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The microbiome in IBS

TL;DR — This is the largest mechanistic sub-literature in IBS (2,797 PubMed records for irritable bowel syndrome AND (microbiome OR microbiota) on 2026-09-02) and the one with the least clinical yield. Composition differences replicate at the level of taxa: Enterobacteriaceae, Lactobacillaceae and Bacteroides increased; uncultured Clostridiales I, Faecalibacterium (including F. prausnitzii) and Bifidobacterium decreased; diversity decreased or unchanged (Pittayanon 2019, PMID 30940523, 24 studies) — and a uniform re-analysis of 1,167 faecal 16S samples from 9 studies found significantly lower alpha diversity and 26 discriminating genera (Li 2024, PMID 39777150). What has not happened is translation. No microbiome test is used diagnostically; probiotic efficacy is strain-specific and rated low-to-very-low certainty by GRADE across almost every analysis of 82 trials and 10,332 patients (Goodoory 2023, PMID 37541528); and faecal microbiota transplantation has produced the single most spectacular positive trial in the field (response 89.1% with 60 g FMT vs 23.6% placebo; El-Salhy 2020, PMID 31852769) alongside two well-conducted negatives (Lahtinen 2020, PMID 32343000; Yau 2023, PMID 37667968), with meta-analyses splitting on whether the pooled effect exists at all (RR 1.44, 0.88–2.33, very low certainty — Lo 2024, PMID 39289768 — versus OR 0.46, 0.33–0.64 in a Bayesian network meta-analysis — Wu 2024, PMID 38999862). A later powered phase 3 of a once-only healthy-donor versus autologous rectal enema was null on a stricter endpoint: 40% versus 38% reached a ≥75-point IBS-SSS reduction at 90 days (absolute difference 1.9 percentage points, 95% CI −8.1 to 12.0; p=0.76; Johnsen 2026, PMID 42785338). The causal question Pittayanon posed in 2019 — "whether these microbes are a product or cause of IBS" — is still open.

What replicates in composition

Direction in IBS Taxon Source
Increased Family Enterobacteriaceae (phylum Proteobacteria) Pittayanon 2019, PMID 30940523
Increased Family Lactobacillaceae Pittayanon 2019, PMID 30940523
Increased Genus Bacteroides Pittayanon 2019, PMID 30940523
Decreased Uncultured Clostridiales I Pittayanon 2019, PMID 30940523
Decreased Genus Faecalibacterium, incl. F. prausnitzii Pittayanon 2019, PMID 30940523
Decreased Genus Bifidobacterium Pittayanon 2019, PMID 30940523
Decreased or unchanged Alpha diversity Pittayanon 2019, PMID 30940523; significantly lower by random-effects model in Li 2024, PMID 39777150

Caveats attached to that table by its own authors: more than 40% of the included studies did not state whether cases and controls were comparable on sex and/or age (Pittayanon 2019, PMID 30940523). The 2024 pooled re-analysis added 26 genera and 12 predicted pathways with significant odds ratios and classification potential, and reported that Ruminococcaceae and Christensenellaceae correlated negatively with vitamin B6 metabolism, which was decreased in IBS (Li 2024, PMID 39777150). Mucosa-associated and faecal communities differ from each other and both differ from controls (Sundin 2020, PMID 31953505), so "the IBS microbiome" is at minimum two compartments. A further systematic review with meta-analysis has examined the immunological-status/dysbiosis interaction (Ahmed 2026, PMID 40903688).

None of these differences has been converted into a diagnostic. Eleven biomarkers "performed no better than symptom-based criteria" in the diagnostic accuracy literature (Sood 2015, PMID 26076071), and the 2026 review of serological and faecal markers reaches the same conclusion for the field as a whole (Burns 2026, PMID 41793943).

Probiotics: many trials, strain-level answers, low certainty

The definitive synthesis is 82 RCTs, 10,332 patients, of which only 24 were at low risk of bias across all domains (Goodoory 2023, PMID 37541528):

Outcome Evidence of benefit GRADE certainty
Global symptoms Escherichia strains Moderate
Global symptoms Lactobacillus strains; L. plantarum 299V Low
Global symptoms Combination probiotics, LacClean Gold S, Duolac 7s, Bacillus strains Very low
Abdominal pain Saccharomyces cerevisiae I-3856, Bifidobacterium strains Low
Abdominal pain Combination probiotics, Lactobacillus, Saccharomyces, Bacillus strains Very low
Bloating/distension Combination probiotics, Bacillus strains Very low
Adverse events (55 trials, >7,000 patients) No significant increase vs placebo —

A 2026 strain-specific meta-analysis of 32 articles covering 10 single strains found efficacy for Bifidobacterium longum (formerly B. infantis) 35624, Lactobacillus rhamnosus GG, Lactiplantibacillus plantarum 299v (DSM 9843), Saccharomyces cerevisiae CNCM I-3856 and Bacillus coagulans Unique IS2 (MTCC 5260); B. coagulans MTCC 5856 improved quality of life; results for Saccharomyces boulardii CNCM I-745 were conflicting; and it found no efficacy for Escherichia coli Nissle 1917, Lactobacillus gasseri BNR17 or Lactobacillus casei Shirota (Maslennikov 2026, PMID 41682832). Note the direct disagreement with Goodoory 2023, which rated Escherichia strains the highest-certainty benefit for global symptoms; the two reviews use different inclusion rules (single-strain-only versus all probiotics) and reach opposite conclusions about the same genus.

Earlier syntheses reached the same structural verdict from further back: "which particular combination, species or strains of probiotics are effective for IBS remains, for the most part, unclear," with sparse data for prebiotics and synbiotics (Ford 2018, PMID 30294792). A Bayesian network meta-analysis of 54 probiotic, 7 prebiotic/synbiotic and 6 FMT trials found probiotics favourable (OR 0.53, 0.48–0.59) and prebiotics/synbiotics not (Wu 2024, PMID 38999862).

The practical position: probiotics are safe, some strains probably help some patients, the evidence certainty is low, and no head-to-head trial identifies the best strain. Guidelines diverge accordingly (guidelines).

Gas-producing microtypes: the one compositional finding with a clinical correlate

The strongest link between composition and phenotype runs through gas metabolism rather than through taxa counts. Combining breath testing with 16S sequencing in IBS-C and IBS-D subjects drawn from two randomised trials (NCT03763175, NCT04557215), Villanueva-Millan and colleagues found (PMID 36114762):

Subtype Breath signature Microbial correlate
IBS-C Higher methane Higher microbial diversity; higher relative and absolute abundance of methanogens, predominantly Methanobrevibacter, including M. smithii; higher Ruminococcaceae and Christensenellaceae; metabolic pathways for methanogenesis and cofactor F420 biosynthesis enriched
IBS-D Higher hydrogen and hydrogen sulphide Lower microbial diversity; higher abundance of H₂S producers including Fusobacterium and Desulfovibrio; higher Enterobacteriaceae; sulfate-reduction pathways enriched

This is consistent with earlier work identifying Methanobrevibacter smithii as the predominant methanogen in constipation-predominant IBS with breath methane (Kim 2012, PMID 22573345; Ghoshal 2016, PMID 27458176), with methanogen overgrowth associating with delayed small-bowel and colonic transit on wireless motility capsule (Talamantes 2024, PMID 39068378), and with animal work in which hydrogen-sulphide producers drive a diarrhoea-like phenotype and a methane producer a constipation-like phenotype (Villanueva-Millan 2024, PMID 38060167). It also converges with the mechanistic finding inside a randomised FMT trial, where bloating improvement accompanied a fall in hydrogen-sulphide-producing pathways (Yau 2023, PMID 37667968).

Therapeutically this has generated one distinctive idea: targeting archaeal methanogenesis with statins, on the basis that lovastatin lactone inhibits enzymes in that pathway, with a modified-release formulation developed to reach intestinal methanogens (Gottlieb 2016, PMID 26559904; Muskal 2016, PMID 27347377; Hubert 2018, PMID 28989013). No phase 3 result was retrievable in this session's searches (searched 2026-09-02).

Metabolites: what is and is not altered

Analyte Finding Source
Blood serotonin (5-HT) Increased in IBS vs healthy controls, SMD 2.35 (95% CI 0.46–4.24), 5 studies Luo 2021, PMID 33407171
Total faecal short-chain fatty acids No significant difference, SMD −0.01 (−0.57 to 0.55) Luo 2021, PMID 33407171
Faecal acetate / propionate / butyrate −0.04 (−0.55 to 0.47) / 0.07 (−0.45 to 0.60) / −0.00 (−0.49 to 0.49) — all null Luo 2021, PMID 33407171
Faecal SCFAs across interventions Separately meta-analysed Ju 2024, PMID 38892659; Sun 2019, PMID 30762787
Colonic microbiome under low FODMAP Systematically reviewed and meta-analysed So 2022, PMID 35728042
Longitudinal omics Systematically reviewed Ng 2023, PMID 37110143

The null SCFA result matters because short-chain fatty acids are the usual mechanistic bridge between dietary fermentation and symptoms. The authors note their analysis did not differentiate IBS subgroups (Luo 2021, PMID 33407171), and the gas-microtype work above suggests why that may be fatal to the analysis: IBS-C and IBS-D appear to have opposite gas-metabolic profiles, so pooling them can cancel real differences.

The strain with the most direct evidence: Bifidobacterium longum (formerly infantis) 35624

Study Design Result
O'Mahony 2005, PMID 15765388 77 IBS patients randomised to Lactobacillus salivarius UCC4331, B. infantis 35624 (both 1×10¹⁰ cells in a malted milk drink) or the drink alone, 8 weeks B. infantis 35624 reduced composite and individual scores for abdominal pain/discomfort, bloating/distension and bowel-movement difficulty versus placebo for most treatment weeks; bowel frequency and consistency did not differ. Baseline IL-10/IL-12 ratio was abnormal (proinflammatory Th-1 pattern) and was normalised by B. infantis 35624 alone
Whorwell 2006, PMID 16863564 362 primary-care IBS patients, any subtype, randomised to placebo or encapsulated B. infantis at 1×10⁶, 1×10⁸ or 1×10¹⁰ cfu/mL for 4 weeks Only the 1×10⁸ dose beat placebo — on the primary endpoint of abdominal pain and on composite score, bloating, bowel dysfunction, incomplete evacuation, straining and gas passage; global symptom assessment exceeded placebo by >20% (p<0.02). Neither 1×10⁶ nor 1×10¹⁰ differed from placebo, and the highest dose had formulation problems
Yuan 2017, PMID 28166427 Meta-analysis of B. infantis 35624 trials Pooled synthesis
Ringel-Kulka 2017, PMID 27845337 Multicentre RCT in non-patients with abdominal discomfort and bloating Extends the strain beyond diagnosed IBS
Maslennikov 2026, PMID 41682832 Strain-specific meta-analysis B. longum (formerly B. infantis) 35624 among the strains with demonstrated efficacy

The Whorwell dose–response is the single most instructive probiotic result in this literature: the same organism was effective at one dose and indistinguishable from placebo at doses one hundred-fold above and below it. The authors' own conclusion — that clinical data are needed "in the final dosage form and dose" before products are used in practice — is routinely ignored by the commercial probiotic market. Broader probiotic reviews reach compatible conclusions (Brenner 2009, PMID 19277023; Charbonneau 2013, PMID 23549409).

Prospective selection by microbial metabolites

A newly posted McMaster pilot selects probiotics using screening metabolites: B. longum for higher lysophosphatidylcholine/lysophosphatidic acid (LPC/LPA), or a Lactobacillus probiotic for higher histamine. It plans 30 adults in randomized, participant- and investigator-masked n-of-1 crossovers against placebo over eight weeks; abdominal-pain VAS is the primary outcome. On 2026-10-14 it was enrolling by invitation, first posted 2026-10-13, with no registry results (NCT07872514, ClinicalTrials.gov API v2). This is prospective testing of treatment selection, not a validated diagnostic or demonstrated treatment effect.

Faecal microbiota transplantation: the field's sharpest contradiction

Trial n Design Primary outcome Result
El-Salhy 2020, PMID 31852769 (NCT03822299) 165 Placebo (own faeces) vs 30 g vs 60 g FMT from one well-characterised donor, via gastroscope ≥50-point IBS-SSS reduction at 3 months Response 23.6% / 76.9% (p<0.0001) / 89.1% (p<0.0001); dose–response; improvements in fatigue and QoL; mild self-limiting adverse events
Lahtinen 2020, PMID 32343000 (NCT03561519) 49 Autologous vs allogenic FMT via colonoscopy Sustained ≥50-point IBS-SSS reduction Not achieved in either group. Transient reduction at 12 weeks in the FMT arm vs baseline (p=0.01); microbiota shifted toward donor and stool water content fell; conclusion: single colonoscopic infusion "cannot be recommended"
Yau 2023, PMID 37667968 (NCT03125564) 56 (IBS-D) FMT vs placebo, duodenal route, baseline and week 4 >50-point IBS-SSS reduction at week 12 57.1% vs 46.4% (p=0.42) — negative. Bloating improved more with FMT (72% vs 30%, p=0.005), accompanied by reduced hydrogen-sulphide-producing pathway and Ruminococcus gnavus, enrichment of Lawsonibacter
Johnsen 2026, PMID 42785338 (NCT04691544; REFIT2) 448 analysed (450 enrolled) Healthy-donor vs autologous FMT, 2:1, once-only rectal enema, five Norwegian hospitals; Rome IV, IBS-SSS ≥175, ages 18–65 ≥75-point IBS-SSS reduction at 90 days 119 (40%) vs 57 (38%); absolute difference 1.9 percentage points (95% CI −8.1 to 12.0; p=0.76) — negative. Adverse-event proportions were similar; the abstract gives no counts. Full note: Johnsen 2026 — REFIT2
Cinek 2026, Research Square doi:10.21203/rs.3.rs-11289849/v1 (preprint, not peer reviewed); registry match NCT04899869 (MISCEAT) 61 randomised, 50 in efficacy analysis Three-arm double-blind crossover: multi-donor live FMT then autoclaved placebo FMT, the reverse sequence, or placebo twice; mixed high-diversity material from donors preselected by bacteriome; IBS-D or IBS-M adults Change in IBS-SSS 4 weeks after intervention Active vs autoclaved FMT effect 2.5 points (95% CI −33.6 to 38.6; p=0.893), negative. Live FMT raised bacterial diversity, shifted recipients toward donor composition and transferred donor-derived strains; no grade ≥3 adverse events

Meta-analysis has not resolved this. Twelve RCTs, 615 participants: no significant difference for clinical response (RR 1.44, 0.88–2.33), IBS-SSS (SMD −0.31, −0.72 to 0.09) or IBS-QOL (SMD 0.30, −0.09 to 0.69); subgroup analysis restricted to low-risk-of-bias studies using endoscopic, nasojejunal or rectal-enema delivery did show benefit; trial sequential analysis judged the evidence inconclusive and GRADE certainty very low (Lo 2024, PMID 39289768). A separate Bayesian network meta-analysis put FMT at OR 0.46 (0.33–0.64) in favour (Wu 2024, PMID 38999862). Other syntheses of the same trial set exist (Halkjær 2023, PMID 37346153).

The most plausible reading of the discordance, before REFIT2, was that FMT effect depends on donor, dose and route rather than on FMT as a category — which is El-Salhy's own explanation ("utilising a well-defined donor with a normal dysbiosis index and favourable specific microbial signature is essential"; PMID 31852769) and is exactly the kind of claim that a positive single-donor trial cannot itself establish. REFIT2 is a powered healthy-donor versus autologous comparison and it was null, so donor-versus-procedure does not by itself explain El-Salhy's result. It used a different route, an unstated dose in the abstract, and a ≥75-point rather than ≥50-point endpoint, and the response rates are not directly comparable. It still does not randomise recipients among multiple allogenic donors. A search on 2026-09-02 found no IBS trial that did so, and a date-restricted PubMed search from 2026-09-02 through 2026-09-30 found none either. A Czech crossover trial posted as a preprint on 2026-10-23 tested a different variable, pooled multi-donor material from bacteriome-preselected donors, and was also null on IBS-SSS. The FMT still engrafted: diversity rose and donor-derived strains were acquired (Cinek 2026, Research Square doi:10.21203/rs.3.rs-11289849/v1, preprint, not peer reviewed). The authors read it as suggesting "the futility of FMT in treating IBS". Pooling donors is not the same as randomising recipients among donors, so this does not close the gap above. It does separate engraftment from symptom benefit within one trial. The preprint abstract does not print a registration number. NCT04899869 (MISCEAT, Thomayer University Hospital; completed 2024-03-27; 61 enrolled; no results posted) matches it on author team, design and enrolment, and its protocol paper is Hurych 2022 (PMID 35760542). The full preprint text was not read. An accompanying commentary is indexed (Liu 2026, PMID 42785337); its abstract is empty, so no interpretation is taken from it. On 2026-09-30 ClinicalTrials.gov still listed NCT04691544 as active, not recruiting, with no results posted (last update 2024-02-26).

Antibiotic modulation

Rifaximin is the one antibiotic with replicated efficacy in non-constipated IBS (RR of symptoms persisting 0.84, 0.79–0.90, across five similarly designed trials; Ford 2018, PMID 30294792). Because its interpretation is entangled with the contested SIBO construct, it has its own page: rifaximin-and-the-sibo-question. Faecal bacterial composition has been reported to predict rifaximin response in IBS-D (Li 2020, PMID 32470562) — an unreplicated result that, if it held, would be the field's first actionable microbiome test.

Why the causal question is still open

  1. No human dose–response outside a single trial. El-Salhy's 30 g/60 g gradient (PMID 31852769) is the only dose–response evidence, from one donor, in one centre.
  2. Compositional differences are confounded by diet and transit. Low-FODMAP diet itself changes the microbiome (Staudacher 2021, PMID 33183883; Cox 2020, PMID 31586453), and transit time is a major determinant of stool composition — so cross-sectional differences between patients and controls cannot be read as aetiological.
  3. The successful interventions do not map onto the observed deficits. Bifidobacterium is depleted in IBS (Pittayanon 2019, PMID 30940523), yet Bifidobacterium supplementation has only low-certainty evidence for abdominal pain and none for global symptoms (Goodoory 2023, PMID 37541528).
  4. A positive-response mechanism has been proposed but not tested prospectively: reduction in hydrogen-sulphide-producing bacteria accompanied the bloating benefit in the Hong Kong FMT trial (Yau 2023, PMID 37667968).

What guidelines do with this

ACG and BSG treat probiotics cautiously and do not recommend routine microbiome testing; FMT is not recommended outside trials in the guidance retrieved for guidelines. No regulator has approved a microbiome-directed product for IBS as of 2026-09-02 (searched this session; absence stated as of that date).

Open questions

  • Is dysbiosis cause or consequence? Posed explicitly in 2019 (Pittayanon 2019, PMID 30940523) and unanswered in 2026.
  • Why does one FMT trial report an 89% response rate and the others report none (El-Salhy 2020, PMID 31852769; Lahtinen 2020, PMID 32343000; Yau 2023, PMID 37667968; Johnsen 2026, PMID 42785338)? REFIT2 was null on a ≥75-point endpoint after a single healthy-donor versus autologous enema, which weakens donor-versus-procedure as a sufficient explanation. No IBS trial randomising recipients among multiple allogenic donors was found on 2026-09-02 or in a date-restricted search through 2026-09-30. The abstract does not report a ≥50-point result. A pooled multi-donor crossover trial (preprint) was also null despite donor-strain engraftment (Cinek 2026, doi:10.21203/rs.3.rs-11289849/v1). That makes "engraftment without benefit" a separate question from donor selection.
  • Do Escherichia strains help or not? Goodoory 2023 (PMID 37541528) rates them the highest-certainty probiotic benefit; Maslennikov 2026 (PMID 41682832) finds E. coli Nissle 1917 ineffective.
  • Can faecal composition predict rifaximin response (Li 2020, PMID 32470562)? A single unreplicated report.
  • Is the depleted-Bifidobacterium/supplement-Bifidobacterium mismatch informative about mechanism, or does it simply mean transient colonisation does not restore function?
  • What does the hydrogen-sulphide pathway signal mean (Yau 2023, PMID 37667968)? It is the only mechanistic mediator identified inside a randomised IBS microbiome trial.
  • Does the methane/hydrogen-sulphide microtype framework generalise beyond the Cedars-Sinai trial populations (Villanueva-Millan 2022, PMID 36114762), and can it be used to allocate treatment?
  • Do statins targeting archaeal methanogenesis work in IBS-C? The rationale is developed (Gottlieb 2016, PMID 26559904). No phase 3 result was retrievable on 2026-09-02, and a date-restricted PubMed search from 2026-09-02 through 2026-09-30 still returned none.
  • Why are faecal short-chain fatty acids not different in IBS when fermentation is the presumed mechanism of dietary therapy (Luo 2021, PMID 33407171)? Is the null an artefact of pooling opposite subtypes?
  • Why did B. infantis 35624 work at 1x10^8 cfu but not at 1x10^6 or 1x10^10 (Whorwell 2006, PMID 16863564)? A hundred-fold dose window with no monotonic relationship is difficult to reconcile with a simple colonisation model.
  • Would a microbiome-stratified trial (treat only the dysbiotic) beat unstratified treatment? Never attempted.

References

  1. Pittayanon R, Lau JT, Yuan Y, Leontiadis GI, Tse F, Surette M, Moayyedi P. Gut Microbiota in Patients With Irritable Bowel Syndrome-A Systematic Review. Gastroenterology. 2019;157(1):97-108. PMID 30940523
  2. Li X, et al. Meta-analysis of gut microbiota alterations in patients with irritable bowel syndrome. Front Microbiol. 2024;15:1492349. PMID 39777150
  3. Sundin J, et al. Evidence of altered mucosa-associated and fecal microbiota composition in patients with Irritable Bowel Syndrome. Sci Rep. 2020;10(1):593. PMID 31953505
  4. Ahmed T, et al. The Interplay Between Immunological Status and Gut Microbial Dysbiosis in the Development of the Symptoms of Irritable Bowel Syndrome: A Systematic Review with Meta-Analysis. Dig Dis Sci. 2026;71(2):376-410. PMID 40903688
  5. Goodoory VC, Khasawneh M, Black CJ, Quigley EMM, Moayyedi P, Ford AC. Efficacy of Probiotics in Irritable Bowel Syndrome: Systematic Review and Meta-analysis. Gastroenterology. 2023;165(5):1206-1218. PMID 37541528
  6. Maslennikov R, et al. Strain-Specific Systematic Review with Meta-Analysis of Probiotics Efficacy in the Treatment of Irritable Bowel Syndrome. J Clin Med. 2026;15(3):1152. PMID 41682832
  7. Ford AC, Harris LA, Lacy BE, Quigley EMM, Moayyedi P. Systematic review with meta-analysis: the efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndrome. Aliment Pharmacol Ther. 2018;48(10):1044-1060. PMID 30294792
  8. Wu Y, Li Y, Zheng Q, Li L. The Efficacy of Probiotics, Prebiotics, Synbiotics, and Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis. Nutrients. 2024;16(13):2114. PMID 38999862
  9. El-Salhy M, Hatlebakk JG, Gilja OH, Bråthen Kristoffersen A, Hausken T. Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study. Gut. 2020;69(5):859-867. PMID 31852769
  10. Lahtinen P, et al. Randomised clinical trial: faecal microbiota transplantation versus autologous placebo administered via colonoscopy in irritable bowel syndrome. Aliment Pharmacol Ther. 2020;51(12):1321-1331. PMID 32343000
  11. Yau YK, et al. Randomised clinical trial: Faecal microbiota transplantation for irritable bowel syndrome with diarrhoea. Aliment Pharmacol Ther. 2023;58(8):795-804. PMID 37667968
  12. Lo SW, et al. Clinical efficacy and safety of faecal microbiota transplantation in the treatment of irritable bowel syndrome: a systematic review, meta-analysis and trial sequential analysis. Eur J Med Res. 2024;29(1):464. PMID 39289768
  13. Halkjær SI, et al. Fecal microbiota transplantation for the treatment of irritable bowel syndrome: A systematic review and meta-analysis. World J Gastroenterol. 2023;29(20):3185-3202. PMID 37346153
  14. Li Y, et al. Fecal bacteria can predict the efficacy of rifaximin in patients with diarrhea-predominant irritable bowel syndrome. Pharmacol Res. 2020;159:104936. PMID 32470562
  15. Staudacher HM, et al. Gut microbiota associations with diet in irritable bowel syndrome and the effect of low FODMAP diet and probiotics. Clin Nutr. 2021;40(4):1861-1870. PMID 33183883
  16. Cox SR, et al. Effects of Low FODMAP Diet on Symptoms, Fecal Microbiome, and Markers of Inflammation in Patients With Quiescent Inflammatory Bowel Disease in a Randomized Trial. Gastroenterology. 2020;158(1):176-188.e7. PMID 31586453
  17. Sood R, Gracie DJ, Law GR, Ford AC. Systematic review with meta-analysis: the accuracy of diagnosing irritable bowel syndrome with symptoms, biomarkers and/or psychological markers. Aliment Pharmacol Ther. 2015;42(5):491-503. PMID 26076071
  18. Villanueva-Millan MJ, et al. Methanogens and Hydrogen Sulfide Producing Bacteria Guide Distinct Gut Microbe Profiles and Irritable Bowel Syndrome Subtypes. Am J Gastroenterol. 2022;117(12):2055-2066. PMID 36114762
  19. Kim G, et al. Methanobrevibacter smithii is the predominant methanogen in patients with constipation-predominant IBS and methane on breath. Dig Dis Sci. 2012;57(12):3213-8. PMID 22573345
  20. Ghoshal U, et al. Irritable Bowel Syndrome, Particularly the Constipation-Predominant Form, Involves an Increase in Methanobrevibacter smithii, Which Is Associated with Higher Methane Production. Gut Liver. 2016;10(6):932-938. PMID 27458176
  21. Villanueva-Millan MJ, et al. Hydrogen Sulfide Producers Drive a Diarrhea-Like Phenotype and a Methane Producer Drives a Constipation-Like Phenotype in Animal Models. Dig Dis Sci. 2024;69(2):426-436. PMID 38060167
  22. Talamantes S, et al. Intestinal Methanogen Overgrowth (IMO) Is Associated with Delayed Small Bowel and Colonic Transit Time on the Wireless Motility Capsule. Dig Dis Sci. 2024;69(9):3361-3368. PMID 39068378
  23. Gottlieb K, Wacher V, Sliman J, Pimentel M. Review article: inhibition of methanogenic archaea by statins as a targeted management strategy for constipation and related disorders. Aliment Pharmacol Ther. 2016;43(2):197-212. PMID 26559904
  24. Muskal SM, et al. Lovastatin lactone may improve irritable bowel syndrome with constipation (IBS-C) by inhibiting enzymes in the archaeal methanogenesis pathway. F1000Res. 2016;5:606. PMID 27347377
  25. Hubert S, et al. Development of a Modified-Release Formulation of Lovastatin Targeted to Intestinal Methanogens Implicated in Irritable Bowel Syndrome With Constipation. J Pharm Sci. 2018;107(2):662-671. PMID 28989013
  26. Luo M, Zhuang X, Tian Z, Xiong L. Alterations in short-chain fatty acids and serotonin in irritable bowel syndrome: a systematic review and meta-analysis. BMC Gastroenterol. 2021;21(1):14. PMID 33407171
  27. Sun Q, et al. Alterations in fecal short-chain fatty acids in patients with irritable bowel syndrome: A systematic review and meta-analysis. Medicine (Baltimore). 2019;98(7):e14513. PMID 30762787
  28. Ju X, et al. Changes in Fecal Short-Chain Fatty Acids in IBS Patients and Effects of Different Interventions: A Systematic Review and Meta-Analysis. Nutrients. 2024;16. PMID 38892659
  29. So D, et al. Effects of a low FODMAP diet on the colonic microbiome in irritable bowel syndrome: a systematic review with meta-analysis. Am J Clin Nutr. 2022;116(4):943-952. PMID 35728042
  30. Ng QX, et al. What Has Longitudinal 'Omics' Studies Taught Us about Irritable Bowel Syndrome? A Systematic Review. Metabolites. 2023;13. PMID 37110143
  31. O'Mahony L, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128(3):541-51. PMID 15765388
  32. Whorwell PJ, et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastroenterol. 2006;101(7):1581-90. PMID 16863564
  33. Yuan F, et al. Efficacy of Bifidobacterium infantis 35624 in patients with irritable bowel syndrome: a meta-analysis. Curr Med Res Opin. 2017;33(7):1191-1197. PMID 28166427
  34. Ringel-Kulka T, et al. Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study to Evaluate the Benefit of the Probiotic Bifidobacterium infantis 35624 in Non-Patients With Symptoms of Abdominal Discomfort and Bloating. Am J Gastroenterol. 2017;112(1):145-151. PMID 27845337
  35. Brenner DM, Moeller MJ, Chey WD, Schoenfeld PS. The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review. Am J Gastroenterol. 2009;104(4):1033-49. PMID 19277023
  36. Charbonneau D, Gibb RD, Quigley EM. Fecal excretion of Bifidobacterium infantis 35624 and changes in fecal microbiota after eight weeks of oral supplementation with encapsulated probiotic. Gut Microbes. 2013;4(3):201-11. PMID 23549409
  37. Burns GL, et al. Serological and faecal markers of irritable bowel syndrome: a systematic review and meta-analysis. EBioMedicine. 2026;126:106198. PMID 41793943
  38. Johnsen PH, et al. Faecal microbiota transplantation in irritable bowel syndrome (REFIT2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2026. PMID 42785338
  39. Liu J, et al. Healthy donor faecal microbiota transplantation in irritable bowel syndrome: interpreting negative findings. Lancet. 2026. PMID 42785337
  40. Hurych J, et al. Protocol for faecal microbiota transplantation in irritable bowel syndrome: the MISCEAT study - a randomised, double-blind cross-over study using mixed microbiota from healthy donors. BMJ Open. 2022;12(6):e056594. PMID 35760542
  41. Cinek O, et al. Faecal microbiota transplantation in patients with irritable bowel syndrome modulates the gut microbiome but lacks clinical effects: results of a randomised, double-blind crossover clinical trial. Research Square. 2026 Oct 23 (preprint, not peer reviewed). doi:10.21203/rs.3.rs-11289849/v1