This two-cohort study (Rotterdam Study, n=1,249, mean age 62.7y; Framingham Heart Study, n=1,227, mean age 55.2y) examined associations between gut microbiome composition (16S rRNA sequencing + PICRUSt2 functional prediction) and DXA-derived musculoskeletal phenotypes — appendicular lean mass (ALM), femoral neck BMD, and trabecular bone score (TBS) — in community-dwelling middle-aged and older adults.
Alpha diversity showed no association with any musculoskeletal phenotype after multiple testing correction; beta diversity was associated with ALM in combined and female analyses. Four genera linked to higher ALM: lower *Oscillibacter* (β=−0.51), *Anaerotruncus* (β=−0.41), *Eisenbergiella* (β=−0.39), and higher *Agathobacter* (β=0.40). In females specifically, lower *Anaerotruncus*, *Hungatella*, and *Clostridiales* DTU089, plus higher biotin biosynthesis II pathway activity, were associated with higher ALM. No robust associations were found for bone traits (FN-BMD or TBS).
- Cross-sectional design prevents causal inference between microbiome composition and muscle mass. - 16S rRNA sequencing provides genus-level resolution only; functional pathways are predicted (PICRUSt2), not directly measured. - Findings need replication in larger cohorts before mechanisms can be clarified.
No actionable clinical changes are warranted yet — gut microbiome profiling is not ready for routine musculoskeletal risk assessment. These hypothesis-generating findings may guide future research into microbiome-targeted strategies for muscle mass preservation in older adults, particularly in women.
