Across two large population-based cohorts totaling 2,476 middle-aged and older adults (Rotterdam Study and Framingham Heart Study), specific gut bacterial genera showed consistent associations with appendicular lean mass (ALM) — a validated proxy for total skeletal muscle. Lower abundance of Oscillibacter, Anaerotruncus, and Eisenbergiella, combined with higher Agathobacter, correlated with greater ALM. In females specifically, lower Hungatella and Clostridiales DTU089, plus higher microbial biotin biosynthesis II pathway activity, independently associated with higher ALM. Notably, no robust associations emerged for femoral neck bone mineral density or trabecular bone score.
The muscle-microbiome axis is mechanistically plausible — short-chain fatty acids, inflammatory signaling, and B-vitamin synthesis (biotin's role here is intriguing) all modulate skeletal muscle protein turnover. What distinguishes this work is its replication across two independent cohorts with harmonized DXA phenotyping, elevating confidence above typical single-cohort microbiome studies plagued by false discovery. The sex-specific findings align with emerging evidence that estrogen shapes both microbiome composition and muscle metabolism differently than androgens do. Critical limitations remain: 16S rRNA sequencing offers genus-level resolution without functional precision, PICRUSt2-predicted pathways are computational estimates rather than measured metabolites, and the cross-sectional design precludes causal inference. The null bone findings also challenge some animal model predictions. Overall, this is confirmatory and hypothesis-generating rather than paradigm-shifting, but it meaningfully narrows the target genera worth investigating in longitudinal or interventional sarcopenia research.
