Berberine Attenuates Glucocorticoid-Induced Bone Loss in Mice: Associated with the Gut Microbiota–Glycerophospholipid Metabolic Axis

Dietary supplementation with functional nutrients is a safe strategy to improve bone health. This study aimed to investigate the ameliorative effects of Berberine (BBR) on dexamethasone-induced bone loss in mice and its potential mechanisms. Micro-CT, histological staining, ELISA and Western blot were employed to evaluate BBR’s skeletal benefits; 16S rRNA sequencing, serum metabolomics and correlation analysis were used to explore its regulatory mechanisms. In vivo experiments showed that BBR improved bone mineral density and trabecular microarchitecture, and upregulated osteogenic markers (COL1 and BMP2). Intestinal bacterial sequencing showed that BBR altered gut bacterial composition, increasing the abundance of Desulfovibrio and Bacteroides while decreasing opportunistic pathogens. BBR also modulated bacterial richness, evenness, and community stability. Serum metabolomics identified 107 BBR-reversed differential metabolites; of these, 33.64% were lipids and lipid-like molecules, which were mainly involved in glycerophospholipid metabolism. Further correlation analysis revealed that BBR-enriched Desulfovibrio was linked to pathway R04864, producing a key glycerophospholipid metabolite positively correlated with bone mass parameters. Overall, these findings suggest that the attenuation of bone loss by BBR may be associated with alterations in the gut microbiota–glycerophospholipid metabolic axis, supporting its potential as a functional food ingredient for bone health.