New evidence from a cumulative RCT analysis suggests irritable bowel syndrome patients do not definitively benefit from FMT treatment.
Chung Owyang, MD
New research shows that about half of all irritable bowel syndrome (IBS) patients treated with fecal microbiota transplantation (FMT) exhibited clinical improvements. That said, the cumulative study findings were not consistent to a definitive conclusion.
A team led by Chung Owyang, MD, chief of the Division of Gastroenterology and Hepatology at the University of Michigan, discovered short-term global improvements of IBS symptoms between 8-12 weeks after FMT, the recommended duration for the assessment of short-term responses to therapy in functional gastrointestinal (GI) disorders.
However, the investigators saw no substantial difference in the global improvement of symptoms in the 152 patients treated with FMT after 12 weeks compared to the 102 patients who received placebo.
The investigators performed a systematic literature search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science and scored the RCTs against the results of a placebo using FMT excipients or autologous FMT in IBS.
To be included in the study, the placebo-controlled trials were prospective, randomized, double-blind, with IBS patients as defined by accepted symptom-based criteria, and older than 16 years old. Each study carried a primary outcome of improvement in global IBS symptoms with a minimum of an 8-week follow-up, and compared treatment to a placebo consisting of only the FMT excipients or an autologous FMT.
Overall, the Michigan investigators researched 742 citations and narrowed down 4 citations involving 254 participants that met eligibility.
All the studies reviewed used the Rome III criteria to diagnose IBS. One of the studies included only IBS-D, while 2 studies included IBS without constipation, and 1 study included all 3 subtypes of IBS.
FMT was administered using a colonoscopy in 1 study, while oral capsules were used in 2 studies and nasojejunal tubes were used in 1 study.
The pair of non-oral studies performed single-dose administration of donor or autologous fecal microbiota preparation, while the 2 oral capsules FMT studies used multiple doses—between 3-12—of donor microbiota or placebo consisting of FMT excipients alone without microbiota.
A further analysis revealed that a single-dose of FMT using colonoscopy and nasojejunal tubes was more beneficial than using autologous FMT for placebo treatment.
The colonoscopy and nasojejunal tube treatment also reduced the likelihood of improvement of multiple-dose capsule FMT in the randomized controlled trials (RCTs).
The placebo response was 33.7% in nonoral FMT RCTs and 67.8% in capsule FMT RCTs.
In 1 of the studies, investigators found an increase in richness and a shift of recipients’ microbial community composition toward donors’ microbial communities that was maintained up to 6 weeks after treatment. However, the changes were not associated with clinical responses to therapy.
Another of the studies showed no microbial composition differences, while a different study demonstrated significant differences in post-FMT fecal microbiota between successful active treatment and unsuccessful placebo treatment.
“Using the endpoint of global improvement in IBS symptoms at 12 weeks after FMT, 4 RCTs involving 254 participants for evaluation of FMT in IBS have yielded statistically inconclusive results, with no significant difference in global improvement between FMT and placebo, and significant inconsistency of results,” investigators wrote.
FMT targets gut dysbiosis, and has been proven an effective treatment forClostridium difficile infection.
“Current evidence from RCTs does not suggest a benefit of FMT for global IBS symptoms,” investigators wrote. “There remain questions regarding the efficacy of FMT in IBS as well as the lack of a clean explanation on the discrepant results among RCTs in subgroup analyses.”
IBS is widely considered to be the most commonly diagnosed gastrointestinal condition, impacting between 5.8% and 17.5% of the population worldwide. The symptoms often range in severity and can overlap with other functional disorders and psychiatric conditions.
In recent years, investigators have identified a disturbance of the gut microbiota in IBS patients that includes decreased diversity when compared to healthy patients. One possible treatment option, supported by a plethora of evidence from clinical trials using antibiotics, probiotics and dietary modifications, is manipulating the gut microbiota.
The study, “Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome,” was published online in The American Journal of Gastroenterology.