Dietary patterns and osteoporosis risk in a high-altitude population: the roles of gut microbiota and plasma metabolites in a case-control study.

BACKGROUND: This study investigated the association between dietary pattern and osteoporosis, exploring gut microbiota and plasma metabolites as potential mediators. METHODS: This case-control study included 90 osteoporosis patients and 90 healthy controls. All participants completed a validated semi-quantitative food frequency questionnaire (FFQ) to assess their dietary intake over the past year. Principal component analysis (PCA) was performed on the FFQ data to identify major dietary patterns. Gut microbiota composition was analyzed using metagenomic sequencing (Illumina HiSeq platform, PE150). Plasma metabolites were analyzed using untargeted metabolomics with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Binary logistic regression was employed to examine the association between dietary pattern and osteoporosis; Multivariate linear regression was used to investigate the association between dietary pattern and gut microbiota/metabolites. Additionally, mediation analysis was conducted to assess whether gut microbiota or plasma metabolites mediated the association between dietary patterns and osteoporosis, and the proportion of mediation was calculated. RESULTS: The osteoporosis group showed significant differences in age (61.89 ± 7.86 vs. 56.10 ± 7.29 years), sex (72.2% vs. 36.7% female), and anthropometrics (all P < 0.05). Among six identified dietary patterns, "animal offal and seeds" was associated with higher osteoporosis risk (OR = 2.21, 1.21-4.06; P = 0.010). osteoporosis patients exhibited gut microbiota dysbiosis (enriched Enterobacteriaceae) and seven metabolites exerted mediating effects on the association between dietary pattern and osteoporosis. CONCLUSION: In high-altitude population, the "animal offal and seeds" dietary pattern elevates osteoporosis risk, partially mediated by metabolite. Gut microbiota composition also differs significantly between osteoporosis patients and controls.