Daily, Oral FMT for Longterm Maintenance Therapy in Ulcerative Colitis: Results of a single-center, prospective, randomized pilot study.

Abstract

BackgroundFecal 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 fecal microbiota transplantation (FMT) in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT). MethodsSubjects 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. ResultsTwelve 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 treatment. 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. ConclusionThese 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.

Hot topics on fecal microbiota transplantation for the treatment of inflammatory bowel disease

“…In addition, no significant difference in FMT maintenance between an enema and oral capsule delivery was observed (91). Therefore, oral FMT capsules are a promising drug delivery option for long-term use to maintain a stable gut microbiota structure (21). More RCTs on oral capsule-administered FMT with high acceptability are required.…”

“…For a new treatment regimen for IBD, the public is most concerned about safety and efficacy. Most patients experience only transient discomfort, such as diarrhea, abdominal pain, bloating, borborygmus, nausea, vomiting, and increase in C-reactive protein level (17,21,22,25,26,29,31,32,(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63), which are believed to be an immune response caused by the infused fecal microbiota. There are also a small number of patients who have narcolepsy, fatigue (61), skin pruritus (29,52,62), testicular pain, rectal abscess (18), perianal pain or fistula (26), blood in the stool (27,57), herpes zoster (57), and other complaints (64).…”

“…Therefore, an oral capsule-based FMT has recently attracted attention. In previous studies, oral capsule FMT was generally used as an adjunctive therapy (21,(89)(90)(91). A small sample-sized open-label study showed that oral capsule FMT can temporarily improve patients' quality of life and reduce calprotectin (92).…”

“…This delivery method requires that the capsules are always stored at −20 • C and should not be directly transferred between refrigerators. If transfer is required, it should be kept on dry ice at all times to maintain the microbiota's viability (21). It is difficult to link these three stool processes before drug delivery to IBD efficacy without RCTs that control for other potentially confounding variables.…”

“…[17][18][19][20][21][22]. Moayyedi et al recruited 75 patients with mild-severe UC (38 received FMT and 37 received placebo) and demonstrated that patients who received fecal enemas from donors (24%) had significantly higher rates of clinical remission at week 7 than those in the placebo enema group (5%) (p = 0.03).…”