Fecal-microbiota transplant shows promise for moderate-to-severe IBS

By Will Boggs MD

NEW YORK (Reuters Health) - Fecal-microbiota transplant (FMT) significantly improves symptom scores in patients with moderate-to-severe irritable bowel syndrome (IBS), researchers from Norway report.

"This is still an experimental treatment,” Dr. Peter Holger Johnsen from the University Hospital of North Norway Harstad told Reuters Health by email. “We know too little about what characterizes a healthy donor flora and what IBS subgroup benefits from the treatment. A larger study is also needed to do safety analysis of the short- and long-term effects.”

Alterations in the intestinal microbiota are thought to be part of the pathophysiology of IBS, suggesting FMT as a possible treatment option for restoring normal gut microbiota.

Dr. Johnsen’s team investigated the effectiveness of FMT in a double-blind, randomized controlled trial of 83 patients with moderate-to-severe IBS, as defined by an IBS severity scoring system (IBS-SSS) score of 175 or higher.

The primary endpoint was symptom reduction of more than 75 points assessed by IBS-SSS three months after FMT.

“The primary questionnaire we used to assess the effect of treatment has defined a 50-point reduction as clinically meaningful, while we have used an even more conservative definition of responders with a cutoff at 75 points,” Dr. Johnsen said.

By this criterion, 65% of participants receiving donor FMT showed a response at three months, compared with 43% of participants receiving placebo (FMT using their own feces; P=0.049), the team reports in The Lancet Gastroenterology & Hepatology, online October 31.

By 12 months, response rates did not differ significantly between the active-treatment and placebo groups (56% vs. 36%; P=0.075).

In a post hoc analysis, participants who received frozen FMT had lower symptom scores throughout follow-up, compared with those who received fresh FMT, but after adjustment for other functional comorbidity, both formulations had a similar effect on IBS-SSS scores.

Adverse events were few and transient, including abdominal pain in one active transplant participant and two placebo transplant participants, and nausea and vertigo in one person in the active transplant group.

“It looks like some of the participants relapse in severity at 12 months,” Dr. Johnsen said. “We have now developed an enema technique where the transplant reaches the proximal part of the colon. This mode of delivery should have an effect equal to colonoscopic delivery. By this mode of delivery, relapsers could have repeated treatments to maintain the effect. We have just finished the treatments in an open-labeled extension to the trial where the placebo group is treated with this enema technique. Results will be available in about 6 months.”

“Research in how FMT causes symptom relief in IBS might reveal mechanisms in IBS pathophysiology amenable to other treatments, making FMT unnecessary,” he speculated. “As a related example: It is now shown through research of FMT in toxin-producing Clostridium difficile that spore formation might be caused by a dysbiosis that disturbs the metabolism of primary bile acids. Secondary bile acid metabolites from the microflora are suggested as a possible treatment mechanism for recurrent CDI.”

Dr. Alexander C. Ford from St. James's University Hospital, in Leeds, UK, who wrote an accompanying editorial, told Reuters Health by email, “A single FMT may be beneficial in the short term, but larger studies are needed and we need to know if repeat FMT produces a durable improvement in symptoms.”

He envisions FMT being used "after failure of most other medical therapies, as things stand."

Dr. Olga C. Aroniadis from Montefiore Medical Center, in New York City, who has published extensively on FMT and its possible uses, told Reuters Health by email, "This is an exciting study that was conducted with scientific rigor and precision. The results suggest that FMT may be an appropriate and effective treatment option for specific groups of patients with IBS. Further clinical trials are needed to support or refute these results.”

“Our understanding of the risks of FMT is evolving, and until we have long-term safety data for FMT, I envision that FMT would be used to manage IBS patients in whom conservative therapy has failed,” she said. “FMT may be most efficacious in patients who have post-infection IBS, a chronic disorder that ensues following a bout of acute gastroenteritis. IBS patients with additional functional comorbidities and excessive somatic symptoms may be less likely to respond to FMT, because the etiology of IBS symptoms among such patients may have a psychological basis.”

“We have just completed a clinical trial assessing the role of FMT administered via oral capsules to patients with diarrhea-predominant IBS and very soon hope to add to this current exciting and groundbreaking study,” Dr. Aroniadis said.

Dr. Andreas Munk Petersen from the University of Copenhagen and Hvidovre Hospital, in Denmark, concluded in a recent systematic review that data on FMT for IBS are too limited to draw meaningful conclusions. He told Reuters Health by email, "In this study, they did not report if patients had their microbiota changed by their FMT procedure, since they did not perform any microbiota analysis, either before or after the FMT procedure. This weakens the results considerably.”

“More studies are needed before FMT should be used in the general IBS population,” he concluded.

SOURCES: http://bit.ly/2yzkG81 and http://bit.ly/2zIt1Yx

Lancet Gastroenterol Hepatol 2017.

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