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

BMC Gastroenterology

Nathaniel D. Chu¹  Le Thanh Tu Nguyen¹  Eric J. Alm¹  Peter Callas²  Mario Velez³  Karen Fortner³  Cheryl Collins³  Aaron Cohn³  Magen Phillips³  Ralph Budd⁴  Brigitte Lavoie⁵  Gary M. Mawe⁵  Jessica W. Crothers⁶  Rebecca Wilcox⁶  Mark Smith⁷  Zain Kassam⁷  Elaine Vo⁷  Roxana Del Rio-Guerra⁸  Peter L. Moses⁹  Wing Fei Wong^1,10  Ryan J. Elliott^1,10 

[1] Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, MA, USA;Center for Microbiome Informatics and Therapeutics, Broad Institute, Cambridge, MA, USA;Department of Medical Biostatistics, University of Vermont, 89 Beaumont Ave, 05401, Burlington, VT, USA;Department of Medicine, University of Vermont Medical Center, 111 Colchester Ave, 05401, Burlington, VT, USA;Department of Medicine, University of Vermont Medical Center, 111 Colchester Ave, 05401, Burlington, VT, USA;Larner College of Medicine, The University of Vermont, 89 Beaumont Ave, 05401, Burlington, VT, USA;Department of Neurological Sciences, Larner College of Medicine, University of Vermont, 89 Beaumont Ave, 05401, Burlington, VT, USA;Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, 111 Colchester Ave, 05401, Burlington, VT, USA;Larner College of Medicine, The University of Vermont, 89 Beaumont Ave, 05401, Burlington, VT, USA;Finch Therapeutics, 200 Inner Belt Rd, 02143, Somerville, MA, USA;Flow Cytometry and Cell Sorting Facility, Department of Surgery, Larner College of Medicine, University of Vermont, 89 Beaumont Ave, 05401, Burlington, VT, USA;Larner College of Medicine, The University of Vermont, 89 Beaumont Ave, 05401, Burlington, VT, USA;Finch Therapeutics, 200 Inner Belt Rd, 02143, Somerville, MA, USA;OpenBiome, 2067 Massachusetts Ave, 02140, Cambridge, MA, USA;

关键词: Fecal microbiota transplantation;    FMT;    Inflammatory bowel disease;    IBD;    MAIT cells;    Ulcerative colitis;    UC;    Microbiome;    Microbiota;   

DOI  :  10.1186/s12876-021-01856-9

来源: Springer

【 摘 要 】

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 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 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.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.

【 授权许可】

CC BY