Research Article: Fecal Transplants: What Is Being Transferred?

Date Published: July 12, 2016

Publisher: Public Library of Science

Author(s): Diana P. Bojanova, Seth R. Bordenstein

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.

Partial Text: 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. In humans, 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. For the purposes of this essay, we will use the catch-all phrase of “fecal transplants” to refer to all types of procedures. Fig 1 shows the very recent growth of the term in PubMed references involving both human and model system studies.

Human fecal composition has not been intensively studied. The studies that have examined composition are mostly from the 1970s and 1980s and report varying results, perhaps because of variation in diet and health. On average, adult fecal matter is estimated to be 75% water and 25% solid matter [17]. The vast majority of solid matter is organic material, whose makeup consists of 25%–54% microbial cells (with a slight portion likely consisting of viruses) that may be alive or dead [18]. As microbial counts were based on light microscopy and a modification of the Gram stain, the microbial cells were presumed to be mostly bacteria [18], but quality evidence is lacking. Several other components are found in significant concentration, including archaea, fungi, and microbial eukaryotes. One particular methanoarchaeon species, Methanobrevibacter smithii, was detected in 95.7% of patients spanning infants, adults, and the elderly [19], and it can comprise up to 10% of all fecal anaerobes [20]. Viable colonocytes are also readily isolated from newborn and adult feces [21–23]. No analysis of their potential contribution to the success of fecal transplants has been reported. Independent validations of these estimates are needed, particularly measurements that consider all of the entities at once.

Here, we cautiously note that bacteria, either viable or unviable in transferred fecal material, may not be the only player in donor feces that affects the recipient’s biology. On the one hand, the effects of bacteria on CDI or animal model traits such as obesity [100] and toxin tolerance [101] appear well justified thus far. On the other hand, in a broader context where fecal transplants are solely utilized in animal model studies and other human diseases, judicious reductionism seems warranted in light of a limited understanding of the complex nature of feces. Deconstructing the benefit and interactions of constituent parts of fecal matter will clarify the relative importance and causality of each of these components and the potential development of specific therapies.

Source:

http://doi.org/10.1371/journal.pbio.1002503