Commensal Gut Microbiota Immunomodulatory Actions in Bone Marrow and Liver have Catabolic Effects on Skeletal Homeostasis in Health

摘要: Despite knowledge the gut microbiota regulates bone mass, mechanisms governing normal microbiota’s osteoimmunomodulatory effects on skeletal remodeling and homeostasis are unclear in healthy adult skeleton. Young specific-pathogen-free germ-free mice were used to delineate commensal immunoregulatory osteoblastogenesis, osteoclastogenesis, marrow T-cell hematopoiesis, extra-skeletal endocrine organ function. We report has anti-anabolic suppressing osteoblastogenesis pro-catabolic enhancing which drive loss health. Suppression of Sp7(Osterix) Igf1 bone, serum IGF1, suggest anti-osteoblastic actions mediated via local disruption IGF1-signaling. Differences RANKL/OPG Axis vivo, RANKL-induced maturation osteoclast-precursors vitro, indicate induces sustained changes RANKL-mediated osteoclastogenesis. Candidate mediating pro-osteoclastic include altered effector CD4+T-cells a novel Gut-Liver-Bone Axis. The previously unidentified intriguingly implies partly immunostimulatory liver. molecular underpinnings defining immunomodulatory physiologic highly relevant advancing understanding osteoimmunological processes, having implications for prevention deterioration health disease.