Fecal Transplants Effective for Some With Inflammatory Bowel Disease

By Will Boggs MD

May 25, 2017

NEW YORK (Reuters Health) - Fecal microbiota transplantation (FMT) might prove effective for some patients with inflammatory bowel disease, especially those with ulcerative colitis (UC), according to a systematic review.

"While there is enormous interest in the potential role of FMT as a treatment for inflammatory bowel diseases and the randomized controlled trial data in UC is encouraging, there still remains insufficient evidence to recommend it as part of standard clinical care,” said Dr. Natalia Castano-Rodriguez from The University of New South Wales in Sydney, Australia.

“Further studies are needed to better identify clinical and microbial predictors of response, optimize treatment protocol, and characterize (long-term) sequelae,” she told Reuters Health by email.

FMT is extremely effective in the treatment of Clostridium difficile infection and is thought to have potential in other conditions where there are imbalances in the enteric microbiota, such as the inflammatory bowel diseases (IBD).

Dr. Castano-Rodriguez's team summarize the available literature and evaluate the efficacy of FMT in UC, Crohn's disease (CD) and pouchitis in their systematic review of 53 articles.

In a pooled analysis of 24 cohort studies, 33% of patients with UC achieved clinical remission and 52% achieved clinical responses, with a moderate risk of heterogeneity, the researchers report in the Journal of Crohn's and Colitis, online May 9.

Meta-analysis of four randomized controlled trials indicated that FMT led to a significant 2.89-fold increase in the odds of clinical remission. There was also a significant 2.48-fold increase in the odds of clinical response in UC patients.

Based on 11 studies, 52% of CD patients achieved clinical remission and 63% achieved clinical responses, with a moderate risk of heterogeneity.

Only four studies assessed FMT in pouchitis: no patients achieved clinical remission, two of eight achieved clinical response, and five of seven had global symptom improvement. In a single study that allowed for multiple FMT infusions, four of five patients achieved clinical remission.

Results were mixed for endoscopic outcomes after FMT.

“While microbiota data available from 24 individual studies included in our meta-analysis clearly indicate that there is increased diversity and a shift in recipient microbiota profile towards the donor post-FMT, no consensus has been reached regarding which microbial taxa and/or associated metabolites are directly responsible for remission in IBD patients,” Dr. Castano-Rodriguez said.

“There is need for further well-designed randomized controlled trials that include 16S rRNA gene and transcript sequencing as well as metagenomics and metabolomics to improve our understanding of the underlying mechanisms of FMT as an effective treatment in IBD,” she added.

Few studies reported major adverse events or serious adverse events that were deemed clinically related to FMT therapy.

“Therapeutic microbial manipulation as a treatment option in IBD holds great promise,” Dr. Castano-Rodriguez concluded. “Within this field, over time it is likely that FMT will serve as a stepping stone towards more rationally designed and well-defined microbial consortia therapies that will be informed by an improved appreciation of the underlying microbial and metabolic factors driving the disease process and therapeutic response with FMT.”

Dr. Nitsan Maharshak, head of the IBD Center and Bacteriotherapy Clinic at Tel Aviv Sourasky Medical Center in Israel, told Reuters Health by email, “The meta-analysis strengthens the concept that the enteric microbiome is important for the pathogenesis of inflammatory bowel disease. Multiple studies from all over the world using various FMT techniques have now demonstrated the efficacy of this procedure for IBD - both for ulcerative colitis and Crohn's disease. Despite the fact that some of the trials were not of high quality and clinical remission rate was not very high, this is a complete shift of paradigm.”

“The current study demonstrates the proof-of-concept for the efficacy of this therapy, and we will soon encounter newer, more sophisticated and targeted therapies that will manipulate the enteric microbiome in IBD patients that will probably be safer, cheaper and more efficient than our current arsenal,” said Dr. Maharshak, who was not involved in the review.

“However, currently, FMT for IBD patients should be performed only under supervision and as part of formal clinical trials, given that if the donor is not screened appropriately, significant side effects can occur,” he added.

SOURCE: http://bit.ly/2q8UYmG

J Crohns Colitis 2017.