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Overview — irritable bowel syndrome

TL;DR — IBS is a disorder of gut–brain interaction defined by a symptom rule applied after limited investigation finds no organic explanation, and every quantitative claim about it inherits that definition. Measured prevalence is 9.2% (95% CI 7.6–10.8) under Rome III and 3.8% (3.1–4.5) under Rome IV in the same meta-analysis (Oka 2020, PMID 32702295); Rome V, published May 2026, returns 8.5% globally (Sperber 2026, PMID 42613194) while identifying a partly different group of people (κ 0.36–0.55 versus its predecessors; Staller 2026, PMID 42392123). Three decades of mechanistic work have produced a long list of reproducible peripheral and central abnormalities and no validated diagnostic biomarker; only three mechanisms are quantifiable with validated tests — bile acid metabolism, colonic transit and psychological comorbidity (Nasser 2026, PMID 42462748). In two head-to-head diet-versus-drug trials, dietary therapy beat optimised drug treatment in a specialist clinic (76%/71% vs 58% responders; Nybacka 2024, PMID 38643782) and a smartphone FODMAP app beat an antispasmodic in primary care (71% vs 61%; Carbone 2022, PMID 35483886). Well-supported non-dietary options include low-dose amitriptyline in primary care (Ford 2023, PMID 37858323) and brain–gut behavioural treatments, whose estimates cannot be ranked directly against the drug because no head-to-head trial exists (Everitt 2019, PMID 30971419; Thakur 2025, PMID 41077057). Placebo response is 27.3–37.5% depending on endpoint (Bosman 2021, PMID 33765447; Ford 2010, PMID 20412064), open-label placebo did not differ significantly from blinded placebo in one trial (Lembo 2021, PMID 33605656), and mean generic quality of life in one UK Rome IV cohort was comparable to published values for stroke or COPD (Goodoory 2023, PMID 36544055). The single most useful habit when reading this literature is to ask which criteria defined the population.

What IBS is

A criteria-defined syndrome of recurrent abdominal pain associated with defecation or with a change in stool frequency or form, in the absence of organic disease after limited investigation. The current framing is disorder of gut–brain interaction (DGBI), replacing "functional gastrointestinal disorder", introduced at Rome IV and retained at Rome V (Drossman 2016, PMID 27144617; Drossman 2026, PMID 42031435). The Rome V process defines DGBI by "any combination of motility disturbance, visceral hypersensitivity, altered mucosal and immune function, altered gut microbiota, or altered central nervous system processing" (Drossman 2026, PMID 42031435).

Three properties follow from being criteria-defined, and they organise this whole knowledge base:

  1. The denominator moves with the rule. Rome III → Rome IV halved community prevalence, almost entirely because the minimum pain frequency rose from 2–3 days/month to ≥1 day/week (Palsson 2020, PMID 31917991).
  2. Subtypes are unstable. Stool-form subtyping is the most stable classification available and is only κ 0.60 stable over 12 months; only 73.6% of patients still met Rome IV criteria at all (Khasawneh 2026, PMID 41447016).
  3. The categories may not be discrete. Latent-class analysis of the non-IBS functional bowel disorders concluded they "may be better characterised as a spectrum of IBS rather than separate disorders" (Black 2022, PMID 35531932).

The numbers that matter

Question Answer Source
Prevalence, Rome III 9.2% (7.6–10.8) Oka 2020, PMID 32702295
Prevalence, Rome IV 3.8% (3.1–4.5) Oka 2020, PMID 32702295
Prevalence, Rome V (15 countries, 28,771 adults) 8.5% Sperber 2026, PMID 42613194
Sex ratio OR 1.46 (1.33–1.59) for women Oka 2020, PMID 32702295
Generic quality of life (EQ-5D) 0.570 (SD 0.283), comparable to stroke, leg ulcers, COPD Goodoory 2023, PMID 36544055
Work impairment 85.6% presenteeism, 28.5% absenteeism; 72–188 million UK hours/year Goodoory 2022, PMID 35794733
Direct cost per patient/year US$193 (Korea) to US$31,113 (US, IBS-C), 2024 dollars Neo 2026, PMID 42538760
Post-infectious incidence 14.5% after acute gastroenteritis; OR 4.3 vs unexposed Porcari 2024, PMID 39013599
Overlap with functional dyspepsia 34.6% (28.2–41.4) pooled; 55.3% in a Rome IV cohort Andreev 2022, PMID 36286762; Barberio 2022, PMID 33839276
Placebo response (global improvement) 27.3% (24.3–30.9); 37.5% (34.4–40.6) in an earlier pool Bosman 2021, PMID 33765447; Ford 2010, PMID 20412064
Rectal hypersensitivity at optimal barostat cut-off 63.5% of patients, 6.6% of controls Ludidi 2012, PMID 22591192
Genetic correlation with anxiety/neuroticism/depression rg > 0.5 Eijsbouts 2021, PMID 34741163

What works, ranked by the evidence that exists

Intervention Best evidence Effect
Dietary therapy CARIBS RCT (Nybacka 2024, PMID 38643782); DOMINO RCT (Carbone 2022, PMID 35483886); NMA of 28 trials (Cuffe 2025, PMID 40258374) Beat optimised drugs (76%/71% vs 58%) and beat an antispasmodic in primary care (71% vs 61%); low FODMAP RR of global symptoms not improving 0.51 (0.37–0.70) vs habitual diet
Brain–gut behavioural therapy ACTIB RCT (Everitt 2019, PMID 30971419); NMA of 67 trials (Thakur 2025, PMID 41077057) IBS-SSS −61.6 (telephone CBT) and −35.2 (web CBT) vs usual care at 12 months; hypnotherapy 61.8% responders at 2 years (Lövdahl 2025, PMID 40491242). No trial at low risk of bias across all domains
Gut–brain neuromodulators ATLANTIS RCT (Ford 2023, PMID 37858323); NMA of 28 trials (Khasawneh 2025, PMID 40258375) IBS-SSS −27.0 (−46.9 to −7.10); tricyclics RR of global symptoms not improving 0.70 (0.62–0.80), moderate certainty
Secretagogues (IBS-C) 15-trial NMA (Black 2018, PMID 30144426); AGA guideline (Chang 2022, PMID 35738724) Linaclotide 33.7% vs 13.9% responders (NNT 5.1); the only strong recommendation in any IBS guideline
Rifaximin (non-constipated IBS) TARGET 1/2 (Pimentel 2011, PMID 21208106); TARGET 3 (Lembo 2016, PMID 27528177) 40.7% vs 31.7% adequate relief; safest IBS drug measured
5-HT3 antagonists (IBS-D) 21-trial NMA (Rokkas 2021, PMID 34276193); ramosetron RCT (Fukudo 2016, PMID 26551550) Ramosetron 50.7% vs 32.0% global improvement (NNT 6); class risk is ischaemic colitis
Peppermint oil / antispasmodics 51-trial NMA (Black 2020, PMID 31859183); Ingrosso 2022, PMID 35942669 Peppermint oil ranked first for global symptoms (RR 0.63, 0.48–0.83) but failed both co-primary endpoints in its best single trial (Weerts 2020, PMID 31470006)
Eluxadoline (IBS-D) Two phase 3 trials (Lembo 2016, PMID 26789872) 23.9–29.6% vs 16.2–17.1%; pancreatitis and sphincter-of-Oddi spasm limit use
Probiotics 82-trial meta-analysis (Goodoory 2023, PMID 37541528) Strain-specific; low to very low certainty across almost every analysis
FMT Contradictory trials (El-Salhy 2020, PMID 31852769 vs Lahtinen 2020, PMID 32343000 and Yau 2023, PMID 37667968) Unresolved; meta-analyses disagree on whether an effect exists

Map of the condition

Foundations - diagnosis-and-rome-criteria — Manning 1978 to Rome V 2026; what each rewrite did to the denominator; subtyping and its instability. - epidemiology-and-burden — prevalence by criteria and region, sex and age, incidence and remission, cost.

Diagnosis - differential-diagnosis-and-exclusion — coeliac, IBD, microscopic colitis, bile acid diarrhoea; test yields and miss rates.

Mechanism - brain-gut-axis-and-visceral-hypersensitivity — the mechanistic map, hypersensitivity, genetics, bidirectionality. - microbiome — the largest sub-literature with the least clinical yield. - post-infectious-ibs — the one route in with a datable start and a validated risk score.

Treatment - dietary-therapy — low FODMAP, comparative trials, fibre, restriction costs. - antispasmodics-and-peppermint — old drugs, weak trials, and a randomised experiment on labelling. - constipation-predominant-pharmacotherapy — secretagogues, tegaserod's regulatory arc. - diarrhoea-predominant-pharmacotherapy — eluxadoline, 5-HT3 antagonists, and the field's real drug harms. - rifaximin-and-the-sibo-question — an antibiotic that works and a construct that may not exist. - gut-brain-neuromodulators — ATLANTIS and the class evidence. - psychological-therapy — the largest effects and the worst access.

Method - placebo-response-and-trial-design — magnitude, components, open-label placebo, endpoint engineering.

Clinical - overlap-with-functional-dyspepsia — scoped as overlap, not as a separate condition. - guidelines — where societies agree and where they don't. - clinical-trials-landscape — 1,171 registered studies, live counts from 2026-09-02.

Human - quality-of-life-and-stigma — burden, work impairment, measured stigma, invalidation. - red-flags-and-safety-concerns — alarm features, drug harms, dietary harms, suicidality.

Four things that are true and uncomfortable

  1. The best-supported first-line treatment is a diet, and the trials that show it were investigator-led. CARIBS and DOMINO both beat drugs; neither was industry-funded (Nybacka 2024, PMID 38643782; Carbone 2022, PMID 35483886).
  2. Telling patients a pill is a placebo does not stop it working. Open-label placebo beat no-pill control and did not differ significantly from double-blind placebo (d=0.10) (Lembo 2021, PMID 33605656); and in a 2×2 factorial trial the label "mebeverine" nearly doubled response while the drug itself did nothing (Rexwinkel 2025, PMID 40074185).
  3. Stigma is measurable and specific to this diagnosis. Randomised vignettes produced higher enacted stigma toward IBS than toward inflammatory bowel disease or asthma (Taft 2017, PMID 27501483); 38% of tertiary-care patients had contemplated suicide because of their bowel symptoms (Miller 2004, PMID 15625650).
  4. The mechanistic literature is enormous and clinically inert. 2,797 PubMed records for irritable bowel syndrome AND (microbiome OR microbiota) on 2026-09-02, no validated microbiome test; eleven candidate biomarkers "performed no better than symptom-based criteria" (Sood 2015, PMID 26076071).

Open questions

The full tiered set is in OPEN-QUESTIONS.md. The four that most constrain everything else:

  • Are treatment effects criteria-dependent? Rome III, IV and V select different people; targeted PubMed and ClinicalTrials.gov searches on 2026-09-02 retrieved no within-population trial stratified by criteria set (Staller 2026, PMID 42392123).
  • Neuromodulator or behavioural therapy first in primary care? Both work; targeted PubMed and registry searches on 2026-09-02 retrieved no head-to-head trial (Ford 2023, PMID 37858323; Everitt 2019, PMID 30971419).
  • Is dysbiosis cause or consequence? Posed in 2019 and unanswered (Pittayanon 2019, PMID 30940523).
  • What is the placebo response made of, and can any trial design separate it from drug effect (Kaptchuk 2008, PMID 18390493; Bosman 2021, PMID 33765447)?

All twenty pages are listed in the map above. Start with diagnosis-and-rome-criteria if you want to understand why every other number on this page carries a qualifier.

References

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  2. Sperber AD, et al. Rome V global epidemiology and validation survey. Gut. 2026 Aug 18 (online ahead of print). PMID 42613194
  3. Staller K, et al. The Rome V criteria for the diagnosis of irritable bowel syndrome in secondary care: a diagnostic accuracy study. Lancet Gastroenterol Hepatol. 2026;11(9):812-820. PMID 42392123
  4. Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016. PMID 27144617
  5. Drossman DA, Chang L, Tack J. Disorders of Gut-Brain Interaction and the Rome V Process. Gastroenterology. 2026;170(6):1083-1098. PMID 42031435
  6. Palsson OS, Whitehead W, Törnblom H, Sperber AD, Simren M. Prevalence of Rome IV Functional Bowel Disorders Among Adults in the United States, Canada, and the United Kingdom. Gastroenterology. 2020;158(5):1262-1273.e3. PMID 31917991
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  8. Black CJ, Houghton LA, Ford AC. Latent class analysis does not support the existence of Rome IV functional bowel disorders as discrete entities. Neurogastroenterol Motil. 2022;34(11):e14391. PMID 35531932
  9. Nasser Y, Shin A, Ford AC, Camilleri M, Black CJ. Pathophysiology of irritable bowel syndrome. Lancet Gastroenterol Hepatol. 2026 Jul 16 (online ahead of print). PMID 42462748
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  25. Ingrosso MR, et al. Systematic review and meta-analysis: efficacy of peppermint oil in irritable bowel syndrome. Aliment Pharmacol Ther. 2022;56(6):932-941. PMID 35942669
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