Tag Archives: IBS

Phase 3 Trial: Fecal Microbiota Transplantation Fails in IBS

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PH Johnsen et al. The Lancet, 2026 (published online September 24, 2026) https://doi.org/10.1016/S0140-6736(26)01424-8 Faecal microbiota transplantation in irritable bowel syndrome (REFIT2): a randomised, double-blind, placebo-controlled, phase 3 trial

Methods: This was a randomised, double-blind, multicentre study at five hospitals in Norway. Participants (median age 36 years, 65% women) were randomly assigned 2:1 to faecal microbiota transplantation (FMT) with faeces samples from either healthy donors (intervention, n=298) or the participants themselves (placebo group, n=150). All participants had baseline screening including prior colonoscopy. At baseline, the intervention group had 38% receiving a low FODMAP diet compared to 39% in the placebo group. There was also a similar degree of IBS severity: 93% and 96% had moderate-to-severe IBS, respectively. Each participant received one retention enema (60 g faeces); in the intervention group, the enema consisted of faeces from one of three donors.

Key findings:

  • 119 (40%) participants in the donor FMT group and 57 (38%) in the placebo group showed an improvement of at least 75 points on the IBS-SSS at 90 days after treatment.
  • The proportion of participants with adverse events was similar in the two study groups; however, the six serious adverse events all occurred in the donor FMT group; these included diverticulitis, cholecystitis, escalation of psychiatric condition, and appendicitis.
  • At 90 days after treatment, recipients of donor faecal microbiota transplantation showed a significant change in relative microbial abundance compared with baseline, and both relative microbial abundance and alpha diversity were significantly different in the intervention and placebo groups.
Treatment success at 90 days and 365 days follow-up. Treatment success defined as a 75-point drop in IBS-SSS score compared with baseline. IBS-SSS=Irritable Bowel Syndrome-Severity Scoring System.

Discussion points:

  • “Some earlier trials have reported clinical benefits of faecal microbiota transplantation in IBS; however, many studies have been limited by small sample sizes, single-donor designs, and less stringent endpoint definitions or did not allow for a robust assessment of donor-dependent effects… Although the gut microbiota might still contribute to IBS pathophysiology,
    these findings indicate that non-specific microbiota replacement strategies are unlikely to provide consistent therapeutic benefit.”
  • “The strengths of the current trial were the large sample size, rigorous design with double-blinding, random assignment of participants by donor, and multicentre recruitment.”
  • Limitations: “The reliance on patient-reported outcome measures is an inherent limitation in IBS trials, as few objective measures are available to assess clinical effects.”

My take (borrowed from the authors): “This phase 3 trial did not show any clinical benefit of
faecal microbiota transplantation for treating patients with moderate or severe IBS.”

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Food for Thought: Studies of Food Intake and IBS and DGBI

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In the first article by Jaafari et al, the authors identified four predominant food cluster patterns from 54,127 participants from 26 countries who completed online questionnaires. The highest prevalence of IBS was associated with cluster A (including Egypt, Brazil, and Colombia) and the lowest with cluster D from several Asian countries. Cluster A dietary pattern was “rich in FODMAPs.” Cluster D participants reported the highest frequencies of fish, rice and tofu consumption and lowest milk consumption (which could be due to higher rates of lactose intolerance). The limitations from this study include the reliance on a questionnaire, the small number of foods surveyed (10), and cultural differences in reporting symptoms.

The study by Mikhael-Moussa et al examined carbohydrate malabsorption, based on breath testing, in patients diagnosed with disorders of gut-brain interaction (DGBI). Patients completed questionnaires as well.

Key findings:

  • Among the 301 patients with DGBI included in our analysis, 178 (59.1%) had carbohydrate intolerance
  • Carbohydrate-intolerant patients were significantly more likely to be female (P value < 0.001), to have 2 or more DGBI (P value = 0.001) to have lactose maldigestion (P value< 0.001) and fructose malabsorption (P value = 0.023), higher irritable bowel syndrome and somatic symptom severity, and lower quality of life (P value < 0.001) compared with patients without carbohydrate intolerance

Discussion:

  • There are multiple potential reasons why certain foods can contribute to GI symptoms including malabsorption, gastrointestinal mobility, alterations in intestinal microbiota, intestinal distention, fluid accumulation, and localized IgE-dependent reactions (noted with confocal laser endomicroscopy).
  • “Carbohydrate-reduced diets have been found effective in reducing symptoms in patients, regardless of the presence of maldigestion/malabsorption”

My take: Dietary triggers are important for the majority of patients with IBS. In this study, patients with documented carbohydrate malabsorption had increased severity of their symptoms.

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ACupuncTure for Irritable bOwel syNdrome (ACTION)

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J-W Yang et al. Gastroenterology, Volume 169, Issue 5, 958 – 969.e5. Open Acces! Efficacy of ACupuncTure in Irritable bOwel syNdrome (ACTION): A Multicenter Randomized Controlled Trial

This ACTION study enrolled 280 patients (18-75 yrs) with IBS-D in a multicenter randomized controlled trial in 6 hospitals in China. “For the sham acupuncture group, blunt-tipped placebo needles with a similar appearance to real needles were used over the adhesive pads with no skin penetration. Five fixed pairs of non-acupoints (10 stimulation points in total) away from meridians or conventional acupoints were used.”

Key finding:

  • The primary outcome (see below) was reached by 71 (57.9%) patients in the acupuncture group compared with 47 (41.4%) patients in the sham acupuncture group (risk ratio 1.40; P = .008)
  • The effects of acupuncture in symptomatic improvements of IBS-D persisted 3 months after treatment with minimal to no side effects
  • Limitations including the difficulty of acupuncture blinding (despite the identical treatment setups)

My take: Acupuncture, especially given its safety, is a reasonable therapy for IBS-D; though, it is not recommended in recent pediatric guidelines. “The rub” in many locations is finding qualified practitioners.

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When Celiac Disease Symptoms Continue Despite a Gluten Free Diet

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A Kruegger et al. JPGN 2025; 81:596–605. Open Access! The prevalence and predictive factors of overlapping disorders of gut–brain interaction and celiac disease in children

Methods: Single-center, retrospective study of children (4–21 years old, n=191) with biopsy-proven Celiac disease (CeD) who were evaluated for DGBI based on Rome IV criteria. Patients who were adherent to a GFD, demonstrated tissue transglutaminase immunoglobulin A (TTG IgA) decline, and had at least one visit 9–24-months after diagnosis with a pediatric gastroenterologist. For this study, sustained TTG IgA decline required at least two declining TTG IgA values, a 90% decline from baseline, or normalization of TTG IgA.

Key findings:

  • 43% (n = 83) met Rome IV DGBI diagnostic criteria.
  • Functional constipation (27/83, 33%) and functional abdominal pain (24/83, 29%) were the most common DGBI
  • Abdominal pain, constipation, and vomiting at initial presentation as well as comorbid joint hypermobility, headaches, and chronic musculoskeletal pain increased risk of developing DGBI after serological decline

Discussion Points:

  • “The prevalence reported here is similar to a study of adults with CeD who were adherent to a GFD that reported over 50% met criteria for a functional gastrointestinal disorder19 and is higher than previously reported pediatric prevalence rates”
  • “The majority of patients who met DGBI criteria did so through having the persistence of the same gastrointestinal symptoms that were present at CeD diagnosis. This raises the question as to whether the symptoms at presentation were due to CeD, DGBI, or both”
  • “Clinicians could consider discussing that while symptoms related to CeD should improve on a GFD, some symptoms may persist, especially if they have an increased likelihood of having a comorbid DGBI. Such counseling may prevent the misattribution of persistent symptoms to ongoing gluten exposure and mitigate hypervigilance”
  • “Having complete villous blunting on diagnostic biopsy increased the likelihood of having a DGBI. Intuitively, it is possible that complete villous blunting can lead to greater nerve sensitization and subsequently higher rates of DGBI. It is also possible that complete villous blunting is slower to recover”

My take: Given the overlap of DGBI symptoms with CeD, diagnosing DGBI in patients with CeD can be challenging. However, DGBI is much more likely to contribute to lingering symptoms than refractory CeD.

As a practical matter, the high frequency of ongoing GI symptoms despite use of a GFD provides another drawback to relying on a no-biopsy diagnosis. A no-biopsy diagnosis introduces greater uncertainty in the diagnosis and does not allow for a histologic comparison if a subsequent evaluation is needed.

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Claude Monet, Bridge over a Pond of Water Lilies at The Metropolitan Museum of Art

IBS Impact: Survey Reveals Daily Life Struggles

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AGA GastroNews, AGA IBS in America survey reveals IBS major burden despite advances in treatment (8/7/25):

Methods: The Harris Poll on behalf of AGA in 2024, among 2,013 U.S. adults age 18+ who have been diagnosed by a health care provider with IBS-C (1,005) or IBS-D (1,008). In addition, U.S. health care provider research was conducted online among 600 health care providers including gastroenterologists (n=200), primary care physicians (PCPs, n=200), gastroenterology nurse practitioners (NP)/physician assistants (PA) (n=100), and PCP NP/PAs (n=100)

Key findings:

  • IBS symptoms interfere with patients’ productivity at work/school for nearly 11 days per month on average
  • IBS symptoms disrupt personal activities eight days per month on average
  • 69% say their symptoms make them feel like they’re not “normal”
  • 77% avoid situations where bathroom access is limited.
  • 72% find it difficult to plan activities due to unpredictable symptoms.
  • 72% stay home more often because of their symptoms

My take: This sample of patients with IBS likely has more severe symptoms than a more general population of patients with IBS. Nevertheless, it highlights the impact of IBS symptoms on daily living.

Link: AGA IBS Toolkit

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Westminster Abbey, London


Pilot Study: Mediterranean Diet vs Low FODMAP for Irritable Bowel Syndrome

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S Singh et al. Neurogastroenterology and Motility 2025; https://doi.org/10.1111/nmo.70060. Open Access! Efficacy of Mediterranean Diet vs. Low-FODMAP Diet in Patients With Nonconstipated Irritable Bowel Syndrome: A Pilot Randomized Controlled Trial

Methods: Patients were randomized controlled trial (RCT), adult patients with diarrhea-predominant IBS (IBS-D) or mixed bowel pattern (IBS-M) were randomized to Mediterranean diet (MD) versus a diet low in fermentable oligo-, di-, monosaccharides, and polyols (LFD) for 4 weeks. 10 patients completed the study in each group. The primary endpoint was the proportion of patients with ≥ 30% decrease in abdominal pain intensity (API) for ≥ 2/4 weeks. Daily variables included abdominal pain intensity (API) and bloating, while IBS symptom severity score (IBS-SSS) and IBS adequate relief (IBS-AR) were scored weekly

Key findings:

  • 73% percent of the MD group met the primary endpoint compared to 81.8% of the LFD group (p = 1.0)
  • Although not statistically significant, a numerically higher proportion of the LFD group reported adequate relief and met the responder endpoint for IBS-SSS (50-point reduction) compared to the MD group (54.6% vs. 27.3% for IBS-AR and 81.8% vs. 45.5% for IBS-SSS, p = 0.39 and 0.18, respectively)
  • The LFD group also had a significantly greater reduction in IBS-SSS score over the 4-week treatment period compared to the MD group (−105.5 vs. −60, p = 0.02)

My take (borrowed from authors): A Mediterannean diet “improves abdominal symptoms in the majority of patients with IBS-D and IBS-M. Larger, adequately powered, real-world studies comparing the efficacy of a MD with LFD and NICE diet are needed to validate these preliminary findings and to help patients and providers to know if a MD should be added to the list of effective, evidence-based diet interventions for patients with IBS.”

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New Study: Leaky Gut and Irritable Bowel Syndrome

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MR Barbaro et al. Gastroenterol 2024; 167: 1152-1166. Molecular Mechanisms Underlying Loss of Vascular and Epithelial Integrity in Irritable Bowel Syndrome

This study examined markers of the epithelial and vascular barriers in 223 patients with irritable bowel syndrome in comparison to 78 healthy subjects. In actuality, this lengthy report was a composite of about 8 different experiments.

Key findings:

  • Figure 2 summarizes in vivo and in vitro epithelial permeability testing using orally-administered sugars and using Caco-2 cell incubation of control/IBS supernatants. In all of these experiments, there was a significant mean increase in IBS-D permeability compared to controls.
  • Figures 3 and 4 report on significant changes the gut vascular barrier and specific mediators, respectively, in IBS compared to controls
  • One novel finding was correlation of epithelial barrier markers with gastrointestinal symptoms and gut vascular dysfunction with systemic systems including anxiety and depression (see heat map below)
Relationships between epithelial and endothelial permeability markers and symptoms. The asterisks on the heatmap indicate significances in the Spearman’s correlation.

My take: The term ‘leaky gut’ has a negative connotation among many gastroenterologists as it has been associated with misleading diagnostic and therapeutic claims. However, this study shows a correlation between epithelial and vascular barrier disruptions and symptoms in irritable bowel. This is useful information; nevertheless, there are not simple tests to identify these findings and there are not therapeutics with demonstrated efficacy.

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“Efficacy” of Probiotics in Irritable Bowel Syndrome

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VC Goodoory, M Khasawneh et al. Gastroenterol 2023; 165: 1206-1218. Open Access! Efficacy of Probiotics in Irritable Bowel Syndrome: Systematic Review and Meta-analysis

After performing a systematic literature review, the authors identified randomized controlled trials (RCTs) recruiting adults with IBS, comparing probiotics with placebo were eligible; this included 82 eligible trials, containing 10,332 patients. However, only 24 RCTs were at low risk of bias across all domains.

Key findings:

  • There was some evidence to support the use of some probiotics for global IBS symptoms, abdominal pain, and abdominal bloating or distension (highly detailed analysis of the studies in article –Figures 1-3 and Tables 1-3)
  • There was moderate certainty in the evidence for a benefit of Escherichia strains, low certainty for Lactobacillus strains and L. plantarum 299V, and very low certainty for combination probiotics, LacClean Gold S, Duolac 7s, and Bacillus strains
  • For abdominal pain, there was low certainty in the evidence for a benefit of S. cerevisiae I-3856 and Bifidobacterium strains, and very low certainty for combination probiotics, Lactobacillus, Saccharomyces, and Bacillus strains
  • For abdominal bloating or distension, there was very low certainty in the evidence for a benefit of combination probiotics and Bacillus strains
  • The relative risk of experiencing any adverse event, in 55 trials, including more than 7000 patients, was not significantly higher with probiotics

My take: This study shows that it is difficult to confidently recommend specific probiotics for IBS as the certainty in the evidence for efficacy by GRADE criteria was low to very low. In addition, the quality control of production of most probiotics is uncertain.

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Increased bile acids in diarrhea-predominant IBS

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The role for bile acids in causation of irritable bowel gets a closer look in a recent publication (Clin Gastroenterol Hepatol 2012; 10: 1009-15).

This study randomly selected 52 participants (26 with diarrhea-predominant IBS, 26 with constipation predominant IBS) from a cohort of 700 IBS patients followed at the Mayo clinic along with 26 healthy volunteers.  The ages of the patients ranged from 29-51. Subsequently, these patients underwent additional testing following a 4-day high fat diet.  Of note, 5 of the IBS-D patients had a history of cholecystectomy compared with one patient in the other two groups.

In these patients, bile acid concentrations were measured in the stool and serum levels of 7α-hydroxy-4-cholesten-3-one (C4).In the IBS-D patients, serum levels of C4 were significantly higher than in the other two groups.  38% of the IBS-D group had elevated C4 levels; these elevated levels correlated with increased stool concentrations of bile acids.

The authors note that bile acid malabsorption has been identified frequently in patients with unexplained chronic diarrhea and that these patients often respond to bile acid sequestration (eg. cholestyramine or colesevelam).  Another interesting finding was that obesity was associated with elevated bile acid levels. Overall, the cohort with IBS-D had an average BMI of 29.5.

So, what conclusions can be drawn?

  • Serum C4 levels may be using in identifying patients with bile acid malabsorption
  • Bile acid sequestration agents may be worth a try in some cases of IBS-D and this study provides a rationale

Additional references:

-Alim Pharmacol Ther 2009; 30: 707-17.  Bile acid malabsorption in IBS-D.

Food choices, FODMAPs, and gluten haters

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Given the frequency of functional gastrointestinal diseases (FGID), including irritable bowel syndrome (IBS), dietary treatments that may improve symptoms receive a lot of attention.  A recent review of the role of food choices in the development and management of FGIDs is a useful reference (Am J Gastroenterol 2012; 107: 657-66 -thanks to Ben Gold for forwarding this article).

This review details specific dietary advice as well as the following specific physiologic effects of FODMAPs:

  • Osmotic effects
  • Bacterial fermentation
  • Motility effects
  • Prebiotic effects
  • Systemic effects –mild depression, tiredness
In addition, the review looks at other potential foods which could serve as a trigger for IBS symptoms, like gluten & summarizes why some IBS patients are gluten haters.  The authors acknowledge that gluten sensitivity, in the absence of celiac disease, does not have a known mechanism.  Until a reliable marker becomes available, the importance of gluten sensitivity for FGIDs is unknown.
Related posts:

What to make of FODMAPs

Gluten sensitivity without celiac disease

Is a biopsy necessary in Celiac disease?