A eubiotic microbiota influences many physiological processes in the metazoan host, including development and intestinal homeostasis. Here, we have shown that the intestinal microbiota modulates inflammatory responses caused by sex steroid deficiency, leading to trabecular bone loss. In murine models, sex steroid deficiency increased gut permeability, expanded Th17 cells, and upregulated the osteoclastogenic cytokines TNFα (TNF), RANKL, and IL-17 in the small intestine and the BM. In germ-free (GF) mice, sex steroid deficiency failed to increase osteoclastogenic cytokine production, stimulate bone resorption, and cause trabecular bone loss, demonstrating that the gut microbiota is central in sex steroid deficiency–induced trabecular bone loss. Furthermore, we demonstrated that twice-weekly treatment of sex steroid–deficient mice with the probiotics
Jau-Yi Li, Benoit Chassaing, Abdul Malik Tyagi, Chiara Vaccaro, Tao Luo, Jonathan Adams, Trevor M. Darby, M. Neale Weitzmann, Jennifer G. Mulle, Andrew T. Gewirtz, Rheinallt M. Jones, Roberto Pacifici
GF mice are protected against the loss of trabecular bone induced by sex steroid deficiency.
Assessment of femoral bone structure by in vitro μCT in Conv.R mice, GF mice, and Col.GF mice following either leuprolide (375 μg/month) or vehicle control treatment for 10 weeks. (