Fecal microbiota transplant is thought to help restore the diversity of microbiota in the gut and allow restoration of colonization resistance.
Knowledge about the microbes that coexist with the human organism and the role they may play in both illness and health has exploded in the last 10 years. Of the many functions performed by the fecal flora, now termed fecal microbiota, protection from intestinal infections is primary. Clostridium difficile infection (CDI), which usually results when antibiotics alter the microbiome, is a prime example of disrupting a normally peaceful and mutually beneficial coexistence.
Because antibiotics are also necessary to treat CDI, the microbiome remains altered and inhospitable to return of endemic microbiota. The result is often recurrent CDI (RCDI) which is difficult to treat and can be responsible for significant morbidity and mortality.
The idea of using stool from healthy donors to repopulate the colon microbiota dates back centuries, but has gained modern attention over the last 15 years as an effective therapy. Many case reports and small series have shown efficacy of donor stool to treat RCDI with response rates of 90% overall.1,2 Importantly, a recent randomized controlled trial proved efficacy in patients with RCDI when donor stool was given by nasoduodenal infusion.3
The process of fecal microbiota transplant (FMT) involves choosing appropriate patients and donors; screening the selected donor; and administration of the stool. Step 1, selecting the right patient, is critical. FMT appears effective to treat RCDI. Guidelines for the diagnosis, treatment, and prevention of RCDI suggest that repeat antibiotic therapy may work for the first 2 recurrences.4 An easy regimen is to give vancomycin 125 mg, 4 times daily for 10 days followed by a single dose every 3 days, for a total of 10 more doses.4 If this pulse regimen fails, it is reasonable to consider FMT as the next option.
There are case reports of FMT for treatment of severe refractory CDI but, unlike RCDI, there are no randomized controlled studies, fewer cases reported, and no guidelines to indicate when it should be considered and when it would be dangerous. Other uses of FMT are speculative at this point, although studies of FMT in inflammatory bowel disease are in process.
The second step is to choose a donor. The preference is for an intimate long-time partner, but that person should be healthy, with no history of chronic illnesses, cancer, gastrointestinal illnesses, and recent use of antibiotics, among others. There are currently no universally agreed upon donor selection criteria or criteria for screening, but the protocol should be similar to that for blood donors.
Third, the donor’s stool and blood are screened for viral and bacterial pathogens, to maximize safety. A consensus paper several years ago written by those familiar with FMT5 recommended screening criteria, but there has been no consensus issued by any professional organization. Such criteria would be welcome to standardize the approach. At a minimum, stool should be screened for enteric pathogens including C. difficile and parasites, and blood should be screened for hepatitis A, B, and C; HIV types 1 and 2; and, syphilis. The recipient’s blood should be screened for the same pathogens. The process can take up to 2 weeks. Ideally the donor should be screened within 4 weeks of making the “donation.” Even with insurance, this testing can cost several hundred dollars out-of-pocket. Some institutions currently are paying for the donor screening tests.
Finally, fresh stool is obtained, ideally passed within 6 hours, and administered to the patient who has been prepared by gut lavage. Stool is introduced into the GI tract by the upper route (nasogastric or nasoduodenal tube) or by the lower route (enema, sigmoidoscopy, or colonoscopy). The most effective route is not known, but review of studies suggests the lower route may be slightly more effective. The treating antibiotic is usually continued for 1 to 3 days prior to the transplant. For patients who have had sudden onset of severe recurrences, it can be continued until the day prior the FMT.
Why does it work?
Studies show a decreased diversity of the microbiota in patients with RCDI compared to controls and to patients who had a single episode of CDI without recurrences.6 Studies of recipient stool show that it is similar to donor stool and that this persists for at least a month. This appears to allow restoration of colonization resistance that prevents further infection from CDI.
While aesthetically unappealing, FMT appears safe with no identified long term sequelae or adverse events, although 2 cases of self-limited viral gastroenteritis transmitted from the donor have been reported. Patient acceptance is excellent, with some patients remarking on how quickly they respond. I have practiced gastroenterology at a county hospital for over 30 years, and these are some of my most grateful patients.
Currently we do not know how widespread the practice of FMT has become in the US. In May, 2013, the FDA suggested that anyone performing the procedure should obtain an investigational new drug application, but several months later the agency softened this recommendation. Some have suggested establishment of a registry to document efficacy and long term results and possible complications, but this does not currently exist. An NIH-funded study of FMT via colonoscopy for RCDI is underway; results will be of great interest.
What does the future hold?
Likely we will see standardization of methodology, screening, techniques, and ultimately preparations of the key bacteria needed to restore normal microbial homeostasis. For now, this approach is fascinating for the light it sheds on one of the important roles of the fecal microbiota.
1. Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011;53:994-1002.
2. Kassam A, Lee CH, Yuanand Y, Hun RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis.Am J Gastroenterol. 2013;108:500-508.
3. van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368:407-415.
4. Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108:478-498; quiz 499.
5. Bakken JS, Borody T, Brandt LJ, et al. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol. 2011;9:1044-1049.
6. Chang JY, Antonopoulos DA, Kalra A, et al. Decreased diversity of the fecal microbiome in recurrent Clostridium difficile-associated diarrhea. J Infect Dis. 2008;197:435-438.