The Impact of Gut Microbiota on the Suppressive Property of Phytochemicals Derived From Medicinal Plants on Bone Loss via Induction of Osteoblast Differentiation

Abstract

Objectives: Osteoporosis is a metabolic skeletal disease characterized by bone loss and an increased risk of fractures. Recent studies have actively reported the correlation between osteoporosis and the gut microbiome. This study aimed to investigate the therapeutic effects of various phytochemicals on osteoporosis and discover the impact of microbiomes on their effects. ？ Methods: MC3T3-E1 mouse pre-osteoblasts were used in vitro study and 8-week-old ovariectomized (OVX) female C57BL/6J mice were used as an animal model with osteoporosis. To find critical microbiomes modulating bone health, 6 founder strain mice with bone damage by dexamethasone were utilized and ginsenoside Rg3 was administered to mice to select possible candidates from microbes. Demonstration of candidate microbes on bone health was verified by comparison between sensitive and resistant mice strains. ？ Results: Several medicinal plants and their compounds were found to have inducible activity on osteoblast differentiation both in vitro and in vivo, resulting in higher bone density in their treated mice than OVX mice. Simultaneously, those phytochemicals increased gut microbial diversity, and recovered the gut microbial alteration induced by ovariectomy. In 6 founder strain mice with dexamethasone and Rg3, two possible candidate microbes, Eubacterium nodatum and Eubacterium ventriosum were selected. Oral administration of candidate microbes restored the bone health damaged by dexamethasone. ？ Conclusions: Phytochemicals could be good agents for the treatment of osteoporosis and their partial effect might be mediated by modulation of gut microbiomes. Development of specific microbes having suppressive impact on osteoporosis could be a novel solution for bone as well as intestinal health.