Gut microbiota impacts bone via Bacteroides vulgatus-valeric acid-related pathways

Xu Lin, Hong-Mei Xiao (), Hui-Min Liu, Wan-Qiang Lv, Jonathan Greenbaum, Rui Gong, Qiang Zhang, Yuan-Cheng Chen, Cheng Peng, Xue-Juan Xu, Dao-Yan Pan, Zhi Chen, Zhang-Fang Li, Rou Zhou, Xia-Fang Wang, Jun-Min Lu, Zeng-Xin Ao, Yu-Qian Song, Yin-Hua Zhang, Kuan-Jui Su, Xiang-He Meng, Chang-Li Ge, Feng-Ye Lv, Zhe Luo, Xing-Ming Shi, Qi Zhao, Bo-Yi Guo, Neng-Jun Yi, Hui Shen, Christopher J. Papasian, Jie Shen () and Hong-Wen Deng ()
Additional contact information
Xu Lin: Shunde Hospital of Southern Medical University (The First People’s Hospital of Shunde)
Hong-Mei Xiao: Central South University
Hui-Min Liu: Central South University
Wan-Qiang Lv: Central South University
Jonathan Greenbaum: Tulane University
Rui Gong: The Third Affiliated Hospital of Southern Medical University
Qiang Zhang: Tulane University
Yuan-Cheng Chen: The Third Affiliated Hospital of Southern Medical University
Cheng Peng: The Third Affiliated Hospital of Southern Medical University
Xue-Juan Xu: The Third Affiliated Hospital of Southern Medical University
Dao-Yan Pan: The Third Affiliated Hospital of Southern Medical University
Zhi Chen: The Third Affiliated Hospital of Southern Medical University
Zhang-Fang Li: The Third Affiliated Hospital of Southern Medical University
Rou Zhou: The Third Affiliated Hospital of Southern Medical University
Xia-Fang Wang: The Third Affiliated Hospital of Southern Medical University
Jun-Min Lu: The Third Affiliated Hospital of Southern Medical University
Zeng-Xin Ao: The Third Affiliated Hospital of Southern Medical University
Yu-Qian Song: The Third Affiliated Hospital of Southern Medical University
Yin-Hua Zhang: The Third Affiliated Hospital of Southern Medical University
Kuan-Jui Su: Tulane University
Xiang-He Meng: Tulane University
Chang-Li Ge: LC-Bio Technologies (Hangzhou) CO., LTD.
Feng-Ye Lv: LC-Bio Technologies (Hangzhou) CO., LTD.
Zhe Luo: Tulane University
Xing-Ming Shi: Augusta University
Qi Zhao: University of Tennessee Health Science Center
Bo-Yi Guo: University of Alabama at Birmingham
Neng-Jun Yi: University of Alabama at Birmingham
Hui Shen: Tulane University
Christopher J. Papasian: University of Missouri-Kansas City
Jie Shen: Shunde Hospital of Southern Medical University (The First People’s Hospital of Shunde)
Hong-Wen Deng: Tulane University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-42005-y

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