Fecal Microbiota Transplantation for Gastrointestinal Disorders

Thomas Malikowski; Sahil Khanna; Darrell S. Pardi

Disclosures

Curr Opin Gastroenterol. 2017;33(1):8-13. 

In This Article

Inflammatory Bowel Disease

IBD is a disease characterized by chronic inflammation of the gastrointestinal tract, encompassing both Crohn's disease and ulcerative colitis. Pathogenesis is multifactorial and incompletely understood although immune dysregulation is central to the disease process. Dysbiosis is thought to be associated with either development or exacerbation of underlying disease.

There is substantial evidence that the microbiome is altered in IBD. Studies of the gut microbiota in patients with IBD demonstrate an increase in pathogenic microorganisms while populations of normal commensal phyla are diminished.[40,41] Bacterial RNA sequencing has shown decreased populations of bacteria from the phyla Bacteroidetes and Firmicutes in patients with IBD while pathogenic organisms such as Escherichia coli, Campylobacter species, and Mycobacterium species are increased.[42] Additionally, the patients with IBD have a greater number of bacteria associated with the mucosal surface, with bacterial adherence and invasion being much more prevalent than in healthy controls.[43,44]

Current mainstays of IBD treatment target modulation of the immune system. Often these agents have profound side effects, and in some patients they are either poorly tolerated or ineffective in maintaining disease remission.[45,46] Thus, alternative therapies such as FMT have been pursued. To date there have been numerous observational studies examining the effectiveness of FMT as a therapy for IBD. These observational studies have examined patients with varying level of disease severity and experimented with differing FMT delivery methods and frequency. A review by Coleman and Rubin in 2014[47] synthesized the results of all previously published observational studies and highlighted some encouraging results. Amongst the observation studies, of the 122 patients with IBD who underwent FMT, 45% achieved disease remission. Subgroup analysis found that patients with Crohn's disease were more likely to respond (61%) than patients with ulcerative colitis (22%).[47] Within the last year, a few randomized control trials have been published specific to ulcerative colitis. The first, published by Moayyedi et al.[48] demonstrated a substantial benefit to FMT. Adult patients with ulcerative colitis received six enemas of either FMT or placebo. Patients who received FMT were 17% more likely to achieve remission. A greater proportion of patients with newly diagnosed ulcerative colitis (within 1 year) achieved remission. A second study, published by Rossen et al.,[49] was inconclusive. This study was smaller, including only 48 patients with ulcerative colitis receiving two nasoduodenal infusions of either FMT or placebo. Remission was achieved in 42.2% of patients who received FMT compared to 25.0% of patients receiving placebo; however the difference was not statistically significant. A third study, the FOCUS trial, a randomized control trial comparing FMT to placebo for treatment of ulcerative colitis, is the largest randomized control trial to date. It included 85 patients and defined steroid free clinical and endoscopic remission as primary endpoints. The study found 27% of patients who received FMT achieved remission while only 8% of patients who received placebo did (P < 0.02).[50] Although the results of these randomized studies vary, they provide some important insights. First, they highlight the potential of FMT as a beneficial treatment in ulcerative colitis. Second, the results indicate that the frequency and route of FMT may impact the therapeutic efficacy. Third, they imply that specific subgroups of patients with IBD may respond differently to FMT. Additional, large scale randomized, double-blinded, placebo controlled studies are needed, and the current role of FMT in the treatment of IBD remains unclear. Upon review of clinicaltrials.gov there are currently over 20 studies ongoing, including randomized controlled trials, evaluating the efficacy of FMT for treatment of IBD.

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