Gut microbiota impacts bone via Bacteroides vulgatus-valeric acid-related pathways
Xu Lin, Hong‐Mei Xiao, Hui Li, Wan‐Qiang Lv, Jonathan Greenbaum, Rui Gong, Qıang Zhang, Yuancheng Chen, Cheng Peng, Xuejuan Xu, Dao-Yan Pan, Z. Chen, Zhang-Fang Li, Rou Zhou, Xia-Fang Wang, Jun‐Min Lu, Zeng‐Xin Ao, Yu-Qian Song, Yinhua Zhang, Kuan‐Jui Su, Xiang‐He Meng, Chang-Li Ge, Feng-Ye Lv, Zhe Luo, Xingming Shi, Qi Zhao, Boyi Guo, Nengjun Yi, Hui Shen, Christopher J. Papasian, Jie Shen, Hong‐Wen Deng
Abstract
Although the gut microbiota has been reported to influence osteoporosis risk, the individual species involved, and underlying mechanisms, remain largely unknown. We performed integrative analyses in a Chinese cohort of peri-/post-menopausal women with metagenomics/targeted metabolomics/whole-genome sequencing to identify novel microbiome-related biomarkers for bone health. Bacteroides vulgatus was found to be negatively associated with bone mineral density (BMD), which was validated in US white people. Serum valeric acid (VA), a microbiota derived metabolite, was positively associated with BMD and causally downregulated by B. vulgatus. Ovariectomized mice fed B. vulgatus demonstrated increased bone resorption and poorer bone micro-structure, while those fed VA demonstrated reduced bone resorption and better bone micro-structure. VA suppressed RELA protein production (pro-inflammatory), and enhanced IL10 mRNA expression (anti-inflammatory), leading to suppressed maturation of osteoclast-like cells and enhanced maturation of osteoblasts in vitro. The findings suggest that B. vulgatus and VA may represent promising targets for osteoporosis prevention/treatment.