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; Hong Wen Deng

doi:10.1038/s41467-023-42005-y

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 SuXiang 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, Hong Wen Deng

Neuroscience and Regenerative Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	6853
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-42005-y
State	Published - Dec 2023

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Lin, X., Xiao, H. M., Liu, H. M., Lv, W. Q., Greenbaum, J., Gong, R., Zhang, Q., Chen, Y. C., Peng, C., Xu, X. J., Pan, D. Y., Chen, Z., Li, Z. F., Zhou, R., Wang, X. F., Lu, J. M., Ao, Z. X., Song, Y. Q., Zhang, Y. H., ... Deng, H. W. (2023). Gut microbiota impacts bone via Bacteroides vulgatus-valeric acid-related pathways. Nature communications, 14(1), Article 6853. https://doi.org/10.1038/s41467-023-42005-y

Lin, X, Xiao, HM, Liu, HM, Lv, WQ, Greenbaum, J, Gong, R, Zhang, Q, Chen, YC, Peng, C, Xu, XJ, Pan, DY, Chen, Z, Li, ZF, Zhou, R, Wang, XF, Lu, JM, Ao, ZX, Song, YQ, Zhang, YH, Su, KJ, Meng, XH, Ge, CL, Lv, FY, Luo, Z, Shi, XM, Zhao, Q, Guo, BY, Yi, NJ, Shen, H, Papasian, CJ, Shen, J & Deng, HW 2023, 'Gut microbiota impacts bone via Bacteroides vulgatus-valeric acid-related pathways', Nature communications, vol. 14, no. 1, 6853. https://doi.org/10.1038/s41467-023-42005-y

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title = "Gut microbiota impacts bone via Bacteroides vulgatus-valeric acid-related pathways",

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.",

author = "Xu Lin and Xiao, {Hong Mei} and Liu, {Hui Min} and Lv, {Wan Qiang} and Jonathan Greenbaum and Rui Gong and Qiang Zhang and Chen, {Yuan Cheng} and Cheng Peng and Xu, {Xue Juan} and Pan, {Dao Yan} and Zhi Chen and Li, {Zhang Fang} and Rou Zhou and Wang, {Xia Fang} and Lu, {Jun Min} and Ao, {Zeng Xin} and Song, {Yu Qian} and Zhang, {Yin Hua} and Su, {Kuan Jui} and Meng, {Xiang He} and Ge, {Chang Li} and Lv, {Feng Ye} and Zhe Luo and Shi, {Xing Ming} and Qi Zhao and Guo, {Bo Yi} and Yi, {Neng Jun} and Hui Shen and Papasian, {Christopher J.} and Jie Shen and Deng, {Hong Wen}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-42005-y",

language = "English (US)",

volume = "14",

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AU - Lin, Xu

AU - Xiao, Hong Mei

AU - Liu, Hui Min

AU - Lv, Wan Qiang

AU - Greenbaum, Jonathan

AU - Gong, Rui

AU - Zhang, Qiang

AU - Chen, Yuan Cheng

AU - Peng, Cheng

AU - Xu, Xue Juan

AU - Pan, Dao Yan

AU - Chen, Zhi

AU - Li, Zhang Fang

AU - Zhou, Rou

AU - Wang, Xia Fang

AU - Lu, Jun Min

AU - Ao, Zeng Xin

AU - Song, Yu Qian

AU - Zhang, Yin Hua

AU - Su, Kuan Jui

AU - Meng, Xiang He

AU - Ge, Chang Li

AU - Lv, Feng Ye

AU - Luo, Zhe

AU - Shi, Xing Ming

AU - Zhao, Qi

AU - Guo, Bo Yi

AU - Yi, Neng Jun

AU - Shen, Hui

AU - Papasian, Christopher J.

AU - Shen, Jie

AU - Deng, Hong Wen

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

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ER -

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

Abstract

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