Abstract
Fecal transplants are increasingly utilized for treatment of recurrent infections (i.e., Clostridium difficile) in the human gut and as a general research tool for gain-of-function experiments (i.e., gavage of fecal pellets) in animal models. Changes observed in the recipient's biology are routinely attributed to bacterial cells in the donor feces (~1011 per gram of human wet stool). Here, we examine the literature and summarize findings on the composition of fecal matter in order to raise cautiously the profile of its multipart nature. In addition to viable bacteria, which may make up a small fraction of total fecal matter, other components in unprocessed human feces include colonocytes (~107 per gram of wet stool), archaea (~108 per gram of wet stool), viruses (~108 per gram of wet stool), fungi (~106 per gram of wet stool), protists, and metabolites. Thus, while speculative at this point and contingent on the transplant procedure and study system, nonbacterial matter could contribute to changes in the recipient's biology. There is a cautious need for continued reductionism to separate out the effects and interactions of each component.
Highlights
A fecal transplant—the transfer of stool or portions of stool from one organism into the gastrointestinal tract of another—is rapidly gaining attention as a treatment for human gut infections and as a tool for functional "knock-in" studies of the microbiota in animal models
The procedure is referred to as fecal microbiota transplantation because the microbial components are typically enriched, and in animal models, the transfer of unprocessed stool is commonly achieved by feeding or oral gavage of fecal matter
Across a collection of studies, human fecal donations from related donors showed slightly higher resolution in Clostridium difficile infection (CDI) cases (93%) compared to unrelated donors (84%) [34]. This observation is notable in light of the recent finding that human genetic variation is significantly correlated with variation in bacterial community composition [35,36]
Summary
A fecal transplant—the transfer of stool or portions of stool from one organism into the gastrointestinal tract of another—is rapidly gaining attention as a treatment for human gut infections and as a tool for functional "knock-in" studies of the microbiota in animal models. To demonstrate that bacteria directly contribute to disease resolution, several research groups have tested whether enriched bacterial portions of fecal material can be effective in treating CDI in mice and humans. Use of a six-species cocktail therapy suppressed recurrent CDI in 92% of mice [10] when approximately 1010 cells per bacterial species were gavaged into recipients In another mouse study, 108 colony-forming units of a single bacterium isolate, Lachnospiraceae D4, caused over a 10-fold reduction in the number of C. difficile colony-forming units per gram of cecal contents [39]. At 26 weeks of treatment, only 0%–5% of patients from various treatment groups had toxigenic C. difficile remaining in feces These studies indicate that cultured bacteria can, in certain cases, be effective contributors to CDI disease resolution. Determining functions may be important in understanding the composite nature of feces and its effects on fecal transplants in humans and/or animal models
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