Androgen deficiency-induced loss of Lactobacillus salivarius extracellular vesicles is associated with the pathogenesis of osteoporosis

Male osteoporosis is primarily caused by a decrease in testicular testosterone production. Male osteoporosis remains a disease with insufficient diagnosis and treatment, and its consequences are severe, especially in older patients. The gut microbiota plays a crucial role in its occurrence and development. Our study found that the relative abundance of Lactobacillus salivarius in the fecal microbiota of male patients with osteoporosis was significantly lower than that in healthy volunteers. Animal experiments have shown that orchiectomy (ORX) can induce osteoporosis and disrupt the intestinal mucosal barrier, and intestinal microbiota. In addition, we discovered a potential etiological connection between the decreased abundance of the intestinal bacterium L. salivarius and the occurrence of ORX-induced osteoporosis. Cohousing or direct colonization of the intestinal microbiota from healthy rats or direct oral administration of the bacteria alleviated ORX-induced osteoporosis and repaired the intestinal mucosal barrier. Finally, we demonstrated that the extracellular vesicles (EVs) of L. salivarius could be transported to the bones and mitigate ORX-induced osteoporosis in rats. Our results indicate that the gut microbiota participates in protecting bones by secreting and delivering bacterial EVs, and that the reduction of L. salivarius and its EVs is closely related to the development of androgen deficiency-related osteoporosis.