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Fecal Microbiota Transplantation: Moving Mainstream, Regulatory Hurdles and Potential Future Indications

Published reports of fecal microbiota transplantation in modern history date as far back as the 1950s, but in just the past few years, it has rapidly moved from the fringe toward the mainstream as a highly effective therapy for recurrent Clostridium difficile infection. Mounting data have established fecal microbiota transplantation’s efficacy and apparent safety for this indication, and as the incidence of C. difficile infection continues to increase along with more recurrent, severe and antibiotic-resistant cases, fecal microbiota transplantation has thus become an increasingly accepted intervention by patients, physicians, researchers, industry and regulatory bodies.

While experts agree fecal microbiota transplantation (FMT) appears safe and is relatively simple to perform, a number of challenges continue to limit more widespread practice; these include evolving regulatory issues and the need for more prospective safety data, best practices and improved delivery methods. Furthermore, as FMT’s high cure rate for recurrent C. difficile infection is essentially a proof-of-concept for treating disease by altering the intestinal microbiome, a boom in research on FMT for other indications is currently ongoing, and refined therapeutic alternatives to whole stool transplantation are in development.

Healio Gastroenterology spoke to several experts who recently presented data on FMT at Digestive Disease Week 2015 in Washington, D.C., all of whom agreed that there is still much work to be done to refine FMT and better understand the underlying mechanisms and broader implications of microbiome-based therapies.

A Mainstay for Recurrent C. difficile, Promising for Severe C. difficile

In the past few years, multiple systematic reviews and meta-analyses have been published showing FMT has approximately 90% efficacy in treating recurrent C. difficile infection with minimal adverse events. The most recent by Drekonja and colleagues, which looked at two randomized controlled trials and 21-case series involving 516 patients who received FMT for recurrent C. difficile infection, demonstrated symptom resolution in 85% of patients across all studies.

“We have a large number of papers and great quality of data supporting great efficacy and safety of fecal transplant in the treatment of recurrent C. diff,” Monika Fischer, MD, MSc, from Indiana University Health, said during her presentation at DDW. In addition to the systematic reviews and meta-analyses, “now we have three [randomized controlled trials] evaluating this question,” the findings of which she summarized during her talk.

Monika Fischer, MD, MSc

Monika Fischer

In the first study by van Nood and colleagues, published in 2013 in the New England Journal of Medicine, a total of 43 patients were randomly assigned to receive FMT via nasoduodenal tube following an abbreviated vancomycin regimen and bowel lavage, a standard vancomycin regimen or a standard vancomycin regimen with bowel lavage. “This study … was terminated early because of the interim analysis discovering superior results in the fecal transplant compared to the vancomycin group,” Fischer said.

The next, published by Youngster and colleagues, in 2014 in Clinical Infectious Diseases, “evaluated the differences between colonoscopy and nasogastric tube delivery mode. They used frozen stool and they found slightly better outcomes in the colonoscopy delivery. … Overall they showed a similarly high cure rate of 90% and notably no adverse events were reported.”