Summary

First-ever ACG GRADE-based clinical guideline on IBS management addressing 25 PICO questions (9 diagnostic, 16 therapeutic). Endorses positive symptom-based diagnosis over diagnosis of exclusion, with targeted serologic and fecal testing to rule out celiac disease and IBD in IBS-D. Recommends low-FODMAP diet, soluble fiber, secretagogues (linaclotide, plecanatide, lubiprostone, tegaserod) for IBS-C; rifaximin, alosetron, eluxadoline for IBS-D; TCAs and gut-directed psychotherapy across subtypes. Recommends against routine food allergy testing, PEG monotherapy for global IBS-C symptoms, and FMT.

Key Recommendations

Use a positive diagnostic strategy (Rome IV symptom criteria + limited workup) rather than diagnosis of exclusion to shorten time to therapy.
Check serologic testing (IgA tTG + quantitative IgA) to rule out celiac disease in patients with IBS-D.
Check fecal calprotectin (or fecal lactoferrin) plus CRP to rule out IBD in patients with suspected IBS-D.
Do not routinely test for enteric pathogens including Giardia unless risk factors are present (travel, daycare, camping, endemic exposure).
Do not perform routine colonoscopy in IBS patients <45 years without alarm features; consider in women >60 with diarrhea to evaluate microscopic colitis.
Recommend a limited trial of low-FODMAP diet (3-phase: restriction, reintroduction, personalization) ideally guided by a GI dietitian.
Use soluble, viscous, poorly fermentable fiber (psyllium/ispaghula) rather than insoluble bran for IBS symptoms.
Recommend chloride channel activator (lubiprostone) and guanylate cyclase-C agonists (linaclotide, plecanatide) for global IBS-C symptoms; tegaserod for women <65 with ≤1 CV risk factor.
Recommend against PEG alone for global IBS-C symptoms (improves constipation but not abdominal pain).
Recommend rifaximin for IBS-D; retreatment is safe and effective for symptom recurrence.
Use alosetron in women with severe refractory IBS-D; use eluxadoline for IBS-D (contraindicated post-cholecystectomy, pancreatitis, heavy alcohol use).
Use TCAs (not SSRIs) for global IBS symptoms, starting low (e.g., amitriptyline 10 mg) and titrating up.
Offer gut-directed psychotherapy (CBT or gut-directed hypnotherapy) as adjunct for IBS across subtypes.
Do not perform routine food allergy testing or IgG food panels in IBS patients.
Do not use fecal microbiota transplantation for IBS outside of trials.

Thresholds & Doses

Rome IV: abdominal pain ≥1×/week on average associated with defecation, change in stool frequency, or stool form.
Celiac screen yield highest in IBS-D (EMA/tTG ~5.7% prevalence); duodenal biopsy: ≥6 specimens including bulb if endoscopy performed.
Fecal calprotectin for IBD: sensitivity 93%, specificity 96%; CRP ≤0.5 mg/dL yields ~1% probability of IBD.
Colonoscopy not indicated for IBS <45 years without alarm features.
Total fiber intake target: 25–35 g/day; psyllium NNT ≈ 7 for IBS symptom improvement.
Lubiprostone: 8 μg PO BID with meals for women with IBS-C (NNT 12.5).
Linaclotide: 290 μg PO daily for IBS-C (NNT 6).
Plecanatide: 3 mg PO daily for IBS-C (NNT ~10).
Tegaserod: 6 mg PO BID for women <65 with IBS-C and ≤1 CV risk factor; contraindicated with >1 CV risk factor or prior ischemic event.
Rifaximin: 550 mg PO TID × 2 weeks for IBS-D; up to 2 retreatments allowed; NNT 9; NNH 8,971.
Alosetron: 0.5–1 mg PO BID for women with severe chronic (>6 months) refractory IBS-D under REMS; NNT 7.5; NNH 10.
Eluxadoline: 100 mg PO BID (75 mg BID if no gallbladder/hepatic impairment); contraindicated without gallbladder, pancreatitis history, or >3 alcoholic drinks/day.
TCA starting dose: amitriptyline or desipramine 10 mg, titrate up; NNT 4.5; NNH 9–18.
Peppermint oil: NNT 3 for global symptoms, NNT 4 for abdominal pain.
Postinfection IBS pooled prevalence ~11%; 41.9% after parasitic vs 13.8% after bacterial enteritis.

Citations

Rome IV diagnostic criteria (Table 1) — IBS definition and symptom-based diagnosis
Recommendation on celiac screening — IgA tTG in IBS-D
Recommendation on fecal calprotectin/CRP — IBD exclusion in IBS-D
Recommendation on colonoscopy — alarm features and age thresholds
Recommendation on low-FODMAP diet — 3-phase approach with dietitian guidance
Recommendation on fiber — soluble (psyllium) over insoluble bran
Recommendations on IBS-C secretagogues — lubiprostone, linaclotide, plecanatide, tegaserod doses and NNTs
Recommendation on rifaximin, alosetron, eluxadoline — IBS-D therapeutics and safety
Recommendation on TCAs and gut-directed psychotherapy — global symptom management
Table 2 — Summary and strength of recommendations