Lactobacillus plantarum attenuates glucocorticoid-induced osteoporosis by altering the composition of rat gut microbiota and serum metabolic profile

Osteoporosis, one of the most common non-communicable human diseases worldwide, is one of the most prevalent disease of the adult skeleton. Glucocorticoid-induced osteoporosis(GIOP) is the foremost form of secondary osteoporosis, extensively researched due to its prevalence.Probiotics constitute a primary bioactive component within numerous foods, offering promise as a potential biological intervention for preventing and treating osteoporosis. This study aimed to evaluate the beneficial effects of the probiotic on bone health and its underlying mechanisms in a rat model of glucocorticoid dexamethasone-induced osteoporosis, using the osteoporosis treatment drug alendronate as a reference. We examined the bone microstructure (Micro-CT and HE staining) and analyzed the gut microbiome and serum metabolome in rats. The results revealed that treatment significantly restored parameters of bone microstructure, with elevated bone density, increased number and thickness of trabeculae, and decreased Tb.Sp. Gut microbiota sequencing results showed that probiotic treatment increased gut microbial diversity and the ratio of Firmicutes to Bacteroidota decreased. Beneficial bacteria abundance was significantly increased ( _NK4A136_group, , , , and _R_7_group), and harmful bacteria abundance was significantly decreased ( ). According to the results of serum metabolomics, significant changes in serum metabolites occurred in different groups. These differential metabolites were predominantly enriched within the pathways of Pentose and Glucuronate Interconversions, as well as Propanoate Metabolism. Furthermore, treatment of significantly increased serum levels of Pyrazine and gamma-Glutamylcysteine, which were associated with inhibition of osteoclast formation and promoting osteoblast formation. can protect rats from DEX-induced GIOP by mediating the "gut microbial-bone axis" promoting the production of beneficial bacteria and metabolites. Therefore is a potential candidate for the treatment of GIOP.