Randomized, double-blind, placebo-controlled trial of fecal microbiota transplantation from young physically active donors to promote resilient aging: clinical trial protocol (ARMOR study)

Background: Sarcopenia, characterized by the progressive loss of skeletal muscle mass and strength in older adults, is a key determinant of frailty and functional decline. Affecting up to 15% of individuals aged 65–80 years and more than 50% of those over 80, sarcopenia not only compromises physical autonomy but also increases the risk of metabolic dysfunction and cognitive decline. Emerging evidence suggests that age-related gut microbiota dysbiosis contributes to these impairments by reducing microbial diversity and altering host metabolic signaling, leading to chronic inflammation and mitochondrial dysfunction. The present study aims to evaluate the safety, tolerability, and preliminary efficacy of oral fecal microbiota transplantation derived from young, physically active donors administered to older adults, focusing on outcomes related to functional autonomy, muscle performance, metabolism and cognition. Methods: This is a double-blind, randomized, placebo-controlled clinical trial involving community-dwelling adults aged 65–84 years. Participants will be randomized 1:1 to receive either FMT capsules or placebo following a short course of oral rifaximin (or placebo). Assessments will be performed at baseline and at 4, 8, and 20 weeks post-intervention. The primary outcomes are safety and tolerability, as well as changes in the Global Index of Functional Autonomy (GDLAM battery) and muscle strength. Secondary outcomes include gait speed, body composition (DXA), metabolic biomarkers, gut microbiota composition (shotgun metagenomics), cognitive performance, and psychological well-being. Expected impact: By restoring microbial diversity and function, FMT from young, active donors may enhance muscle quality, cognitive resilience, and metabolic health in older adults. This study introduces a novel, non-invasive therapeutic approach based on lyophilized and encapsulated microbiota, offering a feasible and scalable strategy to promote healthy aging. Trial registration: ClinicalTrials.gov NCT06649981. Date of registration October 21, 2024.