Selenium‐Enriched Egg White Protein Alleviates Glucocorticoid‐Induced Osteoporosis Mice via Gut Microbiota‐Driven Htr1b Inhibition

Long‐term glucocorticoid therapy is known to induce osteoporosis by disrupting bone metabolism and altering gut microbiota. In this study, C57BL/6J mice were used to establish a glucocorticoid‐induced osteoporosis (GIOP) model by intramuscular injection of dexamethasone. The mice were then divided into control, GIOP, and experimental groups; the experimental group was orally administered selenium‐enriched egg white protein (Se‐EWP) in order to evaluate its bone‐protective effects and potential mechanisms. The results showed that Se‐EWP significantly improved bone strength, trabecular microstructure, and bone mineral density in GIOP mice; enhanced the expression of bone synthesis‐related proteins, such as osterix and osteocalcin; and decreased the expression of bone catabolism‐related proteins, such as tartrate‐resistant acid phosphatase, receptor activator of nuclear factor‐κB ligand, and cathepsin K. In addition, Se‐EWP was found to alleviate glucocorticoid‐induced gut microflora dysbiosis by increasing beneficial bacteria and microbial diversity. Se‐EWP significantly modulated the 5‐hydroxytryptamine receptor 1B (Htr1b) pathway, which is crucial for bone homeostasis and gut–bone communication. The modulation of the Htr1b pathway suggests that Se‐EWP may exert its anti‐osteoporotic effects through this mechanism. These effects were statistically significant ( p < 0.05). Correlation analysis revealed significant associations between changes in the intestinal microbiota and bone metabolism parameters, further supporting the hypothesis that Se‐EWP exerts its effects through the gut–bone axis. This suggests a novel therapeutic mechanism of action for Se‐EWP through the gut–bone axis. In conclusion, this study provides strong evidence supporting the application of Se‐EWP in the prevention and treatment of GIOP.