GUT MICROBIOTA SIGNATURES AND CLINICAL CORRELATES IN OSTEOPOROSIS: A RETROSPECTIVE CASE-CONTROL STUDY

This retrospective case-control study investigated clinical correlates and gut microbiota signatures associated with reduced bone mineral density (BMD) through the gut-bone axis, a concept describing microbiota-related regulation of bone remodeling through immune, metabolic, intestinal barrier, and endocrine pathways. Using retrospective criterion-based sampling, eligible records from adults undergoing BMD testing and health screening between January 2024 and January 2025 were selected according to predefined criteria, yielding 60 participants with osteoporosis, 60 with osteopenia, and 58 controls. Clinical indicators, fasting blood markers, stool 16S ribosomal RNA (16S rRNA) sequencing profiles, differential taxa, predicted Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and correlations with BMD were compared among groups. Group comparisons used appropriate parametric, nonparametric, or chi-square ([Formula: see text]) tests; graphical and statistical presentations included principal coordinate analysis (PCoA), linear discriminant analysis effect size (LEfSe), Spearman correlation, and receiver operating characteristic (ROC) curves. Baseline characteristics were comparable (all [Formula: see text]), whereas BMD, inflammatory indices, bone-turnover markers, 25-hydroxyvitamin D, and selected cytokines differed significantly (all [Formula: see text]). Alpha diversity was similar among groups, but reduced bone status was associated with microbial dysbiosis, including a lower Firmicutes/Bacteroidetes ratio, decreased Megamonas, Agathobacter, and Faecalibacterium/Proteus ratio, and increased Escherichia and Aeromonas. LEfSe and predicted functional analyses identified disease-associated taxa and metabolic pathway shifts. Serum uric acid (SUA), erythrocyte sedimentation rate (ESR), and alkaline phosphatase (ALP) correlated negatively with BMD (all [Formula: see text]), whereas transforming growth factor-[Formula: see text] (TGF-[Formula: see text]) correlated positively ([Formula: see text]). Osteoporosis was associated with gut microbial dysbiosis and altered inflammatory and metabolic profiles, supporting the gut-bone axis and providing targets for future validation.