Efficacy and safety of Youth-derived Fecal Microbiota Transplantation among adults with Type 1 Diabetes Mellitus: A protocol of pilot randomized controlled trial

BackgroundDysbiosis of gut microbiota plays a key role in type 1 diabetes mellitus (T1DM). Fecal microbiota transplantation represents a novel therapeutic avenue. We hypothesize that youth-derived fecal microbiota transplantation (yFMT) can remodel the gut microecosystem and improve clinical outcomes. This study aims to investigate the efficacy and safety of orally administered yFMT capsules in adults with T1DM. Methods and analysisThis single-center, randomized, double-blind, placebo-controlled pilot study will enroll adults with T1DM who have suboptimal glycemic outcomes (glycated hemoglobin[HbA1c] of 7-14% and time in range [TIR] <70%). Following a 17-day run-in period for insulin optimization, continuous glucose monitoring(CGM) wearing, baseline assessments and bowel preparation, participants will be randomly allocated (1:1) to take yFMT or placebo capsules for consecutive 6 days, alongside their standard insulin therapy, and then complete a 12-week follow-up. The primary efficacy endpoint is the change from baseline in the rate of achieving the composite target of TIR>70% and time below range<4% at 4 and 12 weeks post-randomization. Secondary efficacy endpoints comprise changes from baseline at weeks 4 and 12 in other glycemic metrics (including HbA1c, fasting glucose, 2-hour postprandial glucose, and additional CGM metrics), C-peptide, immune responses, infection markers, and gut microbiota composition. Changes from baseline at week 12 in serum metabolomic profiles will also be assessed, encompassing bile acids, short-chain fatty acids, and other related metabolites. Safety endpoints include the incidence of adverse events and serious adverse events. DiscussionOur findings will offer new insight into the feasibility and effects of oral yFMT in adult with T1DM and provide the necessary evidence to power a subsequent multicenter large-scale study. Exploratory biomarker analyses conducted within this study may further pave the way for future individualized microbiome-based therapeutics. Trial registrationChinese Clinical Trial Registry identifier: ChiCTR2500111955 (November 7, 2025).