Fecal Transplantation: Any Real Hope for Inflammatory Bowel Disease?

Paul Moayyedi

Disclosures

Curr Opin Gastroenterol. 2016;32(4):282-286. 

In This Article

Challenges of Fecal Microbial Transplantation in Inflammatory Bowel Disease

There are emerging data that the microbiome plays an important role in diseases outside of the gastrointestinal tract.[23] Animal models have suggested that the microbiota may influence mental health,[24] obesity[25] as well as a variety of other conditions. Whilst FMT used for IBD has not been associated with any severe adverse events, it is possible that this intervention may cause harm if the donor is not chosen carefully. There has been a case report[26] of FMT being associated with weight gain in a woman successfully treated for C. difficile. This is a single case report, and there are many reasons why a woman might gain weight other than receiving FMT. Nevertheless, this emphasizes the need to follow up IBD patients treated with FMT carefully so that we can fully understand any possible harm with this therapy as well as benefits.[27]

Position statements on FMT for antibiotic resistant C. difficile-associated diarrhea have commented that there needs to be better standardization of the intervention.[28] This applies to an even greater extent to IBD. FMT seems to have a wide therapeutic window for treating C. difficile but this does not seem to be the case for IBD. How the intervention is given is therefore likely to be very important.[27] This article uses the term FMT as an abbreviation for 'fecal microbial transplantation' and the words fecal transplant also appear in the title. This convention is used by most authors on this topic but is semantically incorrect. Emerging data do not support the concept that a substantial proportion of the microbiota from healthy individuals are 'transplanted' to the host. Moayyedi et al. noted that there was a significant shift in the microbiota towards the donor in those that received FMT. However, this shift was modest and the best estimate was that there was a 10% shift of the microbiota species towards the donor. This is similar to that reported by other authors,[29,30] with deep sequencing in one individual pre and post FMT suggesting only 10% of donor microbiota persisting.[30] The term FMT should be used to denote 'fecal microbiota therapy' rather than transplant. This point is not just related to semantics as it speaks to the root of what we are achieving in IBD patients. FMT does change intestinal microbiota but in more subtle ways than the word 'transplant' would suggest. It is important that we understand what changes we are trying to achieve if we are to improve current FMT therapy.

A RCT[31] has shown that frozen then thawed stool is as effective as fresh stool for antibiotic resistant C. difficile-associated diarrhea. Similar studies need to be carried out in IBD to evaluate whether this is also true in Crohn's disease and ulcerative colitis. One study has suggested that the response to FMT may be donor dependent and this needs further exploration if we are to maximize the impact of this approach. FMT protocols also vary as to whether bowel preparation is given beforehand if patients are given antibiotics (and what antibiotics they are given). Again, RCTs are needed to evaluate what is the most effective protocol to give to ulcerative colitis and Crohn's disease patients. Route of administration is also important and may well be different between Crohn's disease and ulcerative colitis patients. The latter may respond better to direct colonic administration of FMT and this may also apply to antibiotic resistant C. difficile-associated diarrhea.[32] The most appropriate placebo to use in RCTs is also important to delineate. Water or physiological saline would be the most inert control to use but the person giving the FMT would not be blinded as to treatment allocation. To avoid this, some have used autologous stool for FMT.[19] However, during autologous preparation it is possible that the organisms that are driving IBD may not thrive outside of the body whereas other bacteria may still flourish. It is theoretically possible, therefore, that autologous stool could be therapeutic and this may also not be the ideal control preparation.

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