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.