Fecal microbiota transplantation: great potential with many challenges

Abstract

In January of 2019, Samuel P. Costello and colleagues published a wonderfully executed, double blind placebo-controlled trial on fecal microbiota transplantation (FMT) versus autologous stool as placebo in mild to moderately active adult ulcerative colitis [UC: one type of inflammatory bowel disease (IBD)] patients. This review-commentary examines the current state of knowledge on human gut microbiome (live microbiota + their products and surrounding environment, i.e., fecal matter) and microbial therapeutics from a gastrointestinal (GI) clinician's standpoint. The varied forms of dysbiosis as the target of FMT, recipient donor and placebo considerations are also discussed in respect to randomized control trials in IBD [and the lack thereof in Crohn's disease (CD)] with this unconventional treatment modality.

Keywords: Crohn’s disease (CD); Fecal microbiota transplantation (FMT); microbiome; ulcerative colitis (UC).

Figure 1

Arbitrary categorization of dysbiosis (i.e., altered microbiome composition in disease compared to healthy controls within the same socio-demographic and geographic region). Primary and secondary dysbioses are separated as acute/transient, or chronic/recurrent. Primary dysbioses are more commonly acute/transient as opposed to secondary dysbioses (depicted by arrow thickness). Each type of dysbiosis can be further separated. Note a few specific examples for these further subcategories. It is the primary chronic/recurrent dysbioses, which are the best targets for fecal microbiota transplantation (FMT) or defined microbial therapeutics. For the secondary dysbioses, underlying condition/disease based specific considerations have to be made for FMT. For further details see main text. BMT, bone marrow transplantation; C. diff, Clostridioides difficile; CGD, chronic granulomatous disease; EPEC, entero-pathogenic E. coli; HIV, human immunodeficiency virus; IBD, inflammatory bowel disease; IPEX, immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome; SOT, solid organ transplantation; VRE, vancomycin resistant enterococcus.