2025 Feb. doi: 10.1136/gutjnl-2024-333385).
Risky Business?
Anti-TNF drugs have reshaped IBD treatment but bring infection risks and costs, prompting interest in planned withdrawal after stable remission.
Yet prior evidence has been mixed. A meta-analysis of 27 studies suggested higher relapse after stopping anti-TNF therapy. However, the results were heterogeneous and most of the studies were retrospective, with a low number of patients and without a control group to compare with.
Clinical trials that have assessed the risk for relapse after discontinuation of anti-TNF therapy generally favored maintenance but had notable limitations.
The EXIT trial was conducted at 33 IBD units across Spain. A total of 140 patients in steroid-free clinical remission for ≥ 6 months on standard-dose infliximab or adalimumab were randomized (1:1) to either continue anti-TNF or switch to placebo matched to the drug they had been taking. All patients continued on immunomodulator therapy.
At 1 year, the proportion of patients with sustained clinical remission (primary outcome) was similar between patients who continued anti-TNF therapy and peers who stopped the medication (76% and 84%, respectively).
However, the proportion of patients with significant endoscopic lesions at the end of follow-up was higher in those who withdrew anti-TNF therapy (19% vs 8.5%; P = .01). Elevated fecal calprotectin (> 250 µg/g) was more common after withdrawal (33% vs 13%; P = .01).
Fecal calprotectin > 250 µg/g at baseline predicted lower odds of sustained remission and higher risk for losing remission — and was the only factor associated with lower likelihood of sustained remission.
Common Clinical Question
“When a patient starts an advanced biologic therapy, they often ask — will I be able to stop it?” Jean-Frederic Colombel, MD, director of the Inflammatory Bowel Disease Clinical Center at the Icahn School of Medicine at Mount Sinai, New York City, who wasn’t involved in the study, told GI & Hepatology News.
Generally speaking, Colombel said he tells patients, “If the drug is working well and you are in deep remission, they should try to avoid stopping because there is a risk of relapse. And with relapse, we never know if the drug will work again and maybe we’ll have to switch to another medication.”
“It’s an individualized discussion and decision and patients who do opt to stop [anti-TNF therapy] need to be monitored closely,” Colombel said.
Colombel cautioned that the study had a relatively short 1-year follow-up and those that stopped anti-TNF therapy had evidence of recurrent inflammation.
“Even though it didn’t translate yet to clinical relapse, there were more patients with subclinical active disease in the group that stopped as compared to the group that continued,” Colombel said.
He also noted that in the SPARE trial of patients with Crohn’s disease in clinical remission, patients who stopped infliximab had a higher risk for relapse compared with patients who stopped azathioprine and those who continued the combination therapy.
The EXIT study was supported by grants from Instituto de Salud Carlos III, Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa and AbbVie. Gisbert reported serving as speaker, consultant, and advisory member for or receiving research funding from MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma. Colombel had no relevant disclosures.
A version of this article appeared on Medscape.com.
How Chronic Stress Disrupts the Gut Microbiome
Chronic psychological stress is common. A 2023 survey revealed that about one quarter of US adults reported high stress levels, and three quarters reported that chronic stress affects their daily lives.
Emerging evidence suggests that chronic stress not only exacts a high toll on mental health but also can wreak havoc on all levels of gastrointestinal (GI) functioning, all the way down to the microbiome.
Aasma Shaukat, MD, MPH, AGAF, gastroenterologist with NYU Langone Health and director of GI Outcomes Research, Gastroenterology at NYU Grossman School of Medicine in New York City, said in an interview with GI & Hepatology News.
“This basically means that the normal balance of microorganisms that essentially we think are beneficial gets reduced, and the colonies considered to be more harmful proliferate,” she explained.
What Does the Science Tell Us?
Numerous studies published in the past 5 years have linked chronic stress to modest but reproducible shifts in the composition of the microbiome.
A study of frontline healthcare workers during COVID-19 revealed that the pandemic was associated with significant depression, anxiety, and stress, as well as gut dysbiosis that persisted for at least half a year.
Notably, healthcare workers had low gut alpha diversity, indicating a less resilient and diverse microbiome, a state often associated with dysbiosis and increased risk for various diseases and negative health outcomes.
A two-cohort study of healthy adults found higher alpha diversity in those reporting low stress levels. It also found a link between stress and enriched levels of Escherichia/Shigella, an overgrowth of which has been linked to various conditions, including inflammatory bowel disease.
In addition, a 2023 systematic review of human studies concluded that stress is associated with changes in specific genera — namely reductions in gut-healthy Lachnospira/Lachnospiraceae and Phascolarctobacterium, which produce beneficial short-chain fatty acids that support the health of the intestinal lining and modulate the immune system.
Stress during specific life stages also appears to alter the gut microbiome.
For example, in a study of postpartum women, those at an increased risk for parenting stress showed lower alpha diversity on the Shannon diversity index.
Research involving mother-child pairs tied adversity — such as maltreatment of the mother during her childhood, prenatal anxiety, and hardship in the child’s early life — to distinct microbiome profiles in 2-year-olds, supporting a stress-microbiome pathway relevant to socioemotional outcomes, the authors said.
Emerging evidence indicates a link between the gut microbiome and posttraumatic stress disorder (PTSD).
A recent systematic review found differences in gut microbial taxa between individuals with PTSD and trauma-exposed controls without PTSD. A separate analysis pointed to a potential causal impact of gut microbiomes on the development of PTSD.
Mechanisms Behind the Link
Stress interferes with the brain’s production of neurotransmitters, such as serotonin, which controls anxiety, mood, sleep, and many other functions in the brain, Shaukat told GI & Hepatology News.
“But serotonin also crosses the blood-brain barrier, and actually, the gut has more serotonin receptors than the brain, so an imbalance of serotonin can actually affect the gut microbiome through signaling at the neurotransmitter level,” Shaukat explained.
Stress can also affect sleep, and sleep itself has regulatory properties for gut bacteria, Shaukat noted.
“Stress also lowers our immunity, and this can make the gut barrier susceptible or permeable to bacterial toxins that can pass through and breach the gut barrier and be released into the bloodstream, which can trigger inflammation,” Shaukat explained.
Implications for Patient Care
The gut-brain-microbiome axis remains an emerging field of study. “We’re learning more and more about this, and we need to because the microbial colonies are so diverse and we haven’t nailed it down yet,” Shaukat said.
In the meantime, what can clinicians tell patients?
Aside from managing stress, which “is easier said than done,” patients can improve their diet, Shaukat said.
“What we tell patients is to essentially increase their intake of gut-friendly foods that preferentially grow the bacterial colonies that are beneficial for us,” Shaukat said. This includes fermented foods, yogurt, kimchi, chia seeds, kombucha, pickled vegetables, and whole grains.
A recent randomized controlled trial of healthy adults found a “psychobiotic diet” — a diet high in prebiotic and fermented foods — was associated with less perceived stress and subtle beneficial shifts in microbial composition.
“These foods can help keep the gut in good health and may actually also reduce or mitigate some of the effects of stress,” Shaukat said.
“Eating well is something I think we should all think about and maybe prioritize when we’re going through a stressful situation or looking to kind of mitigate the effects of stress and the anxiety and depression it can cause,” she advised.
Shaukat said she also encourages patients to engage in regular physical activity, which benefits the gut microbiome by helping to regulate gut motility. Exercise can also boost mood and help relieve stress.
“A balanced Mediterranean diet and regular activity is truly the secret for gut health,” Shaukat said.
Patients may be tempted by the probiotic supplements lining drugstore shelves, but there “isn’t great evidence for probiotic supplements,” she said. “What we can get from dietary sources far outweighs what can be put in a pill.”
Shaukat disclosed having no relevant disclosures.
A version of this article appeared on Medscape.com.
Chronic psychological stress is common. A 2023 survey revealed that about one quarter of US adults reported high stress levels, and three quarters reported that chronic stress affects their daily lives.
Emerging evidence suggests that chronic stress not only exacts a high toll on mental health but also can wreak havoc on all levels of gastrointestinal (GI) functioning, all the way down to the microbiome.
Aasma Shaukat, MD, MPH, AGAF, gastroenterologist with NYU Langone Health and director of GI Outcomes Research, Gastroenterology at NYU Grossman School of Medicine in New York City, said in an interview with GI & Hepatology News.
“This basically means that the normal balance of microorganisms that essentially we think are beneficial gets reduced, and the colonies considered to be more harmful proliferate,” she explained.
What Does the Science Tell Us?
Numerous studies published in the past 5 years have linked chronic stress to modest but reproducible shifts in the composition of the microbiome.
A study of frontline healthcare workers during COVID-19 revealed that the pandemic was associated with significant depression, anxiety, and stress, as well as gut dysbiosis that persisted for at least half a year.
Notably, healthcare workers had low gut alpha diversity, indicating a less resilient and diverse microbiome, a state often associated with dysbiosis and increased risk for various diseases and negative health outcomes.
A two-cohort study of healthy adults found higher alpha diversity in those reporting low stress levels. It also found a link between stress and enriched levels of Escherichia/Shigella, an overgrowth of which has been linked to various conditions, including inflammatory bowel disease.
In addition, a 2023 systematic review of human studies concluded that stress is associated with changes in specific genera — namely reductions in gut-healthy Lachnospira/Lachnospiraceae and Phascolarctobacterium, which produce beneficial short-chain fatty acids that support the health of the intestinal lining and modulate the immune system.
Stress during specific life stages also appears to alter the gut microbiome.
For example, in a study of postpartum women, those at an increased risk for parenting stress showed lower alpha diversity on the Shannon diversity index.
Research involving mother-child pairs tied adversity — such as maltreatment of the mother during her childhood, prenatal anxiety, and hardship in the child’s early life — to distinct microbiome profiles in 2-year-olds, supporting a stress-microbiome pathway relevant to socioemotional outcomes, the authors said.
Emerging evidence indicates a link between the gut microbiome and posttraumatic stress disorder (PTSD).
A recent systematic review found differences in gut microbial taxa between individuals with PTSD and trauma-exposed controls without PTSD. A separate analysis pointed to a potential causal impact of gut microbiomes on the development of PTSD.
Mechanisms Behind the Link
Stress interferes with the brain’s production of neurotransmitters, such as serotonin, which controls anxiety, mood, sleep, and many other functions in the brain, Shaukat told GI & Hepatology News.
“But serotonin also crosses the blood-brain barrier, and actually, the gut has more serotonin receptors than the brain, so an imbalance of serotonin can actually affect the gut microbiome through signaling at the neurotransmitter level,” Shaukat explained.
Stress can also affect sleep, and sleep itself has regulatory properties for gut bacteria, Shaukat noted.
“Stress also lowers our immunity, and this can make the gut barrier susceptible or permeable to bacterial toxins that can pass through and breach the gut barrier and be released into the bloodstream, which can trigger inflammation,” Shaukat explained.
Implications for Patient Care
The gut-brain-microbiome axis remains an emerging field of study. “We’re learning more and more about this, and we need to because the microbial colonies are so diverse and we haven’t nailed it down yet,” Shaukat said.
In the meantime, what can clinicians tell patients?
Aside from managing stress, which “is easier said than done,” patients can improve their diet, Shaukat said.
“What we tell patients is to essentially increase their intake of gut-friendly foods that preferentially grow the bacterial colonies that are beneficial for us,” Shaukat said. This includes fermented foods, yogurt, kimchi, chia seeds, kombucha, pickled vegetables, and whole grains.
A recent randomized controlled trial of healthy adults found a “psychobiotic diet” — a diet high in prebiotic and fermented foods — was associated with less perceived stress and subtle beneficial shifts in microbial composition.
“These foods can help keep the gut in good health and may actually also reduce or mitigate some of the effects of stress,” Shaukat said.
“Eating well is something I think we should all think about and maybe prioritize when we’re going through a stressful situation or looking to kind of mitigate the effects of stress and the anxiety and depression it can cause,” she advised.
Shaukat said she also encourages patients to engage in regular physical activity, which benefits the gut microbiome by helping to regulate gut motility. Exercise can also boost mood and help relieve stress.
“A balanced Mediterranean diet and regular activity is truly the secret for gut health,” Shaukat said.
Patients may be tempted by the probiotic supplements lining drugstore shelves, but there “isn’t great evidence for probiotic supplements,” she said. “What we can get from dietary sources far outweighs what can be put in a pill.”
Shaukat disclosed having no relevant disclosures.
A version of this article appeared on Medscape.com.
Chronic psychological stress is common. A 2023 survey revealed that about one quarter of US adults reported high stress levels, and three quarters reported that chronic stress affects their daily lives.
Emerging evidence suggests that chronic stress not only exacts a high toll on mental health but also can wreak havoc on all levels of gastrointestinal (GI) functioning, all the way down to the microbiome.
Aasma Shaukat, MD, MPH, AGAF, gastroenterologist with NYU Langone Health and director of GI Outcomes Research, Gastroenterology at NYU Grossman School of Medicine in New York City, said in an interview with GI & Hepatology News.
“This basically means that the normal balance of microorganisms that essentially we think are beneficial gets reduced, and the colonies considered to be more harmful proliferate,” she explained.
What Does the Science Tell Us?
Numerous studies published in the past 5 years have linked chronic stress to modest but reproducible shifts in the composition of the microbiome.
A study of frontline healthcare workers during COVID-19 revealed that the pandemic was associated with significant depression, anxiety, and stress, as well as gut dysbiosis that persisted for at least half a year.
Notably, healthcare workers had low gut alpha diversity, indicating a less resilient and diverse microbiome, a state often associated with dysbiosis and increased risk for various diseases and negative health outcomes.
A two-cohort study of healthy adults found higher alpha diversity in those reporting low stress levels. It also found a link between stress and enriched levels of Escherichia/Shigella, an overgrowth of which has been linked to various conditions, including inflammatory bowel disease.
In addition, a 2023 systematic review of human studies concluded that stress is associated with changes in specific genera — namely reductions in gut-healthy Lachnospira/Lachnospiraceae and Phascolarctobacterium, which produce beneficial short-chain fatty acids that support the health of the intestinal lining and modulate the immune system.
Stress during specific life stages also appears to alter the gut microbiome.
For example, in a study of postpartum women, those at an increased risk for parenting stress showed lower alpha diversity on the Shannon diversity index.
Research involving mother-child pairs tied adversity — such as maltreatment of the mother during her childhood, prenatal anxiety, and hardship in the child’s early life — to distinct microbiome profiles in 2-year-olds, supporting a stress-microbiome pathway relevant to socioemotional outcomes, the authors said.
Emerging evidence indicates a link between the gut microbiome and posttraumatic stress disorder (PTSD).
A recent systematic review found differences in gut microbial taxa between individuals with PTSD and trauma-exposed controls without PTSD. A separate analysis pointed to a potential causal impact of gut microbiomes on the development of PTSD.
Mechanisms Behind the Link
Stress interferes with the brain’s production of neurotransmitters, such as serotonin, which controls anxiety, mood, sleep, and many other functions in the brain, Shaukat told GI & Hepatology News.
“But serotonin also crosses the blood-brain barrier, and actually, the gut has more serotonin receptors than the brain, so an imbalance of serotonin can actually affect the gut microbiome through signaling at the neurotransmitter level,” Shaukat explained.
Stress can also affect sleep, and sleep itself has regulatory properties for gut bacteria, Shaukat noted.
“Stress also lowers our immunity, and this can make the gut barrier susceptible or permeable to bacterial toxins that can pass through and breach the gut barrier and be released into the bloodstream, which can trigger inflammation,” Shaukat explained.
Implications for Patient Care
The gut-brain-microbiome axis remains an emerging field of study. “We’re learning more and more about this, and we need to because the microbial colonies are so diverse and we haven’t nailed it down yet,” Shaukat said.
In the meantime, what can clinicians tell patients?
Aside from managing stress, which “is easier said than done,” patients can improve their diet, Shaukat said.
“What we tell patients is to essentially increase their intake of gut-friendly foods that preferentially grow the bacterial colonies that are beneficial for us,” Shaukat said. This includes fermented foods, yogurt, kimchi, chia seeds, kombucha, pickled vegetables, and whole grains.
A recent randomized controlled trial of healthy adults found a “psychobiotic diet” — a diet high in prebiotic and fermented foods — was associated with less perceived stress and subtle beneficial shifts in microbial composition.
“These foods can help keep the gut in good health and may actually also reduce or mitigate some of the effects of stress,” Shaukat said.
“Eating well is something I think we should all think about and maybe prioritize when we’re going through a stressful situation or looking to kind of mitigate the effects of stress and the anxiety and depression it can cause,” she advised.
Shaukat said she also encourages patients to engage in regular physical activity, which benefits the gut microbiome by helping to regulate gut motility. Exercise can also boost mood and help relieve stress.
“A balanced Mediterranean diet and regular activity is truly the secret for gut health,” Shaukat said.
Patients may be tempted by the probiotic supplements lining drugstore shelves, but there “isn’t great evidence for probiotic supplements,” she said. “What we can get from dietary sources far outweighs what can be put in a pill.”
Shaukat disclosed having no relevant disclosures.
A version of this article appeared on Medscape.com.
IBD 101: Intensive Course for GI Fellows Boosts Clinical Confidence
Results from the initial pilot program in 2019, called “IBD 101: Physicians and Patients Providing Pearls and Perspectives” are outlined in Inflammatory Bowel Diseases by Lisa Malter, MD, AGAF, a professor of medicine in the Division of Gastroenterology at NYU Langone Grossman School of Medicine, New York City, and colleagues.
The course, conducted by Malter at NYU Langone’s simulation center, was designed to increase fellows’ early exposure to the complexities of IBD and its diagnosis and management in the context of rapidly changing therapies and variability across US GI training programs. The authors reported that the 2019 program was well received, with attendees showing “increased comfort and sustained benefit” in discussing IBD management with patients. Notably, participants’ increased comfort levels in broaching IBD topics persisted 3 years after the course compared with that of nonparticipating peers, pointing to potential improved patient care after completion of training.
“At this point, 1 in every 100 GI patients has IBD. It’s one of the more complex GI conditions and its incidence and prevalence are increasing globally,” Malter told GI & Hepatology News. Prevalence rates in the US are reportedly as high as 464.5 per 100,000 persons.
“In addition, its management has become more complicated with newer medications and treatments coming on stream,” she said. “An educational gap exists.”
The Program
The course provided an intimate, interactive format with national experts in the field serving as faculty. Course objectives included basic, introductory information on the diagnosis, treatment, and management of IBD; early exposure to IBD as a subspecialty to allow registrants to make informed career decisions; and information about other educational opportunities.
The course was designed to raise participants’ comfort levels in discussing seven topics with patients, including the need for surgery, IBD in pregnancy, treatment escalation in different disease scenarios, and lack of treatment response.
The three-part course, featuring case scenarios, was offered in person to 60 fellows selected by regional GI fellowship program directors and course faculty, which consisted of a director, three codirectors, and 14 local and national IBD experts. A half-day training session for faculty was held immediately before the course.
In September 2019, the first 32 fellows from Accreditation Council for Graduate Medical Education-accredited programs participated in IBD 101. A total of 49 (89%) of 55 participants completed presession and immediate postsession surveys.
In the 3-year follow-up survey, among 36 fellows, of whom 21 (58%) attended IBD 101 and 15 (42%) did not, attendees reported overall IBD confidence and equivalent or higher levels of comfort in discussing each of seven topics.
Among the specific survey findings:
- 100% said the course had improved their ability to effectively treat and manage patients
- A higher proportion of attendees strongly agreed with having comfort in discussing pregnancy in IBD (43% vs 13%; P = .08)
- A statistically significant proportion strongly agreed with having comfort in discussing loss of response to biologics (62% vs 27%; P = .049)
- 98% reported increased interest in exploring IBD during fellowship
- 100% noted improved understanding of supplemental opportunities to learn about IBD
- 96% would strongly recommend this course to future GI fellows
Further testimony to the effectiveness of the ongoing course, said Malter, is that the version offered in 2024 attracted 425 GI fellows from across the country. “That’s about 90% of US GI fellows,” she said.
Offering an outsider’s perspective on the results of the course, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, a director or the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston, said, “It’s a useful update. It’s always good to see benefits from educational courses.” He expressed caution, however, “in that a small subset of GI fellows always selects toward those with greater IBD interest. Consequently, they likely have participated in several other IBD education activities in the intervening 3 years — so one can’t attribute benefit to this course alone.”
And while one effect of such courses may to increase the number of IBD-interested trainees, their role in providing IBD education to gastroenterologists who will not specialize in IBD is more important, Ananthakrishnan added. “These general gastroenterologists are going to be managing a lot of the IBD in the community, so in my opinion, ensuring they are comfortable with caring for IBD patients optimally is more important than training IBD specialists, who have many opportunities for education.”
In collaboration with the American College of Gastroenterology, the course is open to all first-year GI fellows training in North America. The most recent program was held on September 13, 2025.
This paper received no specific funding. The IBD course has been supported by unrestricted educational grants from Pfizer and Takeda Pharmaceuticals and sponsorships from AbbVie, Janssen, and Prometheus Labs.Malter reported receiving educational grants from AbbVie, Janssen, Pfizer, and Takeda; serving as a consultant for Abbvie and Pharmacosmos; and serving on the advisory boards for AbbVie, Bristol Myers Squibb, Celltrion, Janssen, Merck, and Takeda. Multiple coauthors disclosed similar relationships with numerous private-sector companies.
A version of this article appeared on Medscape.com.
Results from the initial pilot program in 2019, called “IBD 101: Physicians and Patients Providing Pearls and Perspectives” are outlined in Inflammatory Bowel Diseases by Lisa Malter, MD, AGAF, a professor of medicine in the Division of Gastroenterology at NYU Langone Grossman School of Medicine, New York City, and colleagues.
The course, conducted by Malter at NYU Langone’s simulation center, was designed to increase fellows’ early exposure to the complexities of IBD and its diagnosis and management in the context of rapidly changing therapies and variability across US GI training programs. The authors reported that the 2019 program was well received, with attendees showing “increased comfort and sustained benefit” in discussing IBD management with patients. Notably, participants’ increased comfort levels in broaching IBD topics persisted 3 years after the course compared with that of nonparticipating peers, pointing to potential improved patient care after completion of training.
“At this point, 1 in every 100 GI patients has IBD. It’s one of the more complex GI conditions and its incidence and prevalence are increasing globally,” Malter told GI & Hepatology News. Prevalence rates in the US are reportedly as high as 464.5 per 100,000 persons.
“In addition, its management has become more complicated with newer medications and treatments coming on stream,” she said. “An educational gap exists.”
The Program
The course provided an intimate, interactive format with national experts in the field serving as faculty. Course objectives included basic, introductory information on the diagnosis, treatment, and management of IBD; early exposure to IBD as a subspecialty to allow registrants to make informed career decisions; and information about other educational opportunities.
The course was designed to raise participants’ comfort levels in discussing seven topics with patients, including the need for surgery, IBD in pregnancy, treatment escalation in different disease scenarios, and lack of treatment response.
The three-part course, featuring case scenarios, was offered in person to 60 fellows selected by regional GI fellowship program directors and course faculty, which consisted of a director, three codirectors, and 14 local and national IBD experts. A half-day training session for faculty was held immediately before the course.
In September 2019, the first 32 fellows from Accreditation Council for Graduate Medical Education-accredited programs participated in IBD 101. A total of 49 (89%) of 55 participants completed presession and immediate postsession surveys.
In the 3-year follow-up survey, among 36 fellows, of whom 21 (58%) attended IBD 101 and 15 (42%) did not, attendees reported overall IBD confidence and equivalent or higher levels of comfort in discussing each of seven topics.
Among the specific survey findings:
- 100% said the course had improved their ability to effectively treat and manage patients
- A higher proportion of attendees strongly agreed with having comfort in discussing pregnancy in IBD (43% vs 13%; P = .08)
- A statistically significant proportion strongly agreed with having comfort in discussing loss of response to biologics (62% vs 27%; P = .049)
- 98% reported increased interest in exploring IBD during fellowship
- 100% noted improved understanding of supplemental opportunities to learn about IBD
- 96% would strongly recommend this course to future GI fellows
Further testimony to the effectiveness of the ongoing course, said Malter, is that the version offered in 2024 attracted 425 GI fellows from across the country. “That’s about 90% of US GI fellows,” she said.
Offering an outsider’s perspective on the results of the course, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, a director or the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston, said, “It’s a useful update. It’s always good to see benefits from educational courses.” He expressed caution, however, “in that a small subset of GI fellows always selects toward those with greater IBD interest. Consequently, they likely have participated in several other IBD education activities in the intervening 3 years — so one can’t attribute benefit to this course alone.”
And while one effect of such courses may to increase the number of IBD-interested trainees, their role in providing IBD education to gastroenterologists who will not specialize in IBD is more important, Ananthakrishnan added. “These general gastroenterologists are going to be managing a lot of the IBD in the community, so in my opinion, ensuring they are comfortable with caring for IBD patients optimally is more important than training IBD specialists, who have many opportunities for education.”
In collaboration with the American College of Gastroenterology, the course is open to all first-year GI fellows training in North America. The most recent program was held on September 13, 2025.
This paper received no specific funding. The IBD course has been supported by unrestricted educational grants from Pfizer and Takeda Pharmaceuticals and sponsorships from AbbVie, Janssen, and Prometheus Labs.Malter reported receiving educational grants from AbbVie, Janssen, Pfizer, and Takeda; serving as a consultant for Abbvie and Pharmacosmos; and serving on the advisory boards for AbbVie, Bristol Myers Squibb, Celltrion, Janssen, Merck, and Takeda. Multiple coauthors disclosed similar relationships with numerous private-sector companies.
A version of this article appeared on Medscape.com.
Results from the initial pilot program in 2019, called “IBD 101: Physicians and Patients Providing Pearls and Perspectives” are outlined in Inflammatory Bowel Diseases by Lisa Malter, MD, AGAF, a professor of medicine in the Division of Gastroenterology at NYU Langone Grossman School of Medicine, New York City, and colleagues.
The course, conducted by Malter at NYU Langone’s simulation center, was designed to increase fellows’ early exposure to the complexities of IBD and its diagnosis and management in the context of rapidly changing therapies and variability across US GI training programs. The authors reported that the 2019 program was well received, with attendees showing “increased comfort and sustained benefit” in discussing IBD management with patients. Notably, participants’ increased comfort levels in broaching IBD topics persisted 3 years after the course compared with that of nonparticipating peers, pointing to potential improved patient care after completion of training.
“At this point, 1 in every 100 GI patients has IBD. It’s one of the more complex GI conditions and its incidence and prevalence are increasing globally,” Malter told GI & Hepatology News. Prevalence rates in the US are reportedly as high as 464.5 per 100,000 persons.
“In addition, its management has become more complicated with newer medications and treatments coming on stream,” she said. “An educational gap exists.”
The Program
The course provided an intimate, interactive format with national experts in the field serving as faculty. Course objectives included basic, introductory information on the diagnosis, treatment, and management of IBD; early exposure to IBD as a subspecialty to allow registrants to make informed career decisions; and information about other educational opportunities.
The course was designed to raise participants’ comfort levels in discussing seven topics with patients, including the need for surgery, IBD in pregnancy, treatment escalation in different disease scenarios, and lack of treatment response.
The three-part course, featuring case scenarios, was offered in person to 60 fellows selected by regional GI fellowship program directors and course faculty, which consisted of a director, three codirectors, and 14 local and national IBD experts. A half-day training session for faculty was held immediately before the course.
In September 2019, the first 32 fellows from Accreditation Council for Graduate Medical Education-accredited programs participated in IBD 101. A total of 49 (89%) of 55 participants completed presession and immediate postsession surveys.
In the 3-year follow-up survey, among 36 fellows, of whom 21 (58%) attended IBD 101 and 15 (42%) did not, attendees reported overall IBD confidence and equivalent or higher levels of comfort in discussing each of seven topics.
Among the specific survey findings:
- 100% said the course had improved their ability to effectively treat and manage patients
- A higher proportion of attendees strongly agreed with having comfort in discussing pregnancy in IBD (43% vs 13%; P = .08)
- A statistically significant proportion strongly agreed with having comfort in discussing loss of response to biologics (62% vs 27%; P = .049)
- 98% reported increased interest in exploring IBD during fellowship
- 100% noted improved understanding of supplemental opportunities to learn about IBD
- 96% would strongly recommend this course to future GI fellows
Further testimony to the effectiveness of the ongoing course, said Malter, is that the version offered in 2024 attracted 425 GI fellows from across the country. “That’s about 90% of US GI fellows,” she said.
Offering an outsider’s perspective on the results of the course, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, a director or the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston, said, “It’s a useful update. It’s always good to see benefits from educational courses.” He expressed caution, however, “in that a small subset of GI fellows always selects toward those with greater IBD interest. Consequently, they likely have participated in several other IBD education activities in the intervening 3 years — so one can’t attribute benefit to this course alone.”
And while one effect of such courses may to increase the number of IBD-interested trainees, their role in providing IBD education to gastroenterologists who will not specialize in IBD is more important, Ananthakrishnan added. “These general gastroenterologists are going to be managing a lot of the IBD in the community, so in my opinion, ensuring they are comfortable with caring for IBD patients optimally is more important than training IBD specialists, who have many opportunities for education.”
In collaboration with the American College of Gastroenterology, the course is open to all first-year GI fellows training in North America. The most recent program was held on September 13, 2025.
This paper received no specific funding. The IBD course has been supported by unrestricted educational grants from Pfizer and Takeda Pharmaceuticals and sponsorships from AbbVie, Janssen, and Prometheus Labs.Malter reported receiving educational grants from AbbVie, Janssen, Pfizer, and Takeda; serving as a consultant for Abbvie and Pharmacosmos; and serving on the advisory boards for AbbVie, Bristol Myers Squibb, Celltrion, Janssen, Merck, and Takeda. Multiple coauthors disclosed similar relationships with numerous private-sector companies.
A version of this article appeared on Medscape.com.
FDA OKs Tremfya for Ulcerative Colitis
Guselkumab is the first and only interleukin-23 (IL-23) inhibitor available as both SC and intravenous (IV) induction options for the treatment of UC and Crohn’s disease (CD), the company noted in a news release.
The approval of SC guselkumab induction in UC was based on results from the phase 3 ASTRO trial, which randomly allocated 418 patients with moderately to severely active UC to receive either induction with 400 mg SC guselkumab at weeks 0, 4, and 8 or placebo.
Following induction, the treatment group either received a maintenance dose of 200 mg SC guselkumab at week 12 and then every 4 weeks or 100 mg every 8 weeks (starting at 16 weeks).
All patients had had an inadequate response or intolerance to conventional therapy.
All primary and secondary endpoints demonstrated statistically significant and clinically meaningful improvements with SC guselkumab compared to placebo across all clinical and endoscopic measures, the company said.
At 12 weeks, a significantly greater proportion of patients treated with 400 mg SC guselkumab every 4 weeks achieved clinical remission (26% vs 7% with placebo; P < .001) and endoscopic improvement (36% vs 12%; P < .001).
The results were consistent with the FDA-approved 200 mg IV induction regimen, which previously achieved clinical remission (23% vs 8% with placebo; P < .001) and endoscopic improvement (27% vs 11%; P < .001).
The efficacy of SC and IV induction was comparable across subgroups with severe or refractory disease and both routes demonstrated a similar time to onset of efficacy.
SC guselkumab induction followed by SC guselkumab maintenance therapy also demonstrated statistically significant and clinically meaningful improvements in clinical remission and endoscopic improvement compared to placebo.
“Historically, IL-23 inhibitors have required IV infusions at the start of therapy, which can create barriers to starting treatment or be burdensome for some patients and clinicians,” study investigator David T. Rubin, MD, AGAF, director of the Inflammatory Bowel Disease Center at University of Chicago Medicine, said in the news release.
“UC patients and providers now have the choice of starting Tremfya with a self-administered subcutaneous injection, with the same efficacy and safety that were established with IV induction in the prior clinical trials and subsequently seen in our real-world practice,” Rubin said.
Full prescribing information and medication guide are available online.
A version of this article appeared on Medscape.com.
Guselkumab is the first and only interleukin-23 (IL-23) inhibitor available as both SC and intravenous (IV) induction options for the treatment of UC and Crohn’s disease (CD), the company noted in a news release.
The approval of SC guselkumab induction in UC was based on results from the phase 3 ASTRO trial, which randomly allocated 418 patients with moderately to severely active UC to receive either induction with 400 mg SC guselkumab at weeks 0, 4, and 8 or placebo.
Following induction, the treatment group either received a maintenance dose of 200 mg SC guselkumab at week 12 and then every 4 weeks or 100 mg every 8 weeks (starting at 16 weeks).
All patients had had an inadequate response or intolerance to conventional therapy.
All primary and secondary endpoints demonstrated statistically significant and clinically meaningful improvements with SC guselkumab compared to placebo across all clinical and endoscopic measures, the company said.
At 12 weeks, a significantly greater proportion of patients treated with 400 mg SC guselkumab every 4 weeks achieved clinical remission (26% vs 7% with placebo; P < .001) and endoscopic improvement (36% vs 12%; P < .001).
The results were consistent with the FDA-approved 200 mg IV induction regimen, which previously achieved clinical remission (23% vs 8% with placebo; P < .001) and endoscopic improvement (27% vs 11%; P < .001).
The efficacy of SC and IV induction was comparable across subgroups with severe or refractory disease and both routes demonstrated a similar time to onset of efficacy.
SC guselkumab induction followed by SC guselkumab maintenance therapy also demonstrated statistically significant and clinically meaningful improvements in clinical remission and endoscopic improvement compared to placebo.
“Historically, IL-23 inhibitors have required IV infusions at the start of therapy, which can create barriers to starting treatment or be burdensome for some patients and clinicians,” study investigator David T. Rubin, MD, AGAF, director of the Inflammatory Bowel Disease Center at University of Chicago Medicine, said in the news release.
“UC patients and providers now have the choice of starting Tremfya with a self-administered subcutaneous injection, with the same efficacy and safety that were established with IV induction in the prior clinical trials and subsequently seen in our real-world practice,” Rubin said.
Full prescribing information and medication guide are available online.
A version of this article appeared on Medscape.com.
Guselkumab is the first and only interleukin-23 (IL-23) inhibitor available as both SC and intravenous (IV) induction options for the treatment of UC and Crohn’s disease (CD), the company noted in a news release.
The approval of SC guselkumab induction in UC was based on results from the phase 3 ASTRO trial, which randomly allocated 418 patients with moderately to severely active UC to receive either induction with 400 mg SC guselkumab at weeks 0, 4, and 8 or placebo.
Following induction, the treatment group either received a maintenance dose of 200 mg SC guselkumab at week 12 and then every 4 weeks or 100 mg every 8 weeks (starting at 16 weeks).
All patients had had an inadequate response or intolerance to conventional therapy.
All primary and secondary endpoints demonstrated statistically significant and clinically meaningful improvements with SC guselkumab compared to placebo across all clinical and endoscopic measures, the company said.
At 12 weeks, a significantly greater proportion of patients treated with 400 mg SC guselkumab every 4 weeks achieved clinical remission (26% vs 7% with placebo; P < .001) and endoscopic improvement (36% vs 12%; P < .001).
The results were consistent with the FDA-approved 200 mg IV induction regimen, which previously achieved clinical remission (23% vs 8% with placebo; P < .001) and endoscopic improvement (27% vs 11%; P < .001).
The efficacy of SC and IV induction was comparable across subgroups with severe or refractory disease and both routes demonstrated a similar time to onset of efficacy.
SC guselkumab induction followed by SC guselkumab maintenance therapy also demonstrated statistically significant and clinically meaningful improvements in clinical remission and endoscopic improvement compared to placebo.
“Historically, IL-23 inhibitors have required IV infusions at the start of therapy, which can create barriers to starting treatment or be burdensome for some patients and clinicians,” study investigator David T. Rubin, MD, AGAF, director of the Inflammatory Bowel Disease Center at University of Chicago Medicine, said in the news release.
“UC patients and providers now have the choice of starting Tremfya with a self-administered subcutaneous injection, with the same efficacy and safety that were established with IV induction in the prior clinical trials and subsequently seen in our real-world practice,” Rubin said.
Full prescribing information and medication guide are available online.
A version of this article appeared on Medscape.com.
Could a Clinical Decision Support Tool Improve Outcomes in Pediatric Diarrhea?
“Clinical decision support tools are designed to assist clinicians in making informed and accurate diagnostic and prognostic decisions using available characteristics of the patient and the larger context,” Anna Jones, MD, MPH, and her colleagues wrote in JAMA Network Open.
Jones is in the Department of Pediatrics at the University of Utah School of Medicine in Salt Lake City.
Jones and her coauthors concluded such a tool had the potential to improve evidence-based testing in pediatric diarrhea and help clinicians communicate clearly to parents the etiology of their child’s illness. Parents in the study, however, expressed skepticism over the tool, voicing concerns that physicians might over-rely on its algorithms.
The authors said that thanks to the development of multiplex polymerase chain reaction (PCR) panels for gastroenteritis, it is now possible to quickly identify up to 22 different pathogens from stool samples. What is lacking, they suggested, are protocols for knowing when to test for these pathogens.
“Although the Infectious Diseases Society of America 2017 clinical practice guidelines for the diagnosis and management of infectious diarrhea provide broad recommendations for when diarrhea-related diagnostics should be used, clear guidelines specific to the use of multiplex PCR panels do not exist,” Jones and her coauthors wrote, adding that misusing the diagnostics, however, “can lead to inappropriate antibiotic use and excess financial burdens.”
Meanwhile, communication breakdowns in the patient-doctor relationship are a leading contributor to diagnostic errors, according to the Agency for Healthcare Research and Quality. Subsequently, the National Academy of Medicine has recommended that healthcare professionals seek to engage patients and their families in the diagnostic process.
With these factors in mind, Jones and her colleagues recruited parents who had sought care for their child’s diarrhea and clinicians who routinely treat children with diarrhea. The recruits came from five urgent care sites and one emergency department (ED), all in Utah. Participants were interviewed between June 15, 2023, and January 24, 2025.
In all, the authors interviewed 44 parents (40 women; median age, 34 years). One parent (2%) identified as Asian, two (5%) as Black or African American, 15 (34%) as Hispanic or Latin, and 22 (50%) as White individuals. The remaining four participants (9%) were of unknown race and ethnicity. Most parents spoke English as their primary language (40 [91%]).
Among the 16 clinicians, 10 were physicians and six were nurse practitioners or physician associates. Eleven of the 16 were women and the group had a median age of 42 years. Fourteen clinicians (88%) self-identified as White individuals and two (13%) had unknown race and ethnicity.
All were interviewed on their management of pediatric diarrhea and about their expectations for diagnostic testing and treatment of the condition, as well as the perceived utility of a clinical decision support tool.
Jones and colleagues identified three motivations among parents who sought clinical care for a child with diarrhea. The first was reassurance, which the authors said included validation for what the parents were already doing to care for their child.
The second motivation was to obtain insight into the etiology of their child’s symptoms. “Many believed that diagnostic testing to identify the specific etiology of the illness would be useful. Parents indicated that knowing the etiology would offer desired reassurance and potentially inform treatment decisions,” Jones and her coauthors wrote.
Lastly, parents sought appropriate treatment and symptom relief.
Many clinicians acknowledged the benefits of a clinical decision support tool for help with evidence-based decision-making during diagnosis and to facilitate communication with families. However, they expressed skepticism over the use of diagnostics for etiology, noting that disease management was not dependent upon knowing it.
Some clinicians said many families expected a test. “Even if I don’t think that a GI [gastrointestinal] stool study is necessary, there are situations where…a family is not going to leave the [ED] happy without one. And so I probably order them sometimes when they’re not truly indicated,” a physician reported in the interview.
“That said,” Jones and her coauthors wrote, “clinicians thought that diagnostic testing for pediatric diarrhea was generally not warranted, except in unique cases [such as] bloody stools, prolonged duration of diarrhea, or travel history.”
Many clinicians thought a decision-making tool might help build trust and rapport with the patient’s family, reassuring them their child is getting evidence-based care.
“It just adds to that shared decision-making model. I think it adds trust…I think it does kind of back up our ability to defend why we’re doing what we’re doing,” reported one surveyed ED physician.
Parents were mostly wary of the potential use of a clinical decision-making tool. Jones and colleagues reported that in addition to some clinicians, “several parents expressed concerns that a tool does not account for nuances and would lead to ‘generalizing every kid’ (said the father of a child aged 1-3 years), as opposed to providing patient-centered care.”
Parents also said they worried a clinician would not reply upon their own clinical judgement if they had a diagnostic tool.
Jones and her colleagues concluded that before implementing a clinical decision support tool in pediatric diarrhea, strategies are necessary to, “resolve tension in care expectations, facilitate diagnostic stewardship, and optimize care.”
In an accompanying editorial, KC Coffey, MD, MPH, concluded that the study by Jones and colleagues suggests that adapting such tools to incorporate parental expectations, “could facilitate patient engagement in the diagnostic process and increase acceptance of [using these tools for] decisions. Such discussions might also raise awareness of the potential harms of over testing.” Coffey is an epidemiologist and infectious disease physician at the University of Maryland in Baltimore.
Elizabeth Dobler, MD, who was not involved in the study, told GI & Hepatology News that “as the number of available tests continues to grow, stewardship is becoming more relevant than ever. Families may not always realize the downsides of unnecessary testing — such as false positives, avoidable procedures, or added risks — and part of our responsibility is to help them understand both the potential benefits and the potential harms of these tests.”
Dobler is the medical director for clinical decision support in the Department of Clinical Informatics at Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago.
Clinical decision support tools are helpful in the clinical setting, Dobler said because “they give providers quick access to the most relevant information needed for decision-making. This includes patient-specific details — symptoms, history, labs, and vitals” as well as the characteristics and downsides of the tests. In an ideal world, she said, clinicians would consider these data for every patient.
Dobler cautioned however, that, “it’s important to stress that these tools don’t replace clinical judgment — the provider still evaluates the patient, considers the clinical context, and incorporates the family’s preferences. But as a complement to that process, I believe these tools are very valuable.”
Lastly, Dobler said that transparency is key to helping parents overcome their hesitancy regarding these tools.
Jones, Coffey, and Dobler reported no relevant financial disclosures.
A version of this article appeared on Medscape.com.
“Clinical decision support tools are designed to assist clinicians in making informed and accurate diagnostic and prognostic decisions using available characteristics of the patient and the larger context,” Anna Jones, MD, MPH, and her colleagues wrote in JAMA Network Open.
Jones is in the Department of Pediatrics at the University of Utah School of Medicine in Salt Lake City.
Jones and her coauthors concluded such a tool had the potential to improve evidence-based testing in pediatric diarrhea and help clinicians communicate clearly to parents the etiology of their child’s illness. Parents in the study, however, expressed skepticism over the tool, voicing concerns that physicians might over-rely on its algorithms.
The authors said that thanks to the development of multiplex polymerase chain reaction (PCR) panels for gastroenteritis, it is now possible to quickly identify up to 22 different pathogens from stool samples. What is lacking, they suggested, are protocols for knowing when to test for these pathogens.
“Although the Infectious Diseases Society of America 2017 clinical practice guidelines for the diagnosis and management of infectious diarrhea provide broad recommendations for when diarrhea-related diagnostics should be used, clear guidelines specific to the use of multiplex PCR panels do not exist,” Jones and her coauthors wrote, adding that misusing the diagnostics, however, “can lead to inappropriate antibiotic use and excess financial burdens.”
Meanwhile, communication breakdowns in the patient-doctor relationship are a leading contributor to diagnostic errors, according to the Agency for Healthcare Research and Quality. Subsequently, the National Academy of Medicine has recommended that healthcare professionals seek to engage patients and their families in the diagnostic process.
With these factors in mind, Jones and her colleagues recruited parents who had sought care for their child’s diarrhea and clinicians who routinely treat children with diarrhea. The recruits came from five urgent care sites and one emergency department (ED), all in Utah. Participants were interviewed between June 15, 2023, and January 24, 2025.
In all, the authors interviewed 44 parents (40 women; median age, 34 years). One parent (2%) identified as Asian, two (5%) as Black or African American, 15 (34%) as Hispanic or Latin, and 22 (50%) as White individuals. The remaining four participants (9%) were of unknown race and ethnicity. Most parents spoke English as their primary language (40 [91%]).
Among the 16 clinicians, 10 were physicians and six were nurse practitioners or physician associates. Eleven of the 16 were women and the group had a median age of 42 years. Fourteen clinicians (88%) self-identified as White individuals and two (13%) had unknown race and ethnicity.
All were interviewed on their management of pediatric diarrhea and about their expectations for diagnostic testing and treatment of the condition, as well as the perceived utility of a clinical decision support tool.
Jones and colleagues identified three motivations among parents who sought clinical care for a child with diarrhea. The first was reassurance, which the authors said included validation for what the parents were already doing to care for their child.
The second motivation was to obtain insight into the etiology of their child’s symptoms. “Many believed that diagnostic testing to identify the specific etiology of the illness would be useful. Parents indicated that knowing the etiology would offer desired reassurance and potentially inform treatment decisions,” Jones and her coauthors wrote.
Lastly, parents sought appropriate treatment and symptom relief.
Many clinicians acknowledged the benefits of a clinical decision support tool for help with evidence-based decision-making during diagnosis and to facilitate communication with families. However, they expressed skepticism over the use of diagnostics for etiology, noting that disease management was not dependent upon knowing it.
Some clinicians said many families expected a test. “Even if I don’t think that a GI [gastrointestinal] stool study is necessary, there are situations where…a family is not going to leave the [ED] happy without one. And so I probably order them sometimes when they’re not truly indicated,” a physician reported in the interview.
“That said,” Jones and her coauthors wrote, “clinicians thought that diagnostic testing for pediatric diarrhea was generally not warranted, except in unique cases [such as] bloody stools, prolonged duration of diarrhea, or travel history.”
Many clinicians thought a decision-making tool might help build trust and rapport with the patient’s family, reassuring them their child is getting evidence-based care.
“It just adds to that shared decision-making model. I think it adds trust…I think it does kind of back up our ability to defend why we’re doing what we’re doing,” reported one surveyed ED physician.
Parents were mostly wary of the potential use of a clinical decision-making tool. Jones and colleagues reported that in addition to some clinicians, “several parents expressed concerns that a tool does not account for nuances and would lead to ‘generalizing every kid’ (said the father of a child aged 1-3 years), as opposed to providing patient-centered care.”
Parents also said they worried a clinician would not reply upon their own clinical judgement if they had a diagnostic tool.
Jones and her colleagues concluded that before implementing a clinical decision support tool in pediatric diarrhea, strategies are necessary to, “resolve tension in care expectations, facilitate diagnostic stewardship, and optimize care.”
In an accompanying editorial, KC Coffey, MD, MPH, concluded that the study by Jones and colleagues suggests that adapting such tools to incorporate parental expectations, “could facilitate patient engagement in the diagnostic process and increase acceptance of [using these tools for] decisions. Such discussions might also raise awareness of the potential harms of over testing.” Coffey is an epidemiologist and infectious disease physician at the University of Maryland in Baltimore.
Elizabeth Dobler, MD, who was not involved in the study, told GI & Hepatology News that “as the number of available tests continues to grow, stewardship is becoming more relevant than ever. Families may not always realize the downsides of unnecessary testing — such as false positives, avoidable procedures, or added risks — and part of our responsibility is to help them understand both the potential benefits and the potential harms of these tests.”
Dobler is the medical director for clinical decision support in the Department of Clinical Informatics at Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago.
Clinical decision support tools are helpful in the clinical setting, Dobler said because “they give providers quick access to the most relevant information needed for decision-making. This includes patient-specific details — symptoms, history, labs, and vitals” as well as the characteristics and downsides of the tests. In an ideal world, she said, clinicians would consider these data for every patient.
Dobler cautioned however, that, “it’s important to stress that these tools don’t replace clinical judgment — the provider still evaluates the patient, considers the clinical context, and incorporates the family’s preferences. But as a complement to that process, I believe these tools are very valuable.”
Lastly, Dobler said that transparency is key to helping parents overcome their hesitancy regarding these tools.
Jones, Coffey, and Dobler reported no relevant financial disclosures.
A version of this article appeared on Medscape.com.
“Clinical decision support tools are designed to assist clinicians in making informed and accurate diagnostic and prognostic decisions using available characteristics of the patient and the larger context,” Anna Jones, MD, MPH, and her colleagues wrote in JAMA Network Open.
Jones is in the Department of Pediatrics at the University of Utah School of Medicine in Salt Lake City.
Jones and her coauthors concluded such a tool had the potential to improve evidence-based testing in pediatric diarrhea and help clinicians communicate clearly to parents the etiology of their child’s illness. Parents in the study, however, expressed skepticism over the tool, voicing concerns that physicians might over-rely on its algorithms.
The authors said that thanks to the development of multiplex polymerase chain reaction (PCR) panels for gastroenteritis, it is now possible to quickly identify up to 22 different pathogens from stool samples. What is lacking, they suggested, are protocols for knowing when to test for these pathogens.
“Although the Infectious Diseases Society of America 2017 clinical practice guidelines for the diagnosis and management of infectious diarrhea provide broad recommendations for when diarrhea-related diagnostics should be used, clear guidelines specific to the use of multiplex PCR panels do not exist,” Jones and her coauthors wrote, adding that misusing the diagnostics, however, “can lead to inappropriate antibiotic use and excess financial burdens.”
Meanwhile, communication breakdowns in the patient-doctor relationship are a leading contributor to diagnostic errors, according to the Agency for Healthcare Research and Quality. Subsequently, the National Academy of Medicine has recommended that healthcare professionals seek to engage patients and their families in the diagnostic process.
With these factors in mind, Jones and her colleagues recruited parents who had sought care for their child’s diarrhea and clinicians who routinely treat children with diarrhea. The recruits came from five urgent care sites and one emergency department (ED), all in Utah. Participants were interviewed between June 15, 2023, and January 24, 2025.
In all, the authors interviewed 44 parents (40 women; median age, 34 years). One parent (2%) identified as Asian, two (5%) as Black or African American, 15 (34%) as Hispanic or Latin, and 22 (50%) as White individuals. The remaining four participants (9%) were of unknown race and ethnicity. Most parents spoke English as their primary language (40 [91%]).
Among the 16 clinicians, 10 were physicians and six were nurse practitioners or physician associates. Eleven of the 16 were women and the group had a median age of 42 years. Fourteen clinicians (88%) self-identified as White individuals and two (13%) had unknown race and ethnicity.
All were interviewed on their management of pediatric diarrhea and about their expectations for diagnostic testing and treatment of the condition, as well as the perceived utility of a clinical decision support tool.
Jones and colleagues identified three motivations among parents who sought clinical care for a child with diarrhea. The first was reassurance, which the authors said included validation for what the parents were already doing to care for their child.
The second motivation was to obtain insight into the etiology of their child’s symptoms. “Many believed that diagnostic testing to identify the specific etiology of the illness would be useful. Parents indicated that knowing the etiology would offer desired reassurance and potentially inform treatment decisions,” Jones and her coauthors wrote.
Lastly, parents sought appropriate treatment and symptom relief.
Many clinicians acknowledged the benefits of a clinical decision support tool for help with evidence-based decision-making during diagnosis and to facilitate communication with families. However, they expressed skepticism over the use of diagnostics for etiology, noting that disease management was not dependent upon knowing it.
Some clinicians said many families expected a test. “Even if I don’t think that a GI [gastrointestinal] stool study is necessary, there are situations where…a family is not going to leave the [ED] happy without one. And so I probably order them sometimes when they’re not truly indicated,” a physician reported in the interview.
“That said,” Jones and her coauthors wrote, “clinicians thought that diagnostic testing for pediatric diarrhea was generally not warranted, except in unique cases [such as] bloody stools, prolonged duration of diarrhea, or travel history.”
Many clinicians thought a decision-making tool might help build trust and rapport with the patient’s family, reassuring them their child is getting evidence-based care.
“It just adds to that shared decision-making model. I think it adds trust…I think it does kind of back up our ability to defend why we’re doing what we’re doing,” reported one surveyed ED physician.
Parents were mostly wary of the potential use of a clinical decision-making tool. Jones and colleagues reported that in addition to some clinicians, “several parents expressed concerns that a tool does not account for nuances and would lead to ‘generalizing every kid’ (said the father of a child aged 1-3 years), as opposed to providing patient-centered care.”
Parents also said they worried a clinician would not reply upon their own clinical judgement if they had a diagnostic tool.
Jones and her colleagues concluded that before implementing a clinical decision support tool in pediatric diarrhea, strategies are necessary to, “resolve tension in care expectations, facilitate diagnostic stewardship, and optimize care.”
In an accompanying editorial, KC Coffey, MD, MPH, concluded that the study by Jones and colleagues suggests that adapting such tools to incorporate parental expectations, “could facilitate patient engagement in the diagnostic process and increase acceptance of [using these tools for] decisions. Such discussions might also raise awareness of the potential harms of over testing.” Coffey is an epidemiologist and infectious disease physician at the University of Maryland in Baltimore.
Elizabeth Dobler, MD, who was not involved in the study, told GI & Hepatology News that “as the number of available tests continues to grow, stewardship is becoming more relevant than ever. Families may not always realize the downsides of unnecessary testing — such as false positives, avoidable procedures, or added risks — and part of our responsibility is to help them understand both the potential benefits and the potential harms of these tests.”
Dobler is the medical director for clinical decision support in the Department of Clinical Informatics at Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago.
Clinical decision support tools are helpful in the clinical setting, Dobler said because “they give providers quick access to the most relevant information needed for decision-making. This includes patient-specific details — symptoms, history, labs, and vitals” as well as the characteristics and downsides of the tests. In an ideal world, she said, clinicians would consider these data for every patient.
Dobler cautioned however, that, “it’s important to stress that these tools don’t replace clinical judgment — the provider still evaluates the patient, considers the clinical context, and incorporates the family’s preferences. But as a complement to that process, I believe these tools are very valuable.”
Lastly, Dobler said that transparency is key to helping parents overcome their hesitancy regarding these tools.
Jones, Coffey, and Dobler reported no relevant financial disclosures.
A version of this article appeared on Medscape.com.
Are Probiotics for Pouchitis Prevention Worth the Cost?
, but its cost-effectiveness depends on relapse risk and may only be justified in patients who experience frequent relapses of pouchitis, a new analysis showed.
“Our findings highlight that while probiotic treatments can reduce the risk of this complication, their high costs limit their overall value for most patients,” lead author Gaurav Syal, MD, a gastroenterologist at UCLA Health, said in a statement.
“Our analysis can help guide shared decision-making between patients, clinicians, and payers to ensure resources are used where they can provide the most benefit,” Syal added.
The study was published online in Gastro Hep Advances.
Common Complication After Ulcerative Colitis Surgery
Pouchitis is a common complication in patients with ulcerative colitis who undergo restorative proctocolectomy with IPAA, with a cumulative incidence of around 48% at 2 years and 80% at 30 years.
Many patients who experience pouchitis have a single episode and respond well to short antibiotic courses. However, others develop recurrent or relapsing pouchitis, and 17% progress to a chronic form that can become dependent on antibiotics or refractory to antibiotics.
An eight-strain probiotic was shown to be effective in primary and secondary prevention of pouchitis in randomized, placebo-controlled trials.
Syal and colleagues sought to determine whether it’s worth the cost.
They constructed decision-tree models with Markov simulations to compare the risk for initial development and recurrence of pouchitis over a 2-year period between no prophylaxis and daily use of the eight-strain probiotic.
In the primary prophylaxis model, the cycle length was 2 weeks and pouchitis treatment sequence was ciprofloxacin, metronidazole and ciprofloxacin-tinidazole. In the secondary prophylaxis model, the cycle length was 4 weeks and pouchitis treatment sequence was initially the same as the primary prophylaxis model with the addition of vedolizumab and infliximab.
Costs were calculated from a US third-party payer perspective, using a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY).
For primary prevention, the probiotic slightly increased QALYs compared with no probiotic (0.927 vs 0.918) but at a far higher cost ($2223 vs $299), resulting in an incremental cost-effectiveness ratio (ICER) of $236,076 per QALY — well above the accepted threshold.
In patients with infrequent relapses, probiotic use was slightly more effective than no use of probiotic (cumulative QALYs, 1.26 vs 1.24) but more expensive ($3370 vs $557), yielding an ICER of $153,011 per QALY — again above the accepted threshold.
However, sensitivity analyses revealed that the probiotic was cost-effective in patients with frequent relapsing pouchitis — defined as two or more episodes per year.
In this subgroup, the ICER dropped below the willingness-to-pay threshold of $100,000 per QALY, and in some scenarios, the probiotic even became the dominant strategy, meaning it was both more effective and less costly than no prophylaxis, the researchers noted.
Current guidelines from AGA on managing pouchitis suggest using probiotics to prevent recurrent episodes of pouchitis with a caveat that those who experience infrequent episodes may choose to avoid secondary prevention strategies.
“Our findings supplement the guidelines by confirming that the eight-strain probiotics can be cost-effective in frequent relapsing not in infrequent relapsing pouchitis,” the authors wrote.
They also noted that the probiotic cost itself was the biggest driver of results, accounting for 95% of the total cost in the primary prevention model. According to their analysis, reducing its price by half could make it a cost-effective option more broadly.
They also noted that probiotic prophylaxis could be cost-effective for patients at higher-than-average risk, such as those with primary sclerosing cholangitis (PSC), who have 4.2 times higher odds of developing pouchitis than peers without PSC.
But they cautioned that “further research is warranted on the effectiveness of the eight-strain probiotic for primary prevention of pouchitis in patients with ulcerative colitis and IPAA and PSC.”
The study had no financial support. Syal reported receiving research support from Pfizer.
A version of this article appeared on Medscape.com.
, but its cost-effectiveness depends on relapse risk and may only be justified in patients who experience frequent relapses of pouchitis, a new analysis showed.
“Our findings highlight that while probiotic treatments can reduce the risk of this complication, their high costs limit their overall value for most patients,” lead author Gaurav Syal, MD, a gastroenterologist at UCLA Health, said in a statement.
“Our analysis can help guide shared decision-making between patients, clinicians, and payers to ensure resources are used where they can provide the most benefit,” Syal added.
The study was published online in Gastro Hep Advances.
Common Complication After Ulcerative Colitis Surgery
Pouchitis is a common complication in patients with ulcerative colitis who undergo restorative proctocolectomy with IPAA, with a cumulative incidence of around 48% at 2 years and 80% at 30 years.
Many patients who experience pouchitis have a single episode and respond well to short antibiotic courses. However, others develop recurrent or relapsing pouchitis, and 17% progress to a chronic form that can become dependent on antibiotics or refractory to antibiotics.
An eight-strain probiotic was shown to be effective in primary and secondary prevention of pouchitis in randomized, placebo-controlled trials.
Syal and colleagues sought to determine whether it’s worth the cost.
They constructed decision-tree models with Markov simulations to compare the risk for initial development and recurrence of pouchitis over a 2-year period between no prophylaxis and daily use of the eight-strain probiotic.
In the primary prophylaxis model, the cycle length was 2 weeks and pouchitis treatment sequence was ciprofloxacin, metronidazole and ciprofloxacin-tinidazole. In the secondary prophylaxis model, the cycle length was 4 weeks and pouchitis treatment sequence was initially the same as the primary prophylaxis model with the addition of vedolizumab and infliximab.
Costs were calculated from a US third-party payer perspective, using a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY).
For primary prevention, the probiotic slightly increased QALYs compared with no probiotic (0.927 vs 0.918) but at a far higher cost ($2223 vs $299), resulting in an incremental cost-effectiveness ratio (ICER) of $236,076 per QALY — well above the accepted threshold.
In patients with infrequent relapses, probiotic use was slightly more effective than no use of probiotic (cumulative QALYs, 1.26 vs 1.24) but more expensive ($3370 vs $557), yielding an ICER of $153,011 per QALY — again above the accepted threshold.
However, sensitivity analyses revealed that the probiotic was cost-effective in patients with frequent relapsing pouchitis — defined as two or more episodes per year.
In this subgroup, the ICER dropped below the willingness-to-pay threshold of $100,000 per QALY, and in some scenarios, the probiotic even became the dominant strategy, meaning it was both more effective and less costly than no prophylaxis, the researchers noted.
Current guidelines from AGA on managing pouchitis suggest using probiotics to prevent recurrent episodes of pouchitis with a caveat that those who experience infrequent episodes may choose to avoid secondary prevention strategies.
“Our findings supplement the guidelines by confirming that the eight-strain probiotics can be cost-effective in frequent relapsing not in infrequent relapsing pouchitis,” the authors wrote.
They also noted that the probiotic cost itself was the biggest driver of results, accounting for 95% of the total cost in the primary prevention model. According to their analysis, reducing its price by half could make it a cost-effective option more broadly.
They also noted that probiotic prophylaxis could be cost-effective for patients at higher-than-average risk, such as those with primary sclerosing cholangitis (PSC), who have 4.2 times higher odds of developing pouchitis than peers without PSC.
But they cautioned that “further research is warranted on the effectiveness of the eight-strain probiotic for primary prevention of pouchitis in patients with ulcerative colitis and IPAA and PSC.”
The study had no financial support. Syal reported receiving research support from Pfizer.
A version of this article appeared on Medscape.com.
, but its cost-effectiveness depends on relapse risk and may only be justified in patients who experience frequent relapses of pouchitis, a new analysis showed.
“Our findings highlight that while probiotic treatments can reduce the risk of this complication, their high costs limit their overall value for most patients,” lead author Gaurav Syal, MD, a gastroenterologist at UCLA Health, said in a statement.
“Our analysis can help guide shared decision-making between patients, clinicians, and payers to ensure resources are used where they can provide the most benefit,” Syal added.
The study was published online in Gastro Hep Advances.
Common Complication After Ulcerative Colitis Surgery
Pouchitis is a common complication in patients with ulcerative colitis who undergo restorative proctocolectomy with IPAA, with a cumulative incidence of around 48% at 2 years and 80% at 30 years.
Many patients who experience pouchitis have a single episode and respond well to short antibiotic courses. However, others develop recurrent or relapsing pouchitis, and 17% progress to a chronic form that can become dependent on antibiotics or refractory to antibiotics.
An eight-strain probiotic was shown to be effective in primary and secondary prevention of pouchitis in randomized, placebo-controlled trials.
Syal and colleagues sought to determine whether it’s worth the cost.
They constructed decision-tree models with Markov simulations to compare the risk for initial development and recurrence of pouchitis over a 2-year period between no prophylaxis and daily use of the eight-strain probiotic.
In the primary prophylaxis model, the cycle length was 2 weeks and pouchitis treatment sequence was ciprofloxacin, metronidazole and ciprofloxacin-tinidazole. In the secondary prophylaxis model, the cycle length was 4 weeks and pouchitis treatment sequence was initially the same as the primary prophylaxis model with the addition of vedolizumab and infliximab.
Costs were calculated from a US third-party payer perspective, using a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY).
For primary prevention, the probiotic slightly increased QALYs compared with no probiotic (0.927 vs 0.918) but at a far higher cost ($2223 vs $299), resulting in an incremental cost-effectiveness ratio (ICER) of $236,076 per QALY — well above the accepted threshold.
In patients with infrequent relapses, probiotic use was slightly more effective than no use of probiotic (cumulative QALYs, 1.26 vs 1.24) but more expensive ($3370 vs $557), yielding an ICER of $153,011 per QALY — again above the accepted threshold.
However, sensitivity analyses revealed that the probiotic was cost-effective in patients with frequent relapsing pouchitis — defined as two or more episodes per year.
In this subgroup, the ICER dropped below the willingness-to-pay threshold of $100,000 per QALY, and in some scenarios, the probiotic even became the dominant strategy, meaning it was both more effective and less costly than no prophylaxis, the researchers noted.
Current guidelines from AGA on managing pouchitis suggest using probiotics to prevent recurrent episodes of pouchitis with a caveat that those who experience infrequent episodes may choose to avoid secondary prevention strategies.
“Our findings supplement the guidelines by confirming that the eight-strain probiotics can be cost-effective in frequent relapsing not in infrequent relapsing pouchitis,” the authors wrote.
They also noted that the probiotic cost itself was the biggest driver of results, accounting for 95% of the total cost in the primary prevention model. According to their analysis, reducing its price by half could make it a cost-effective option more broadly.
They also noted that probiotic prophylaxis could be cost-effective for patients at higher-than-average risk, such as those with primary sclerosing cholangitis (PSC), who have 4.2 times higher odds of developing pouchitis than peers without PSC.
But they cautioned that “further research is warranted on the effectiveness of the eight-strain probiotic for primary prevention of pouchitis in patients with ulcerative colitis and IPAA and PSC.”
The study had no financial support. Syal reported receiving research support from Pfizer.
A version of this article appeared on Medscape.com.
FROM GASTRO HEP ADVANCES
Large Language Models Cut Time, Cost of Guideline Development
, according to a pilot study from the American Gastroenterological Association (AGA).
Faster, cheaper study screening could allow societies to update clinical recommendations more frequently, improving alignment with the latest evidence, lead author Sunny Chung, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.
“Each guideline typically requires 5 to 15 systematic reviews, making the process time-consuming (averaging more than 60 weeks) and costly (more than $140,000),” the investigators wrote in Gastroenterology . “One of the most critical yet time-consuming steps in systematic reviews is title and abstract screening. LLMs have the potential to make this step more efficient.”
To test this approach, the investigators developed, validated, and applied a dual-model LLM screening pipeline with human-in-the-loop oversight, focusing on randomized controlled trials in AGA guidelines.
The system was built using the 2021 guideline on moderate-to-severe Crohn’s disease, targeting biologic therapies for induction and maintenance of remission.
Using chain-of-thought prompting and structured inclusion criteria based on the PICO framework, the investigators deployed GPT-4o (OpenAI) and Gemini-1.5-Pro (Google DeepMind) as independent screeners, each assessing titles and abstracts according to standardized logic encoded in JavaScript Object Notation. This approach mimicked a traditional double-reviewer system.
After initial testing, the pipeline was validated in a 2025 update of the same guideline, this time spanning 6 focused clinical questions on advanced therapies and immunomodulators. Results were compared against manual screening by 2 experienced human reviewers, with total screening time documented.
The system was then tested across 4 additional guideline topics: fecal microbiota transplantation (FMT) for irritable bowel syndrome and Clostridioides difficile, gastroparesis, and hepatocellular carcinoma. A final test applied the system to a forthcoming guideline on complications of acute pancreatitis.
Across all topics, the dual-LLM system achieved 100% sensitivity in identifying randomized controlled trials (RCTs). For the 2025 update of the AGA guideline on Crohn’s disease, the models flagged 418 of 4,377 abstracts for inclusion, captur-ing all 25 relevant RCTs in just 48 minutes. Manual screening of the same dataset previously took almost 13 hours.
Comparable accuracy and time savings were observed for the other topics.
The pipeline correctly flagged all 13 RCTs in 4,820 studies on FMT for irritable bowel syndrome, and all 16 RCTs in 5,587 studies on FMT for Clostridioides difficile, requiring 27 and 66 minutes, respectively. Similarly, the system captured all 11 RCTs in 3,919 hepatocellular carcinoma abstracts and all 18 RCTs in 1,578 studies on gastroparesis, completing each task in under 65 minutes. Early testing on the upcoming guideline for pancreatitis yielded similar results.
Cost analysis underscored the efficiency of this approach. At an estimated $175–200 per hour for expert screeners, traditional abstract screening would cost around $2,500 per review, versus approximately $100 for the LLM approach—a 96% reduction.
The investigators cautioned that human oversight remains necessary to verify the relevance of studies flagged by the models. While the system’s sensitivity was consistent, it also selected articles that were ultimately excluded by expert reviewers. Broader validation will be required to assess performance across non-RCT study designs, such as observational or case-control studies, they added.
“As medical literature continues to expand, the integration of artificial intelligence into evidence synthesis processes will become increasingly vital,” Dr. Chung and colleagues wrote. “With further refinement and broader validation, this LLM-based pipeline has the potential to revolutionize evidence synthesis and set a new standard for guideline development.”
This study was funded by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest.
Ethan Goh, MD, executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, described the AGA pilot as both timely and promising.
“I’m certainly bullish about the use case,” he said in an interview. “Their study design and application is also robust, so I would congratulate them.”
Goh, a general editor for BMJ Digital Health & AI, predicted “huge potential” in the strategy for both clinicians and the general population, who benefit from the most up-to-date guidelines possible.
“I believe that using AI can represent a much faster, more cost effective, efficient way of gathering all these information sources,” he said.
Still, humans will need to be involved in the process.
“[This AI-driven approach] will always need some degree of expert oversight and judgement,” Goh said.
Speaking more broadly about automating study aggregation, Goh said AI may still struggle to determine which studies are most clinically relevant.
“When we use [AI models] to pull out medical references, anecdotally, I don’t think they’re always getting the best ones all the time, or even necessarily the right ones,” he said.
And as AI models grow more impressive, these shortcomings become less apparent, potentially lulling humans into overconfidence.
“Humans are humans,” Goh said. “We get lazy over time. That will be one of the challenges. As the systems get increasingly good, humans start to defer more and more of their judgment to them and say, ‘All right, AI, you’re doing good. Just do 100% automation.’ And then [people] start fact checking or reviewing even less.”
AI could also undermine automated reviews in another way: AI-generated publications that appear genuine, but aren’t, may creep into the dataset.
Despite these concerns, Goh concluded on an optimistic note.
“I think that there are huge ways to use AI, tools, not to replace, but to augment and support human judgment,” he said.
Ethan Goh, MD, is senior research engineer and executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, at Stanford (Calif.) University. He declared no conflicts of interest.
Ethan Goh, MD, executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, described the AGA pilot as both timely and promising.
“I’m certainly bullish about the use case,” he said in an interview. “Their study design and application is also robust, so I would congratulate them.”
Goh, a general editor for BMJ Digital Health & AI, predicted “huge potential” in the strategy for both clinicians and the general population, who benefit from the most up-to-date guidelines possible.
“I believe that using AI can represent a much faster, more cost effective, efficient way of gathering all these information sources,” he said.
Still, humans will need to be involved in the process.
“[This AI-driven approach] will always need some degree of expert oversight and judgement,” Goh said.
Speaking more broadly about automating study aggregation, Goh said AI may still struggle to determine which studies are most clinically relevant.
“When we use [AI models] to pull out medical references, anecdotally, I don’t think they’re always getting the best ones all the time, or even necessarily the right ones,” he said.
And as AI models grow more impressive, these shortcomings become less apparent, potentially lulling humans into overconfidence.
“Humans are humans,” Goh said. “We get lazy over time. That will be one of the challenges. As the systems get increasingly good, humans start to defer more and more of their judgment to them and say, ‘All right, AI, you’re doing good. Just do 100% automation.’ And then [people] start fact checking or reviewing even less.”
AI could also undermine automated reviews in another way: AI-generated publications that appear genuine, but aren’t, may creep into the dataset.
Despite these concerns, Goh concluded on an optimistic note.
“I think that there are huge ways to use AI, tools, not to replace, but to augment and support human judgment,” he said.
Ethan Goh, MD, is senior research engineer and executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, at Stanford (Calif.) University. He declared no conflicts of interest.
Ethan Goh, MD, executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, described the AGA pilot as both timely and promising.
“I’m certainly bullish about the use case,” he said in an interview. “Their study design and application is also robust, so I would congratulate them.”
Goh, a general editor for BMJ Digital Health & AI, predicted “huge potential” in the strategy for both clinicians and the general population, who benefit from the most up-to-date guidelines possible.
“I believe that using AI can represent a much faster, more cost effective, efficient way of gathering all these information sources,” he said.
Still, humans will need to be involved in the process.
“[This AI-driven approach] will always need some degree of expert oversight and judgement,” Goh said.
Speaking more broadly about automating study aggregation, Goh said AI may still struggle to determine which studies are most clinically relevant.
“When we use [AI models] to pull out medical references, anecdotally, I don’t think they’re always getting the best ones all the time, or even necessarily the right ones,” he said.
And as AI models grow more impressive, these shortcomings become less apparent, potentially lulling humans into overconfidence.
“Humans are humans,” Goh said. “We get lazy over time. That will be one of the challenges. As the systems get increasingly good, humans start to defer more and more of their judgment to them and say, ‘All right, AI, you’re doing good. Just do 100% automation.’ And then [people] start fact checking or reviewing even less.”
AI could also undermine automated reviews in another way: AI-generated publications that appear genuine, but aren’t, may creep into the dataset.
Despite these concerns, Goh concluded on an optimistic note.
“I think that there are huge ways to use AI, tools, not to replace, but to augment and support human judgment,” he said.
Ethan Goh, MD, is senior research engineer and executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, at Stanford (Calif.) University. He declared no conflicts of interest.
, according to a pilot study from the American Gastroenterological Association (AGA).
Faster, cheaper study screening could allow societies to update clinical recommendations more frequently, improving alignment with the latest evidence, lead author Sunny Chung, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.
“Each guideline typically requires 5 to 15 systematic reviews, making the process time-consuming (averaging more than 60 weeks) and costly (more than $140,000),” the investigators wrote in Gastroenterology . “One of the most critical yet time-consuming steps in systematic reviews is title and abstract screening. LLMs have the potential to make this step more efficient.”
To test this approach, the investigators developed, validated, and applied a dual-model LLM screening pipeline with human-in-the-loop oversight, focusing on randomized controlled trials in AGA guidelines.
The system was built using the 2021 guideline on moderate-to-severe Crohn’s disease, targeting biologic therapies for induction and maintenance of remission.
Using chain-of-thought prompting and structured inclusion criteria based on the PICO framework, the investigators deployed GPT-4o (OpenAI) and Gemini-1.5-Pro (Google DeepMind) as independent screeners, each assessing titles and abstracts according to standardized logic encoded in JavaScript Object Notation. This approach mimicked a traditional double-reviewer system.
After initial testing, the pipeline was validated in a 2025 update of the same guideline, this time spanning 6 focused clinical questions on advanced therapies and immunomodulators. Results were compared against manual screening by 2 experienced human reviewers, with total screening time documented.
The system was then tested across 4 additional guideline topics: fecal microbiota transplantation (FMT) for irritable bowel syndrome and Clostridioides difficile, gastroparesis, and hepatocellular carcinoma. A final test applied the system to a forthcoming guideline on complications of acute pancreatitis.
Across all topics, the dual-LLM system achieved 100% sensitivity in identifying randomized controlled trials (RCTs). For the 2025 update of the AGA guideline on Crohn’s disease, the models flagged 418 of 4,377 abstracts for inclusion, captur-ing all 25 relevant RCTs in just 48 minutes. Manual screening of the same dataset previously took almost 13 hours.
Comparable accuracy and time savings were observed for the other topics.
The pipeline correctly flagged all 13 RCTs in 4,820 studies on FMT for irritable bowel syndrome, and all 16 RCTs in 5,587 studies on FMT for Clostridioides difficile, requiring 27 and 66 minutes, respectively. Similarly, the system captured all 11 RCTs in 3,919 hepatocellular carcinoma abstracts and all 18 RCTs in 1,578 studies on gastroparesis, completing each task in under 65 minutes. Early testing on the upcoming guideline for pancreatitis yielded similar results.
Cost analysis underscored the efficiency of this approach. At an estimated $175–200 per hour for expert screeners, traditional abstract screening would cost around $2,500 per review, versus approximately $100 for the LLM approach—a 96% reduction.
The investigators cautioned that human oversight remains necessary to verify the relevance of studies flagged by the models. While the system’s sensitivity was consistent, it also selected articles that were ultimately excluded by expert reviewers. Broader validation will be required to assess performance across non-RCT study designs, such as observational or case-control studies, they added.
“As medical literature continues to expand, the integration of artificial intelligence into evidence synthesis processes will become increasingly vital,” Dr. Chung and colleagues wrote. “With further refinement and broader validation, this LLM-based pipeline has the potential to revolutionize evidence synthesis and set a new standard for guideline development.”
This study was funded by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest.
, according to a pilot study from the American Gastroenterological Association (AGA).
Faster, cheaper study screening could allow societies to update clinical recommendations more frequently, improving alignment with the latest evidence, lead author Sunny Chung, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.
“Each guideline typically requires 5 to 15 systematic reviews, making the process time-consuming (averaging more than 60 weeks) and costly (more than $140,000),” the investigators wrote in Gastroenterology . “One of the most critical yet time-consuming steps in systematic reviews is title and abstract screening. LLMs have the potential to make this step more efficient.”
To test this approach, the investigators developed, validated, and applied a dual-model LLM screening pipeline with human-in-the-loop oversight, focusing on randomized controlled trials in AGA guidelines.
The system was built using the 2021 guideline on moderate-to-severe Crohn’s disease, targeting biologic therapies for induction and maintenance of remission.
Using chain-of-thought prompting and structured inclusion criteria based on the PICO framework, the investigators deployed GPT-4o (OpenAI) and Gemini-1.5-Pro (Google DeepMind) as independent screeners, each assessing titles and abstracts according to standardized logic encoded in JavaScript Object Notation. This approach mimicked a traditional double-reviewer system.
After initial testing, the pipeline was validated in a 2025 update of the same guideline, this time spanning 6 focused clinical questions on advanced therapies and immunomodulators. Results were compared against manual screening by 2 experienced human reviewers, with total screening time documented.
The system was then tested across 4 additional guideline topics: fecal microbiota transplantation (FMT) for irritable bowel syndrome and Clostridioides difficile, gastroparesis, and hepatocellular carcinoma. A final test applied the system to a forthcoming guideline on complications of acute pancreatitis.
Across all topics, the dual-LLM system achieved 100% sensitivity in identifying randomized controlled trials (RCTs). For the 2025 update of the AGA guideline on Crohn’s disease, the models flagged 418 of 4,377 abstracts for inclusion, captur-ing all 25 relevant RCTs in just 48 minutes. Manual screening of the same dataset previously took almost 13 hours.
Comparable accuracy and time savings were observed for the other topics.
The pipeline correctly flagged all 13 RCTs in 4,820 studies on FMT for irritable bowel syndrome, and all 16 RCTs in 5,587 studies on FMT for Clostridioides difficile, requiring 27 and 66 minutes, respectively. Similarly, the system captured all 11 RCTs in 3,919 hepatocellular carcinoma abstracts and all 18 RCTs in 1,578 studies on gastroparesis, completing each task in under 65 minutes. Early testing on the upcoming guideline for pancreatitis yielded similar results.
Cost analysis underscored the efficiency of this approach. At an estimated $175–200 per hour for expert screeners, traditional abstract screening would cost around $2,500 per review, versus approximately $100 for the LLM approach—a 96% reduction.
The investigators cautioned that human oversight remains necessary to verify the relevance of studies flagged by the models. While the system’s sensitivity was consistent, it also selected articles that were ultimately excluded by expert reviewers. Broader validation will be required to assess performance across non-RCT study designs, such as observational or case-control studies, they added.
“As medical literature continues to expand, the integration of artificial intelligence into evidence synthesis processes will become increasingly vital,” Dr. Chung and colleagues wrote. “With further refinement and broader validation, this LLM-based pipeline has the potential to revolutionize evidence synthesis and set a new standard for guideline development.”
This study was funded by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest.
FROM GASTROENTEROLOGY
New Guidelines for Pregnancy and IBD Aim to Quell Fears
, suggesting this approach will not harm the fetus.
The guidelines also recommend that all women with IBD receive preconception counseling and be followed as high-risk pregnancies.
“Management of chronic illness in pregnant women has always been defined by fear of harming the fetus,” said Uma Mahadevan, MD, AGAF, director of the Colitis and Crohn’s Disease Center at the University of California San Francisco and chair of the Global Consensus Consortium that developed the guidelines.
As a result, pregnant women are excluded from clinical trials of experimental therapies for IBD. And when a new therapy achieves regulatory approval, there are no human pregnancy safety data, only animal data. To fill this gap, the PIANO study, of which Mahadevan is principal investigator, looked at the safety of IBD medications in pregnancy and short- and long-term outcomes of the children.
“With our ongoing work in pregnancy in the patient with IBD, we realized that inflammation in the mother is the leading cause of poor outcome for the infant,” she told GI & Hepatology News.
“We also have a better understanding of placental transfer of biologic agents” and the lack of exposure to the fetus during the first trimester, “a key period of organogenesis,” she added.
Final recommendations were published simultaneously in six international journals, namely, Clinical Gastroenterology and Hepatology, American Journal of Gastroenterology, GUT, Inflammatory Bowel Diseases, Journal of Crohn’s and Colitis, and Alimentary Pharmacology and Therapeutics.
Surprising, Novel Findings
Limited provider knowledge led to varied practices in caring for women with IBD who become pregnant, according to the consensus authors. Practices are affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus.
“The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike,” the authors of the guidelines wrote.
Therefore, the Global Consensus Consortium — a group of 39 IBD experts, including teratologists and maternal fetal medicine specialists and seven patient advocates from six continents — convened to review and assess current data and come to an agreement on best practices. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used when sufficient published data were available, and the Research and Development process when expert opinion was needed to guide consistent practice.
“Some of the findings were expected, but others were novel,” said Mahadevan.
Recommendations that might surprise clinicians include GRADE statement 9, which suggests that pregnant women with IBD take low-dose aspirin by 12 to 16 weeks’ gestation to prevent preterm preeclampsia. “This is based on the ASPRE study, showing that women at risk of preeclampsia can lower their risk by taking low-dose aspirin,” with no risk for flare, Mahadevan said.
In addition, GRADE statements 17-20 recommend/suggest that women continue their biologic throughout pregnancy without stopping. “North America has always recommended continuing during the third trimester, while Europe only recently has come to this,” Mahadevan said. “However, there was always some looseness about stopping at week X, Y, or Z. Now, we do recommend continuing the dose on schedule with no holding.”
Continuing medications considered low risk for use during pregnancy, such as 5-amino salicylic acids, sulfasalazine, thiopurines, and all monoclonal antibodies during preconception, pregnancy, and lactation, was also recommended.
However, small-molecule drugs such as S1P receptor molecules and JAK inhibitors should be avoided for at least 1 month, and in some cases for 3 months prior to attempting conception, unless there is no alternative for the health of the mother. They should also be avoided during lactation.
Grade statement 33, which suggests that live rotavirus vaccine may be provided in children with in utero exposure to biologics, is also new, Mahadevan noted. “All prior recommendations were that no live vaccine should be given in the first 6 months or longer if infants were exposed to biologics in utero, but based on a prospective Canadian study, there is no harm when given to these infants.”
Another novel recommendation is that women with IBD on any monoclonal antibodies, including newer interleukin-23s, may breastfeed even though there are not clinical trial data at this point. The recommendation to continue them through pregnancy and lactation is based on placental physiology, as well as on the physiology of monoclonal antibody transfer in breast milk, according to the consortium.
Furthermore, the authors noted, there was no increase in infant infections at 4 months or 12 months if they were exposed to a biologic or thiopurine (or both) during pregnancy.
Overall, the consortium recommended that all pregnancies for women with IBD be considered as “high risk” for complications. This is due to the fact that many parts of the world, including the US, are “resource-limited,” Mahadevan explained. Since maternal fetal medicine specialists are not widely available, the consortium suggested all these patients be followed with increased monitoring and surveillance based on available resources.
In addition to the guidelines, patient videos in seven languages, a professional slide deck in English and Spanish, and a video on the global consensus are all available at https://pianostudy.org/.
This study was funded by The Leona B. and Harry H. Helmsley Charitable Trust.
Mahadevan reported being a consultant for AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Enveda, Gilead, Janssen, Lilly, Merck, Pfizer, Protagonist, Roivant, and Takeda.
A version of this article appeared on Medscape.com.
, suggesting this approach will not harm the fetus.
The guidelines also recommend that all women with IBD receive preconception counseling and be followed as high-risk pregnancies.
“Management of chronic illness in pregnant women has always been defined by fear of harming the fetus,” said Uma Mahadevan, MD, AGAF, director of the Colitis and Crohn’s Disease Center at the University of California San Francisco and chair of the Global Consensus Consortium that developed the guidelines.
As a result, pregnant women are excluded from clinical trials of experimental therapies for IBD. And when a new therapy achieves regulatory approval, there are no human pregnancy safety data, only animal data. To fill this gap, the PIANO study, of which Mahadevan is principal investigator, looked at the safety of IBD medications in pregnancy and short- and long-term outcomes of the children.
“With our ongoing work in pregnancy in the patient with IBD, we realized that inflammation in the mother is the leading cause of poor outcome for the infant,” she told GI & Hepatology News.
“We also have a better understanding of placental transfer of biologic agents” and the lack of exposure to the fetus during the first trimester, “a key period of organogenesis,” she added.
Final recommendations were published simultaneously in six international journals, namely, Clinical Gastroenterology and Hepatology, American Journal of Gastroenterology, GUT, Inflammatory Bowel Diseases, Journal of Crohn’s and Colitis, and Alimentary Pharmacology and Therapeutics.
Surprising, Novel Findings
Limited provider knowledge led to varied practices in caring for women with IBD who become pregnant, according to the consensus authors. Practices are affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus.
“The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike,” the authors of the guidelines wrote.
Therefore, the Global Consensus Consortium — a group of 39 IBD experts, including teratologists and maternal fetal medicine specialists and seven patient advocates from six continents — convened to review and assess current data and come to an agreement on best practices. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used when sufficient published data were available, and the Research and Development process when expert opinion was needed to guide consistent practice.
“Some of the findings were expected, but others were novel,” said Mahadevan.
Recommendations that might surprise clinicians include GRADE statement 9, which suggests that pregnant women with IBD take low-dose aspirin by 12 to 16 weeks’ gestation to prevent preterm preeclampsia. “This is based on the ASPRE study, showing that women at risk of preeclampsia can lower their risk by taking low-dose aspirin,” with no risk for flare, Mahadevan said.
In addition, GRADE statements 17-20 recommend/suggest that women continue their biologic throughout pregnancy without stopping. “North America has always recommended continuing during the third trimester, while Europe only recently has come to this,” Mahadevan said. “However, there was always some looseness about stopping at week X, Y, or Z. Now, we do recommend continuing the dose on schedule with no holding.”
Continuing medications considered low risk for use during pregnancy, such as 5-amino salicylic acids, sulfasalazine, thiopurines, and all monoclonal antibodies during preconception, pregnancy, and lactation, was also recommended.
However, small-molecule drugs such as S1P receptor molecules and JAK inhibitors should be avoided for at least 1 month, and in some cases for 3 months prior to attempting conception, unless there is no alternative for the health of the mother. They should also be avoided during lactation.
Grade statement 33, which suggests that live rotavirus vaccine may be provided in children with in utero exposure to biologics, is also new, Mahadevan noted. “All prior recommendations were that no live vaccine should be given in the first 6 months or longer if infants were exposed to biologics in utero, but based on a prospective Canadian study, there is no harm when given to these infants.”
Another novel recommendation is that women with IBD on any monoclonal antibodies, including newer interleukin-23s, may breastfeed even though there are not clinical trial data at this point. The recommendation to continue them through pregnancy and lactation is based on placental physiology, as well as on the physiology of monoclonal antibody transfer in breast milk, according to the consortium.
Furthermore, the authors noted, there was no increase in infant infections at 4 months or 12 months if they were exposed to a biologic or thiopurine (or both) during pregnancy.
Overall, the consortium recommended that all pregnancies for women with IBD be considered as “high risk” for complications. This is due to the fact that many parts of the world, including the US, are “resource-limited,” Mahadevan explained. Since maternal fetal medicine specialists are not widely available, the consortium suggested all these patients be followed with increased monitoring and surveillance based on available resources.
In addition to the guidelines, patient videos in seven languages, a professional slide deck in English and Spanish, and a video on the global consensus are all available at https://pianostudy.org/.
This study was funded by The Leona B. and Harry H. Helmsley Charitable Trust.
Mahadevan reported being a consultant for AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Enveda, Gilead, Janssen, Lilly, Merck, Pfizer, Protagonist, Roivant, and Takeda.
A version of this article appeared on Medscape.com.
, suggesting this approach will not harm the fetus.
The guidelines also recommend that all women with IBD receive preconception counseling and be followed as high-risk pregnancies.
“Management of chronic illness in pregnant women has always been defined by fear of harming the fetus,” said Uma Mahadevan, MD, AGAF, director of the Colitis and Crohn’s Disease Center at the University of California San Francisco and chair of the Global Consensus Consortium that developed the guidelines.
As a result, pregnant women are excluded from clinical trials of experimental therapies for IBD. And when a new therapy achieves regulatory approval, there are no human pregnancy safety data, only animal data. To fill this gap, the PIANO study, of which Mahadevan is principal investigator, looked at the safety of IBD medications in pregnancy and short- and long-term outcomes of the children.
“With our ongoing work in pregnancy in the patient with IBD, we realized that inflammation in the mother is the leading cause of poor outcome for the infant,” she told GI & Hepatology News.
“We also have a better understanding of placental transfer of biologic agents” and the lack of exposure to the fetus during the first trimester, “a key period of organogenesis,” she added.
Final recommendations were published simultaneously in six international journals, namely, Clinical Gastroenterology and Hepatology, American Journal of Gastroenterology, GUT, Inflammatory Bowel Diseases, Journal of Crohn’s and Colitis, and Alimentary Pharmacology and Therapeutics.
Surprising, Novel Findings
Limited provider knowledge led to varied practices in caring for women with IBD who become pregnant, according to the consensus authors. Practices are affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus.
“The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike,” the authors of the guidelines wrote.
Therefore, the Global Consensus Consortium — a group of 39 IBD experts, including teratologists and maternal fetal medicine specialists and seven patient advocates from six continents — convened to review and assess current data and come to an agreement on best practices. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used when sufficient published data were available, and the Research and Development process when expert opinion was needed to guide consistent practice.
“Some of the findings were expected, but others were novel,” said Mahadevan.
Recommendations that might surprise clinicians include GRADE statement 9, which suggests that pregnant women with IBD take low-dose aspirin by 12 to 16 weeks’ gestation to prevent preterm preeclampsia. “This is based on the ASPRE study, showing that women at risk of preeclampsia can lower their risk by taking low-dose aspirin,” with no risk for flare, Mahadevan said.
In addition, GRADE statements 17-20 recommend/suggest that women continue their biologic throughout pregnancy without stopping. “North America has always recommended continuing during the third trimester, while Europe only recently has come to this,” Mahadevan said. “However, there was always some looseness about stopping at week X, Y, or Z. Now, we do recommend continuing the dose on schedule with no holding.”
Continuing medications considered low risk for use during pregnancy, such as 5-amino salicylic acids, sulfasalazine, thiopurines, and all monoclonal antibodies during preconception, pregnancy, and lactation, was also recommended.
However, small-molecule drugs such as S1P receptor molecules and JAK inhibitors should be avoided for at least 1 month, and in some cases for 3 months prior to attempting conception, unless there is no alternative for the health of the mother. They should also be avoided during lactation.
Grade statement 33, which suggests that live rotavirus vaccine may be provided in children with in utero exposure to biologics, is also new, Mahadevan noted. “All prior recommendations were that no live vaccine should be given in the first 6 months or longer if infants were exposed to biologics in utero, but based on a prospective Canadian study, there is no harm when given to these infants.”
Another novel recommendation is that women with IBD on any monoclonal antibodies, including newer interleukin-23s, may breastfeed even though there are not clinical trial data at this point. The recommendation to continue them through pregnancy and lactation is based on placental physiology, as well as on the physiology of monoclonal antibody transfer in breast milk, according to the consortium.
Furthermore, the authors noted, there was no increase in infant infections at 4 months or 12 months if they were exposed to a biologic or thiopurine (or both) during pregnancy.
Overall, the consortium recommended that all pregnancies for women with IBD be considered as “high risk” for complications. This is due to the fact that many parts of the world, including the US, are “resource-limited,” Mahadevan explained. Since maternal fetal medicine specialists are not widely available, the consortium suggested all these patients be followed with increased monitoring and surveillance based on available resources.
In addition to the guidelines, patient videos in seven languages, a professional slide deck in English and Spanish, and a video on the global consensus are all available at https://pianostudy.org/.
This study was funded by The Leona B. and Harry H. Helmsley Charitable Trust.
Mahadevan reported being a consultant for AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Enveda, Gilead, Janssen, Lilly, Merck, Pfizer, Protagonist, Roivant, and Takeda.
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
GI Disorders Linked With Sleep Problems
“Emerging evidence suggests a bidirectional relationship between GI diseases and sleep disorders, whereby dysfunction in one domain may exacerbate the other,” wrote Shicheng Ye, PhD, of The Third Clinical Medical College of Guangzhou University of Chinese Medicine, and colleagues. However, previous studies on the association between GI and sleep problems have been small, and the role of depression as a mediator has not been well explored.
In the study, which was published online in BMC Gastroenterology, the researchers reviewed data from the US National Health and Nutrition Examination Survey between 2005 and 2014. The study population included 10,626 adults aged 20 years or older, with a mean age of 45.6 years, 50.8% of whom were women. Of these, 6444 were identified as having GI disease on the basis of a “yes” response to the question of whether they had a stomach or intestinal illness with vomiting or diarrhea within the past 30 days.
Researchers also examined responses to survey questions related to sleep duration, trouble sleeping, and diagnosis of a sleep disorder. Individuals with vs without GI diseases had a significantly higher prevalence of sleep trouble (37.99% vs 24.21%; P < .001) and a greater frequency of diagnosed sleep disorders (14.99% vs 8.08%; P < .001).
An analysis adjusted for demographic, lifestyle, and clinical factors found that individuals with vs without GI diseases were 70% more likely to have sleep trouble. Individuals with vs without GI diseases were also significantly more likely to have a diagnosed sleep disorder and a reduction in sleep duration (adjusted odds ratio, 1.8; adjusted beta, -0.15).
The association between GI diseases and sleep problems remained consistent across individuals of multiple subgroups, including those without hypertension, diabetes, or a history of smoking. It also remained significant among individuals with coronary heart disease and higher scores on the dietary index for gut microbiota. No significant interaction effects related to age, sex, or chronic disease appeared in any subgroup (P > .05).
An additional mediation analysis found that depression partly mediated the associations between GI diseases and sleep issues. Depression accounted for 21.29% of the total effect on sleep problems, 19.23% of the effect on sleep disorders, and 26.68% of the effect on sleep duration.
The mediating role of depression on the association between GI disease and sleep problems may not be exclusive, the researchers wrote. Other potential mechanisms may include systemic inflammation, visceral hypersensitivity, and metabolic dysfunction.
The findings were limited by several factors, including the possibly underpowered sample size for machine-learning models and the reliance on self-reports of GI diseases, sleep outcomes, and coronary heart disease, the researchers noted. Other limitations included the inability to adjust for confounding factors, including obstructive sleep apnea, chronic pain, and hypertension.
However, the results illustrate the need to address both psychological and GI factors in clinical practice to improve sleep health, the researchers wrote. More research is needed to identify causal pathways and develop targeted, multidimensional interventions for this interconnected trio of health problems.
Increasing Evidence for Gut-Brain Interaction
Both sleep disorders and disorders of GBI (DGBI) are highly prevalent worldwide, Jatin Roper, MD, gastroenterologist and associate professor of medicine at Duke University, Durham, North Carolina, told GI & Hepatology News.
“A growing body of evidence suggests that DGBI, including irritable bowel syndrome, are caused by imbalances in signaling between the brain and the intestine, which include the vagus nerve, hormonal signals, the gut microbiota, and immune system,” said Roper, who was not involved in the current study.
“Since many sleep disturbances are centrally mediated, it is plausible that sleep and gastrointestinal disorders could be mechanistically linked,” he said. Rigorous analysis of patient databases for a possible association between sleep and GI disorders, as was done in the current study, is an important step.
The current study findings were not unexpected, “particularly the finding that depression may mediate a link between sleep and GI disorders, because depression is well known to be associated to sleep disturbances and DGBI,” Roper said.
However, GI doctors often do not ask patients about problems with sleep, and pulmonary doctors or sleep specialists may not ask patients about GI symptoms, Roper noted. Similarly, patients may not bring up all their symptoms when seeing these specialists.
“The current study underscores the need for comprehensive, multisystem evaluations in specialty clinics for sleep and GI conditions and appropriate referrals to specialists, when necessary,” he said.
The research raised an important question of whether sleep and GI disorders are associated with each other because of other underlying medical conditions, which may be difficult to control for in cross-sectional studies, or whether sleep problems cause GI problems or vice versa, Roper said. Other uncertainties include whether the conditions are biologically linked, possibly through shared changes in the brain-gut axis.
Long-term observational studies would be useful to identify whether sleep disturbances precede DGBI or vice versa, Roper added.
The study received no outside funding. The researchers and Roper had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
“Emerging evidence suggests a bidirectional relationship between GI diseases and sleep disorders, whereby dysfunction in one domain may exacerbate the other,” wrote Shicheng Ye, PhD, of The Third Clinical Medical College of Guangzhou University of Chinese Medicine, and colleagues. However, previous studies on the association between GI and sleep problems have been small, and the role of depression as a mediator has not been well explored.
In the study, which was published online in BMC Gastroenterology, the researchers reviewed data from the US National Health and Nutrition Examination Survey between 2005 and 2014. The study population included 10,626 adults aged 20 years or older, with a mean age of 45.6 years, 50.8% of whom were women. Of these, 6444 were identified as having GI disease on the basis of a “yes” response to the question of whether they had a stomach or intestinal illness with vomiting or diarrhea within the past 30 days.
Researchers also examined responses to survey questions related to sleep duration, trouble sleeping, and diagnosis of a sleep disorder. Individuals with vs without GI diseases had a significantly higher prevalence of sleep trouble (37.99% vs 24.21%; P < .001) and a greater frequency of diagnosed sleep disorders (14.99% vs 8.08%; P < .001).
An analysis adjusted for demographic, lifestyle, and clinical factors found that individuals with vs without GI diseases were 70% more likely to have sleep trouble. Individuals with vs without GI diseases were also significantly more likely to have a diagnosed sleep disorder and a reduction in sleep duration (adjusted odds ratio, 1.8; adjusted beta, -0.15).
The association between GI diseases and sleep problems remained consistent across individuals of multiple subgroups, including those without hypertension, diabetes, or a history of smoking. It also remained significant among individuals with coronary heart disease and higher scores on the dietary index for gut microbiota. No significant interaction effects related to age, sex, or chronic disease appeared in any subgroup (P > .05).
An additional mediation analysis found that depression partly mediated the associations between GI diseases and sleep issues. Depression accounted for 21.29% of the total effect on sleep problems, 19.23% of the effect on sleep disorders, and 26.68% of the effect on sleep duration.
The mediating role of depression on the association between GI disease and sleep problems may not be exclusive, the researchers wrote. Other potential mechanisms may include systemic inflammation, visceral hypersensitivity, and metabolic dysfunction.
The findings were limited by several factors, including the possibly underpowered sample size for machine-learning models and the reliance on self-reports of GI diseases, sleep outcomes, and coronary heart disease, the researchers noted. Other limitations included the inability to adjust for confounding factors, including obstructive sleep apnea, chronic pain, and hypertension.
However, the results illustrate the need to address both psychological and GI factors in clinical practice to improve sleep health, the researchers wrote. More research is needed to identify causal pathways and develop targeted, multidimensional interventions for this interconnected trio of health problems.
Increasing Evidence for Gut-Brain Interaction
Both sleep disorders and disorders of GBI (DGBI) are highly prevalent worldwide, Jatin Roper, MD, gastroenterologist and associate professor of medicine at Duke University, Durham, North Carolina, told GI & Hepatology News.
“A growing body of evidence suggests that DGBI, including irritable bowel syndrome, are caused by imbalances in signaling between the brain and the intestine, which include the vagus nerve, hormonal signals, the gut microbiota, and immune system,” said Roper, who was not involved in the current study.
“Since many sleep disturbances are centrally mediated, it is plausible that sleep and gastrointestinal disorders could be mechanistically linked,” he said. Rigorous analysis of patient databases for a possible association between sleep and GI disorders, as was done in the current study, is an important step.
The current study findings were not unexpected, “particularly the finding that depression may mediate a link between sleep and GI disorders, because depression is well known to be associated to sleep disturbances and DGBI,” Roper said.
However, GI doctors often do not ask patients about problems with sleep, and pulmonary doctors or sleep specialists may not ask patients about GI symptoms, Roper noted. Similarly, patients may not bring up all their symptoms when seeing these specialists.
“The current study underscores the need for comprehensive, multisystem evaluations in specialty clinics for sleep and GI conditions and appropriate referrals to specialists, when necessary,” he said.
The research raised an important question of whether sleep and GI disorders are associated with each other because of other underlying medical conditions, which may be difficult to control for in cross-sectional studies, or whether sleep problems cause GI problems or vice versa, Roper said. Other uncertainties include whether the conditions are biologically linked, possibly through shared changes in the brain-gut axis.
Long-term observational studies would be useful to identify whether sleep disturbances precede DGBI or vice versa, Roper added.
The study received no outside funding. The researchers and Roper had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
“Emerging evidence suggests a bidirectional relationship between GI diseases and sleep disorders, whereby dysfunction in one domain may exacerbate the other,” wrote Shicheng Ye, PhD, of The Third Clinical Medical College of Guangzhou University of Chinese Medicine, and colleagues. However, previous studies on the association between GI and sleep problems have been small, and the role of depression as a mediator has not been well explored.
In the study, which was published online in BMC Gastroenterology, the researchers reviewed data from the US National Health and Nutrition Examination Survey between 2005 and 2014. The study population included 10,626 adults aged 20 years or older, with a mean age of 45.6 years, 50.8% of whom were women. Of these, 6444 were identified as having GI disease on the basis of a “yes” response to the question of whether they had a stomach or intestinal illness with vomiting or diarrhea within the past 30 days.
Researchers also examined responses to survey questions related to sleep duration, trouble sleeping, and diagnosis of a sleep disorder. Individuals with vs without GI diseases had a significantly higher prevalence of sleep trouble (37.99% vs 24.21%; P < .001) and a greater frequency of diagnosed sleep disorders (14.99% vs 8.08%; P < .001).
An analysis adjusted for demographic, lifestyle, and clinical factors found that individuals with vs without GI diseases were 70% more likely to have sleep trouble. Individuals with vs without GI diseases were also significantly more likely to have a diagnosed sleep disorder and a reduction in sleep duration (adjusted odds ratio, 1.8; adjusted beta, -0.15).
The association between GI diseases and sleep problems remained consistent across individuals of multiple subgroups, including those without hypertension, diabetes, or a history of smoking. It also remained significant among individuals with coronary heart disease and higher scores on the dietary index for gut microbiota. No significant interaction effects related to age, sex, or chronic disease appeared in any subgroup (P > .05).
An additional mediation analysis found that depression partly mediated the associations between GI diseases and sleep issues. Depression accounted for 21.29% of the total effect on sleep problems, 19.23% of the effect on sleep disorders, and 26.68% of the effect on sleep duration.
The mediating role of depression on the association between GI disease and sleep problems may not be exclusive, the researchers wrote. Other potential mechanisms may include systemic inflammation, visceral hypersensitivity, and metabolic dysfunction.
The findings were limited by several factors, including the possibly underpowered sample size for machine-learning models and the reliance on self-reports of GI diseases, sleep outcomes, and coronary heart disease, the researchers noted. Other limitations included the inability to adjust for confounding factors, including obstructive sleep apnea, chronic pain, and hypertension.
However, the results illustrate the need to address both psychological and GI factors in clinical practice to improve sleep health, the researchers wrote. More research is needed to identify causal pathways and develop targeted, multidimensional interventions for this interconnected trio of health problems.
Increasing Evidence for Gut-Brain Interaction
Both sleep disorders and disorders of GBI (DGBI) are highly prevalent worldwide, Jatin Roper, MD, gastroenterologist and associate professor of medicine at Duke University, Durham, North Carolina, told GI & Hepatology News.
“A growing body of evidence suggests that DGBI, including irritable bowel syndrome, are caused by imbalances in signaling between the brain and the intestine, which include the vagus nerve, hormonal signals, the gut microbiota, and immune system,” said Roper, who was not involved in the current study.
“Since many sleep disturbances are centrally mediated, it is plausible that sleep and gastrointestinal disorders could be mechanistically linked,” he said. Rigorous analysis of patient databases for a possible association between sleep and GI disorders, as was done in the current study, is an important step.
The current study findings were not unexpected, “particularly the finding that depression may mediate a link between sleep and GI disorders, because depression is well known to be associated to sleep disturbances and DGBI,” Roper said.
However, GI doctors often do not ask patients about problems with sleep, and pulmonary doctors or sleep specialists may not ask patients about GI symptoms, Roper noted. Similarly, patients may not bring up all their symptoms when seeing these specialists.
“The current study underscores the need for comprehensive, multisystem evaluations in specialty clinics for sleep and GI conditions and appropriate referrals to specialists, when necessary,” he said.
The research raised an important question of whether sleep and GI disorders are associated with each other because of other underlying medical conditions, which may be difficult to control for in cross-sectional studies, or whether sleep problems cause GI problems or vice versa, Roper said. Other uncertainties include whether the conditions are biologically linked, possibly through shared changes in the brain-gut axis.
Long-term observational studies would be useful to identify whether sleep disturbances precede DGBI or vice versa, Roper added.
The study received no outside funding. The researchers and Roper had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
Intestinal Methanogen Overgrowth Fosters More Constipation, Less Diarrhea
, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.
“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care.
Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation.
The Study
To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.
Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6.
Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).
In other findings:
- Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
- They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
- Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
- Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.
Mechanism of Action
The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.
Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.
“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.
This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.
Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.
, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.
“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care.
Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation.
The Study
To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.
Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6.
Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).
In other findings:
- Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
- They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
- Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
- Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.
Mechanism of Action
The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.
Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.
“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.
This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.
Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.
, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.
“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care.
Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation.
The Study
To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.
Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6.
Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).
In other findings:
- Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
- They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
- Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
- Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.
Mechanism of Action
The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.
Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.
“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.
This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.
Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY