Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study

Abstract

Background Fecal microbiota transplantation (FMT) is a promising new strategy in the treatment of Inflammatory Bowel Disease, but long-term delivery systems are lacking. This randomized study was designed as a safety and feasibility study of long-term FMT in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT). Methods Subjects were randomized 1:1 to receive FMT induction by colonoscopy, followed by 12 weeks of daily oral administration of frozen encapsulated cFMT or sham therpay. Subjects were followed for 36 weeks and longitudenal clinical assessments included multiple subjective and objective markers of disease severity. Ribosomal 16S bacterial sequencing was used to assess donor-induced changes in the gut microbiota. Changes in T regulatory (Treg) and mucosal associated invariant T (MAIT) cell populations were evaluated by flow cytometry as an exploratory endpoint. Results Twelve subjects with active UC were randomized: 6 subjects completed the full 12-week course of FMT plus cFMT, and 6 subjects received sham treatment by colonic installation and longitudinal oral placebo capules. Chronic administration of cFMT was found to be safe and well-tolerated but home storage concerns exist. Protocol adherence was high, and none of the study subjects experienced FMT-associated treatment emergent adverse events. Two subjects that received cFMT achieved clinical remission versus none in the placebo group (95% CI = 0.38-infinity, p = 0.45). cFMT was associated with sustained donor-induced shifts in fecal microbial composition. Changes in MAIT cell cytokine production were observed in cFMT recipients and correlated with treatment response. Conclusion These pilot data suggest that daily encapsulated cFMT may extend the durability of index FMT-induced changes in gut bacterial community structure and that an association between MAIT cell cytokine production and clinical response to FMT may exist in UC populations. Oral frozen encapsulated cFMT is a promising FMT delivery system and may be preferred for longterm treatment strategies in UC and other chronic diseases but further evaluations will have to address home storage concerns. Larger trials should be done to explore the benefits of cFMT and to determine its long-term impacts on the colonic microbiome. Trial registration: ClinicalTrials.gov (NCT02390726). Registered 17 March 2015, https://clinicaltrials.gov/ct2/show/NCT02390726?term=NCT02390726&draw=2&rank=1.

Therapeutic Advances in Gut Microbiome Modulation in Patients with Inflammatory Bowel Disease from Pediatrics to Adulthood

“…There is also no unified protocol on the preferred route of fecal administration. Most of the studies use colonoscopy to administer the FMT, but others debate that gastroscopy is an equally effective method [114], while other groups use oral capsules [115].…”

The Communication Between Intestinal Microbiota and Ulcerative Colitis: An Exploration of Pathogenesis, Animal Models, and Potential Therapeutic Strategies

“…To date, multiple randomized controlled trials (RCTs) have explored the efficacy and safety of FMT in the treatment of UC (Table 2). Among them, 5 RCTs showed that the clinical remission rate of FMT in the treatment of UC was significantly different from that of placebo or autologous fecal transplantation, suggesting that FMT has therapeutic effect on UC (150,(152)(153)(154)(155). On the contrast, one study showed that there was no significant difference in the efficacy between FMT and autologous fecal transplantation (156).…”

Encapsulated Fecal Microbiota Transplantation: Development, Efficacy, and Clinical Application

“…There are five randomized clinical trials (RCTs) that investigated FMT in UC ( Moayyedi et al., 2015 ; Rossen et al., 2015 ; Paramsothy et al., 2017a ; Costello et al., 2019 ; Crothers et al., 2021 ). One small pilot RCT has been conducted evaluating FMT in CD ( Sokol et al., 2020 ), but most data come from open-label cohort trials.…”