Largest IBS faecal transplant trial (REFIT2) finds no benefit over placebo enema

Results from REFIT2 (Recalibrating the Intestinal Microbiota by Fecal Microbiota Transplantation 2), a phase 3, double-blind, placebo-controlled trial of faecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS), were highlighted on 27 October 2026 in Nature Reviews Gastroenterology & Hepatology after publication in The Lancet. The Norwegian study enrolled 450 adults (18–65 years; about 65% women) with moderate-to-severe IBS (Rome IV; IBS-SSS ≥175) across five hospitals.

Design and primary result

• Randomisation 2:1 to a once-only rectal enema of donor stool (n=299) or the participant’s own stool as placebo (n=151); investigators and participants were blinded. Three donors were used.
• Primary endpoint: ≥75-point improvement on the IBS Symptom Severity Score at 90 days — met by 40% on donor FMT vs 38% on placebo (absolute difference 1.9 percentage points; 95% CI −8.1 to 12.0; p=0.76).
• At one year, rates were 44% vs 45%. No clear gains on quality of life, global relief, pain, or subtype-specific stool measures. Microbiota nonetheless shifted toward donor profiles, showing engraftment without clinical benefit.

Safety and limitations

Adverse events were similar overall (24 in the FMT arm including six serious, vs eight with none serious in placebo); four and three participants respectively had events potentially related to FMT. Limitations include a single delivery route (enema, not colonoscopy), use of three donors (inter-donor variation may dilute effects), and no standardised dietary co-intervention — points raised in accompanying commentary that still argue for targeted microbiome therapies rather than discarding the microbiome idea. This was a large randomised trial, but one protocol; talk to your doctor before considering any microbiome therapy for IBS.