PMID- 32150549 OWN - NLM STAT- MEDLINE DCOM- 20200629 LR - 20240423 IS - 1549-1676 (Electronic) IS - 1549-1277 (Print) IS - 1549-1277 (Linking) VI - 17 IP - 3 DP - 2020 Mar TI - Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial. PG - e1003051 LID - 10.1371/journal.pmed.1003051 [doi] LID - e1003051 AB - BACKGROUND: There is intense interest about whether modulating gut microbiota can impact systemic metabolism. We investigated the safety of weekly oral fecal microbiota transplantation (FMT) capsules from healthy lean donors and their ability to alter gut microbiota and improve metabolic outcomes in patients with obesity. METHODS AND FINDINGS: FMT-TRIM was a 12-week double-blind randomized placebo-controlled pilot trial of oral FMT capsules performed at a single US academic medical center. Between August 2016 and April 2018, we randomized 24 adults with obesity and mild-moderate insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] between 2.0 and 8.0) to weekly healthy lean donor FMT versus placebo capsules for 6 weeks. The primary outcome, assessed by intention to treat, was change in insulin sensitivity between 0 and 6 weeks as measured by hyperinsulinemic euglycemic clamps. Additional metabolic parameters were evaluated at 0, 6, and 12 weeks, including HbA1c, body weight, body composition by dual-energy X-ray absorptiometry, and resting energy expenditure by indirect calorimetry. Fecal samples were serially collected and evaluated via 16S V4 rRNA sequencing. Our study population was 71% female, with an average baseline BMI of 38.8 +/- 6.7 kg/m2 and 41.3 +/- 5.1 kg/m2 in the FMT and placebo groups, respectively. There were no statistically significant improvements in insulin sensitivity in the FMT group compared to the placebo group (+5% +/- 12% in FMT group versus -3% +/- 32% in placebo group, mean difference 9%, 95% CI -5% to 28%, p = 0.16). There were no statistically significant differences between groups for most of the other secondary metabolic outcomes, including HOMA-IR (mean difference 0.2, 95% CI -0.9 to 0.9, p = 0.96) and body composition (lean mass mean difference -0.1 kg, 95% CI -1.9 to 1.6 kg, p = 0.87; fat mass mean difference 1.2 kg, 95% CI -0.6 to 3.0 kg, p = 0.18), over the 12-week study. We observed variable engraftment of donor bacterial groups among FMT recipients, which persisted throughout the 12-week study. There were no significant differences in adverse events (AEs) (10 versus 5, p = 0.09), and no serious AEs related to FMT. Limitations of this pilot study are the small sample size, inclusion of participants with relatively mild insulin resistance, and lack of concurrent dietary intervention. CONCLUSIONS: Weekly administration of FMT capsules in adults with obesity results in gut microbiota engraftment in most recipients for at least 12 weeks. Despite engraftment, we did not observe clinically significant metabolic effects during the study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02530385. FAU - Yu, Elaine W AU - Yu EW AD - Endocrine Unit, Division of Endocrinology and Metabolism, Massachusetts General Hospital, Boston, Massachusetts, United States of America. AD - Harvard Medical School, Boston, Massachusetts, United States of America. FAU - Gao, Liu AU - Gao L AUID- ORCID: 0000-0002-9263-5614 AD - Endocrine Unit, Division of Endocrinology and Metabolism, Massachusetts General Hospital, Boston, Massachusetts, United States of America. FAU - Stastka, Petr AU - Stastka P AD - Endocrine Unit, Division of Endocrinology and Metabolism, Massachusetts General Hospital, Boston, Massachusetts, United States of America. FAU - Cheney, Michael C AU - Cheney MC AUID- ORCID: 0000-0002-5145-6521 AD - Endocrine Unit, Division of Endocrinology and Metabolism, Massachusetts General Hospital, Boston, Massachusetts, United States of America. FAU - Mahabamunuge, Jasmin AU - Mahabamunuge J AD - Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America. FAU - Torres Soto, Mariam AU - Torres Soto M AUID- ORCID: 0000-0003-3606-2935 AD - Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America. FAU - Ford, Christopher B AU - Ford CB AUID- ORCID: 0000-0002-4079-8673 AD - Seres Therapeutics, Cambridge, Massachusetts, United States of America. FAU - Bryant, Jessica A AU - Bryant JA AUID- ORCID: 0000-0001-8958-4345 AD - Seres Therapeutics, Cambridge, Massachusetts, United States of America. FAU - Henn, Matthew R AU - Henn MR AUID- ORCID: 0000-0001-8734-5797 AD - Seres Therapeutics, Cambridge, Massachusetts, United States of America. FAU - Hohmann, Elizabeth L AU - Hohmann EL AD - Harvard Medical School, Boston, Massachusetts, United States of America. AD - Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America. LA - eng SI - ClinicalTrials.gov/NCT02530385 GR - P30 DK020579/DK/NIDDK NIH HHS/United States GR - P30 DK040561/DK/NIDDK NIH HHS/United States GR - UL1 TR001102/TR/NCATS NIH HHS/United States GR - UL1 TR002541/TR/NCATS NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200309 PL - United States TA - PLoS Med JT - PLoS medicine JID - 101231360 RN - 0 (Biomarkers) SB - IM MH - Adult MH - Biomarkers/blood MH - Boston MH - Double-Blind Method MH - *Energy Metabolism MH - *Fecal Microbiota Transplantation/adverse effects MH - Female MH - *Gastrointestinal Microbiome MH - Humans MH - *Insulin Resistance MH - Intestines/*microbiology MH - Male MH - Middle Aged MH - Obesity/diagnosis/metabolism/microbiology/*therapy MH - Pilot Projects MH - Time Factors MH - Treatment Outcome PMC - PMC7062239 COIS- I have read the journal's policy and the authors of this manuscript have the following competing interests: EWY has received a research grant from Amgen Inc. and from Doris Duke Charitable Foundation, outside the submitted work. ELH has served as a consultant to Artugen Therapeutics and Matrivax Research and Development Corporation, and has received a research grant from Kaleido, outside the submitted work. CBF, JAB, and MRH are employees of Seres Therapeutics, Inc. All other authors have declared that no competing interests exist. EDAT- 2020/03/10 06:00 MHDA- 2020/07/01 06:00 PMCR- 2020/03/09 CRDT- 2020/03/10 06:00 PHST- 2019/06/21 00:00 [received] PHST- 2020/02/10 00:00 [accepted] PHST- 2020/03/10 06:00 [entrez] PHST- 2020/03/10 06:00 [pubmed] PHST- 2020/07/01 06:00 [medline] PHST- 2020/03/09 00:00 [pmc-release] AID - PMEDICINE-D-19-02285 [pii] AID - 10.1371/journal.pmed.1003051 [doi] PST - epublish SO - PLoS Med. 2020 Mar 9;17(3):e1003051. doi: 10.1371/journal.pmed.1003051. eCollection 2020 Mar.