Page 18 - Introduction to FMT

FMT Introduction

The selection of a donor for FMT is not standardized, although there is general consensus for the need to
do so [36]. Initially, donors were typically family members identified by the patient. However, recent
studies highlight the practical advantages of using standardized volunteer donors and creating screened
biobanks [31,34]. In general, donors are screened for healthy bowel movements according to the Bristol
stool chart, communicable diseases, recent travel history and antibiotic history.

In subsequent publications and conferences, Vrieze et al. noted that the patients who had a more robust
improvement of insulin sensitivity after FMT received transplantation from the same limited number of
donors [37]. That is, a minority of donor samples elicited a robust response, whereas other samples had
no effect on patients’ metabolism. The success of the intervention, hence, could be attributed to “super-
donors.” Studies on the effects of FMT in alleviating symptoms of IBD have similarly observed that fecal
samples from certain donors have a much greater therapeutic effect on multiple recipients [38]. Currently
there is no way to identify super-donors until after experiments have started. More recent FMT studies try
to identify super-donors earlier in order to perform more rigorous analysis of their microbiome for the
identification of therapeutic microbiota, which could allow for the design of a better alternative to FMT.

There is a strong social stigma with FMT [39]. Because fecal matter is difficult to standardize, the ethical
and social complications in transplanting feces, and the difficulty in monetization, alternatives to direct
FMT are being actively pursued [40]. Gel capsules of fecal microbiota is a promising new technique which
excludes the need for any gastrointestinal procedure [34,41] and is preferred by patients [42,43]. In fact,
private companies already deliver FMT through oral capsules, mainly for the treatment of CDI. However, it
is unclear whether these capsules are as effective as FMT itself.

Another potential treatment is to design and produce probiotics in a donor-independent fashion. For
example, the Vrieze et al., study identified increased butyrate-producing microbes in patients with

Go to: increased insulin sensitivity following FMT [8]. If the increase of butyrate-producing bacteria is
important for improvement of metabolic symptoms, then there is a possibility for more direct treatment
of metabolic syndrome through pro/pre-biotics, which would be easier to control and administer.

Potential Risks

One challenge with FMT is the difficulty in finding accurate measures of adverse reactions. Thus far, a
vast majority of recipients are ill and it is difficult to differentiate between normal disease progression and
the effects of FMT. Nevertheless, although hundreds of individuals have undergone FMT, few negative
outcomes have been reported, even in immunocompromised patients [44]. The majority of negative
symptoms reported are mild, including diarrhea or fever [45-47]. Mortality has been observed in FMT
trials, however it was attributed to unrelated causes in severely ill or elderly patients. Microbiota can
predispose susceptibility to atherosclerosis using causative evidence in mice and correlative evidence in
humans [48]. In addition, the spread of transmissible disease, while not reported, is still a viable threat,
especially to the immunocompromised (e.g. IBD patient on immunomodulatory therapy, HIV patient with
CDI). These reports underscore the importance of rigorous donor screening. Finally, these risks have to be
tempered with the morbidity and mortality associated with obesity and its associated metabolic
diseases, which as of yet have few effective treatments.

FMT Introduction