Abstract and Introduction
The community of microorganisms within the human gut (or microbiota) is critical to health and functions with a level of complexity comparable to that of an organ system. Alterations of this ecology (or dysbiosis) have been implicated in a number of disease states, and the prototypical example is Clostridium difficile infection (CDI). Fecal microbiota transplantation (FMT) has been demonstrated to durably alter the gut microbiota of the recipient and has shown efficacy in the treatment of patients with recurrent CDI. There is hope that FMT may eventually prove beneficial for the treatment of other diseases associated with alterations in gut microbiota, such as inflammatory bowel disease, irritable bowel syndrome, and metabolic syndrome, to name a few. Although the basic principles that underlie the mechanisms by which FMT shows therapeutic efficacy in CDI are becoming apparent, further research is needed to understand the possible role of FMT in these other conditions. Although relatively simple to perform, questions regarding both short-term and long-term safety as well as the complex and rapidly evolving regulatory landscape has limited widespread use. Future work will focus on establishing best practices and more robust safety data than exist currently, as well as refining FMT beyond current "whole-stool" transplants to increase safety and tolerability. Encapsulated formulations, full-spectrum stool-based products, and defined microbial consortia are all in the immediate future.
It is now understood that the gut microbiota coevolved with the human host over thousands of years and is integral to overall human physiology, playing a pivotal role in metabolism, immune system function, and maintenance of gut homeostasis.[1,2] Fecal microbiota transplantation (FMT) involves administration of fecal material containing distal gut microbiota from a healthy person (donor) to a patient with a disease or condition related to dysbiosis or an alteration in their normal gut microbiota. The goal of FMT is to treat disease by restoring phylogenetic diversity and microbiota more typical of a healthy person.
Although previously considered fringe therapy and the last resort for patients with Clostridium difficile infection (CDI), FMT has become more widely practiced, and interest in FMT by patients, researchers, and industry has surged over the past 2 to 3 years. Numerous case reports, retrospective case series, and a single randomized controlled trial have shown benefit of FMT in patients with severe or recurrent CDI, with cure rates as high as 100% and a mean cure rate of 87% to 90% for the >500 cases reported in the world literature to date.[3–5] Moreover, the restoration of more typical microbial communities, which come to resemble those of the donor after transplant, persists in a durable fashion after FMT.[6,7] This has resulted in speculation that FMT may eventually prove beneficial in other conditions associated with dysbiosis, such as inflammatory bowel disease (IBD), metabolic syndrome, and many others. This overview describes the history of FMT, basic methodologies, and the potential mechanisms of effect in CDI and other diseases. Data on efficacy are also presented, including a review of the real and theoretical risks of the procedure. In addition, this overview provides a discussion of the future of microbial-based therapeutics and the complex regulatory issues around this rapidly evolving field.
Gastroenterology. 2015;149(1):223-237. © 2015 AGA Institute