Efficacy, safety, and feasibility of youth-derived fecal microbiota transplantation among adults with type 1 diabetes mellitus: A protocol of Pilot Randomized Controlled Trial.

BACKGROUND

Dysbiosis 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 pilot trial aims to assess the feasibility, safety, and preliminary efficacy of yFMT in adults with T1DM.

METHODS AND ANALYSIS: This single-center, randomized, double-blind, placebo-controlled pilot study will enroll adults with T1DM who have suboptimal glycemic outcomes (glycated hemoglobin [HbA1c] of 7.0-14.0% or 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 6 consecutive 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 12 weeks post-randomization. Secondary efficacy endpoints include: (1) the change from baseline in the same composite achievement rate at 4 weeks post-intervention; (2) changes from baseline at Weeks 4 and 12 in other glycemic metrics (including HbA1c, fasting plasma glucose, 2-hour postprandial glucose, and additional CGM metrics), C-peptide, immune responses, infection markers, and gut microbiota composition; and (3) changes from baseline at Week 12 in serum metabolomic profiles (bile acids, short-chain fatty acids, and other related metabolites). Feasibility will be assessed through recruitment rate, retention rate, intervention adherence, and acceptability. Safety endpoints include the incidence of adverse events and serious adverse events.

DISCUSSION: Our findings will offer new insight into the feasibility and effects of oral yFMT capsules in adults 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 REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR2500111955 (November 7, 2025).