Fecal microbiota transplant (FMT) has drawn intense interest as a way to treat disease, by adjusting our microbial makeup to harbor more “good” and fewer “bad” bacteria. Based on successful treatment of Clostridium difficile infections, FMT is now being looked at for a wide range of conditions.
The microbiome is thought to influence not only GI infection and disease, but also cancer, neurologic diseases, autism, obesity, metabolic diseases, psychiatric diseases, respiratory diseases and atherosclerosis. More than 200 FMT studies are currently registered on ClinicalTrials.gov, including several dozen pediatric studies.
What is FMT?
FMT delivers an entire microbial community from a healthy individual to an individual with disease. Treatment can be delivered by nasogastric tube, via an endoscopy or colonoscopy, rectally, or, increasingly, in capsule form (one dose is 30 capsules). The FDA still considers FMT an investigational or experimental therapy, classified as both a biologic and a drug.
Fecal microbiota can be transplanted “whole” – in the form of raw stool, fresh or frozen – or it can be purified, modified, extracted and even created synthetically from selected bacterial strains. Stool banks extensively screen their donors and the donations themselves; only about 3 percent of prospective donors are accepted.
FMT isn’t a new concept. The first fecal transplant in modern times was performed in 1958 in four patients with pseudomembranous colitis, in the form of an enema. But the practice dates at least as far back as fourth century China, where “yellow dragon soup” was used to treat cases of severe diarrhea from food poisoning.
FMT’s track record in C. diff
The first large-scale experience with FMT was with recurrent C. difficile (C. diff) infections. C. diff is a leading cause of hospital-associated GI illness and an emerging cause of community cases. It is increasingly antibiotic-resistant, and in the United States in 2011 alone, C. diff was responsible for 29,000 deaths in adults.
Current recommendations are to consider FMT if the patient has a third recurrence of the infection. The first child with recurrent C. diff was treated with FMT in 2010. The first randomized, controlled trial in adults, published in The New England Journal of Medicine, found FMT to be superior to antibiotics (vancomycin) with or without bowel lavage. A review and meta-analysis of mostly observational data from adults found FMT to be 80 to 90 percent effective.
Data in children are limited to small case series, which prompted me, Maribeth Nicholson at Vanderbilt University and other colleagues to develop the National Pediatric FMT Registry. To date we have enrolled 373 pediatric patients with recurrent C. diff who received FMT in various forms at 18 centers across the U.S.1
The cure rate at two months post-FMT was 81 percent. Of the 19 percent of children who relapsed, about half got repeat FMT. About 57 percent of these repeat treatments were successful, for an overall success rate of 87 percent. Patients receiving fresh (versus frozen) stool tended to have better outcomes, as did those receiving stool via colonoscopy. Serious adverse events were rare (affecting 1.6 percent), though 9.6 percent had minor GI side effects and 5 percent experienced an IBD flare. Our final report on this patient cohort will be published this spring.
FMT for other conditions
FMT has been tested in at least a dozen studies for IBD without C. diff, mostly ulcerative colitis. Results have been mixed: Some patients enter remission, some have no change and some have worsening symptoms. We recently launched our own pediatric trials of FMT for Crohn’s and ulcerative colitis; both are still recruiting patients.
Studies have looked at FMT for a variety of other conditions including drug-resistant organisms, chronic intestinal pseudo-obstruction, graft-versus-host disease, metabolic syndrome and autism. However, well designed clinical trials looking at efficacy are still needed. It is also important to remember that FMT is considered an experimental therapy and should not be done at home without medical supervision. Information about approved clinical trials for FMT is available at the ClinicalTrials.gov website.
What’s the bottom line?
We know that FMT is safe and effective in children with recurrent C. diff. Adverse events are mostly mild (constipation, diarrhea, gas). FMT holds tremendous potential for other conditions, and numerous studies are ongoing. But currently, data are scant, especially in children. We need prospective, randomized studies to properly evaluate FMT and to understand how best to deliver it, in what form and at what dose. For the most meaningful and enlightening results, these studies should involve clinicians, microbiologists, and computational scientists.
Interested in FMT for recurrent C. difficile, or in our studies of FMT for IBD? Email us at FMT@childrens.harvard.edu.