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

The trial hypothesizes that youth-derived fecal microbiota transplantation can remodel the gut microecosystem and improve clinical outcomes in adults with T1DM.

• The study is premised on the established role of gut microbiota dysbiosis in type 1 diabetes mellitus (T1DM)
• FMT is described as 'a novel therapeutic avenue' for T1DM
• The specific use of youth-derived donors distinguishes this protocol from standard FMT approaches
• This is a protocol paper, meaning no efficacy results are yet reported

The trial is designed as a single-center, randomized, double-blind, placebo-controlled pilot study enrolling adults with T1DM who have suboptimal glycemic outcomes.

• Eligible participants must have glycated hemoglobin (HbA1c) of 7.0–14.0% or time in range (TIR) <70%
• Participants are randomly allocated 1:1 to receive either yFMT or placebo capsules
• The intervention consists of 6 consecutive days of capsule administration alongside standard insulin therapy
• A 12-week follow-up period follows the intervention
• The trial is registered in the Chinese Clinical Trial Registry with identifier ChiCTR2500111955 (registered November 7, 2025)

The trial includes a 17-day run-in period prior to randomization for insulin optimization, continuous glucose monitoring setup, baseline assessments, and bowel preparation.

• Continuous glucose monitoring (CGM) is worn during the run-in and follow-up periods
• Insulin optimization during run-in aims to standardize glycemic management before intervention
• Bowel preparation is conducted as part of the pre-intervention protocol
• Baseline assessments are completed during this run-in phase

The primary efficacy endpoint is the change from baseline in the rate of achieving a composite glycemic target at 12 weeks post-randomization.

• The composite target is defined as TIR >70% and time below range (TBR) <4% simultaneously
• This endpoint reflects clinically meaningful glycemic control thresholds used in diabetes management
• The composite target aligns with established continuous glucose monitoring-based glycemic benchmarks

Secondary efficacy endpoints encompass a broad range of glycemic, immunological, microbiological, and metabolomic outcomes measured at weeks 4 and 12.

• Glycemic secondary endpoints include HbA1c, fasting plasma glucose, 2-hour postprandial glucose, and additional CGM metrics
• Non-glycemic endpoints include C-peptide levels, immune responses, and infection markers
• Gut microbiota composition changes are assessed at weeks 4 and 12
• Serum metabolomic profiles including bile acids, short-chain fatty acids, and related metabolites are assessed at week 12
• The composite achievement rate is also assessed as a secondary endpoint at 4 weeks post-intervention

Feasibility will be assessed through multiple operationalized metrics including recruitment rate, retention rate, intervention adherence, and acceptability.

• These feasibility metrics are designed to provide the necessary evidence to power a subsequent multicenter large-scale study
• Safety endpoints include the incidence of adverse events and serious adverse events
• The authors describe the study as a 'pilot' trial, indicating it is not powered for definitive efficacy conclusions

Exploratory biomarker analyses are planned within the trial to support future individualized microbiome-based therapeutics.

• The authors state these analyses 'may further pave the way for future individualized microbiome-based therapeutics'
• Biomarker analyses complement the primary and secondary endpoints
• The inclusion of metabolomics (bile acids, short-chain fatty acids) reflects interest in mechanistic pathways linking gut microbiota to glycemic outcomes