Association among lean mass, gut microbiome alterations and bone mineral density in high-altitude

Body composition, particularly lean body mass, plays a pivotal role in skeletal health and has been increasingly linked to the gut microbiota (GM). However, evidence from vulnerable high-altitude populations remains scarce.

This study aimed to evaluate the association between body composition and bone mineral density (BMD) at high altitudes and explore the potential role of GM.

A total of 820 Tibetan participants were recruited. BMD at the lumbar spine (L₁-L₄) and total hip was measured using dual-energy X-ray absorptiometry (DXA). Multivariate linear regression was applied to evaluate the associations between body composition indices and BMD. Participants were stratified into low lean mass index (LLMI) and high lean mass index (HLMI) subgroups using restricted cubic splines (RCS) and body mass index. Stool samples from a subset of participants (n = 383) were analyzed to determine the relative abundances of KEGG Orthology groups.

LMI was positively associated with hip BMD at high altitude [β (95 % CI) = 0.005 (0.003,0.007), P < 0.05], whereas no significant association was observed with spine BMD. This correlation varied significantly by altitude (P_inter< 0.05). A similar positive relationship was observed between microbial diversity (Shannon index) and hip_BMD [hip: β (95 % CI) = 0.605 (0.165, 1.044), P < 0.05]. Compared to the HLMI group, LLMI participants exhibited greater microbial diversity (P < 0.05), higher Faecalibacteriums abundance, and lower levels of Prevotella copri (P< 0.05). Functional metagenomic analysis identified differential enrichment of microbial pathways, including riboflavin metabolism, terpenoid backbone biosynthesis, alanine, aspartate, and glutamate metabolism (P < 0.05).

These findings highlight the correlation between LMI and hip BMD among high-altitude Tibetan adults, offering a potential mechanism for the interplay between GM profiles and bone health in high-altitude populations.