A randomized trial found that fecal microbiota transplantation (FMT) may be an effective treatment for moderate to severe irritable bowel syndrome (IBS). Researchers in Norway randomly assigned 165 participants to placebo treatment with their own feces, 30 g of FMT, or 60 g of FMT. The primary outcome was a reduction in IBS symptoms, defined as a decrease of at least 50 points in total IBS symptom score. At three months, 23.6% of patients who received placebo, 76.9% of those in the 30-g FMT group, and 89.1% of those in the 60-g FMT group achieved the primary outcome.
The study was published Dec. 18, 2019, by Gut and was summarized in the December 2019, ACP Gastroenterology Monthly. The following commentary, by Nicholas J. Talley, MD, PhD, FACP, and Mudar Irani, MD, appeared in the ACP Journal Club section of the May 19 Annals of Internal Medicine.
FMT is an established therapeutic option for recurrent Clostridioides difficile infection and may be promising for ulcerative colitis, but its role in IBS is controversial. A meta-analysis concluded no overall benefit of FMT, and there seems to be no single, consistent colonic microbial signature in IBS. The randomized trial by El-Salhy and colleagues was high quality and provides more compelling evidence of efficacy in moderate-to-severe IBS. Applying the regulatory European Medicines Agency/US Food and Drug Administration (FDA) composite end point 3 months after FMT, 71% of patients responded to high-dose FMT, 50% to low-dose FMT, and 17% to placebo, with a number needed to treat (NNT) of 2 for the high-dose group and 3 for the low-dose group vs placebo, which was substantially better than the NNT for FDA-approved therapies.
An advantage of successful FMT is that fecal transfer delivered via upper endoscopy seems to be efficacious in all IBS subtypes, unlike other FDA-approved therapies targeting diarrhea or constipation. However, 3 months of follow-up after FMT is insufficient to understand whether benefits are sustained. Meta-analysis data suggest the route of administration is critical: Oral FMT capsules may not be efficacious in IBS. Donor choice is also crucial. With only a single superdonor, the findings of El-Salhy and colleagues may not be generalizable, and dysbiosis did not predict response. Consistent with the concept that there may be an unknown microbial pathogenesis for IBS, the nonabsorbable antibiotic rifaximin is efficacious in diarrhea-predominant and mixed IBS (NNT 9).
Although FMT seems safe in the short term, long-term risks for disease transmission, possibly related to the intestinal microbiome (e.g., Parkinson disease), are uncertain despite rigorous donor screening. Young adult donors may not manifest a transmissible disease until long after donating.