The association of gut microbiome composition with musculoskeletal features in middle-aged and older adults: A two-cohort joint study

Bones and muscles are connected chemically, anatomically, and functionally. While animal studies suggest the gut microbiome influences musculoskeletal aging, human evidence remains limited. We assessed associations between musculoskeletal phenotypes and gut microbiome composition in community-dwelling middle-aged and older adults.

We analyzed DXA-derived phenotypes from two population-based cohorts: the Rotterdam Study (mean age 62.7 years; n = 1249) and the Framingham Heart Study (mean age 55.2 years; n = 1227). Phenotypes included appendicular lean mass (ALM), femoral neck bone mineral density (FN-BMD), and trabecular bone score (TBS). Gut microbiome composition was assessed via 16S rRNA sequencing, and functional potential predicted using PICRUSt2. Multivariate linear regression analyses were adjusted for demographic, lifestyle, and clinical covariates.

Alpha diversity was not associated with any musculoskeletal phenotype after multiple testing, whereas beta diversity was associated with ALM in the combined and female analyses. Four genera associated with ALM: lower abundance of Oscillibacter (β = -0.51, 95%CI [-0.74,-0.29]), Anaerotruncus (β = -0.41, 95%CI [-0.61,-0.21]), Eisenbergiella (β = -0.39, 95%CI [-0.59,-0.19]) and higher abundance of Agathobacter (β = 0.40, 95%CI [0.20,0.60]) were associated with higher ALM. In females, lower abundance of Anaerotruncus (β = -0.32, 95%CI [-0.45,-0.19]), Hungatella (β = -0.26, 95%CI [-0.38,-0.15]), and Clostridiales bacterium DTU089 (β = -0.37, 95%CI [-0.55,-0.19]), and higher biotin biosynthesis II pathway (β = 0.44, 95%CI [0.24,0.64]) associated with higher ALM. No robust associations were observed for bone traits.

Although no associations were identified between gut microbial features and bone measures, several microbial genera were associated with appendicular lean mass in middle-aged and older adults, with evidence of sex-specific effects. Larger studies are needed to confirm these findings and clarify underlying mechanisms.