Sex‐ and Time‐Resolved Physiological and Gut Ecosystem Responses to a Food‐Grade Microbiome‐Targeted Intervention in Collegiate Endurance Athletes

Endurance athletes experience sustained physiological demands during high-volume training, yet evidence for microbiome-targeted interventions in real-world settings remains limited. We conducted a two-stage, randomized, double-blind, placebo-controlled trial in 150 athletes allocated 2:1 to combined probiotics-yeast extract (CPYE) or placebo for 6 weeks; 44 completers confirmed for the 12th Inner Mongolia Autonomous Region University Games entered an exploratory 6-week extension with intensified training. Integrating wearable-derived phenotyping, field-based cardiorespiratory indices, clinical assessments, fecal metagenomics, and metabolomics, we found that during the randomized short-term phase, CPYE was associated with changes in device-estimated maximal oxygen uptake, exercise heart-rate indices, lactate, and redox biomarkers versus placebo. Exploratory sex-stratified analyses suggested heterogeneous response patterns, while the selected long-term extension indicated time-dependent changes requiring confirmation. Multi-omics identified sex- and phase-associated differences in microbial taxa, functions, metabolites, and network topology. Indirect-effect models nominated candidate features (rmlD, PISD-linked phosphatidylethanolamine pathways, Bacteroides ovatus, and folate-related functions) as potential indirect correlates of host outcomes. These findings support further evaluation of CPYE-associated responses in collegiate endurance athletes; subgroup, long-term, network, and indirect-effect results are hypothesis-generating.