Faecal microbiota transplantation in irritable bowel syndrome (REFIT2): a randomised, double-blind, placebo-controlled, phase 3 trial.

Diagnosis: use a positive diagnostic strategy based on Rome IV criteria rather than a strategy of exclusion (strong for cost-effectiveness, high quality; consensus for time-to-therapy), and categorize by IBS subtype (consensus). In patients with IBS and diarrhea symptoms: check celiac serology (strong, moderate) and, in those WITHOUT alarm features, fecal calprotectin (or fecal lactoferrin) plus CRP to rule out IBD (strong; moderate quality for CRP/calprotectin, very low for lactoferrin). Recommend AGAINST routine stool testing for enteric pathogens (conditional, low) and AGAINST routine colonoscopy in patients younger than 45 without warning signs (conditional, low). Anorectal physiology testing only when symptoms suggest a pelvic floor disorder and/or for refractory constipation not responding to standard medical therapy (consensus). Treatment, all subtypes: soluble, not insoluble, fiber (strong, moderate); a LIMITED trial of a low-FODMAP diet (conditional, very low); gut-directed psychotherapies for global symptoms (conditional, very low); TCAs for global symptoms (strong, moderate); peppermint suggested (conditional, low); antispasmodics for abdominal pain (conditional, low); AGAINST probiotics (conditional, very low), AGAINST fecal transplant (strong, very low). IBS-C: chloride channel activators (strong, moderate) and guanylate cyclase activators (strong, high); AGAINST PEG products for global IBS-C symptoms (conditional, low); tegaserod reserved for women younger than 65 with ≤1 cardiovascular risk factor who have not adequately responded to secretagogues (strong/conditional, low). IBS-D: rifaximin (strong, moderate); alosetron only for women with severe IBS-D who have failed conventional therapy (conditional, low); mixed opioid agonists/antagonists, i.e. eluxadoline (conditional, moderate); AGAINST bile acid sequestrants (conditional, very low).