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Cited by 101Gut microbiota and healthBone health and osteoporosis researchBone Metabolism and Diseases

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

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Lin, Xu, Xiao, Hong-Mei, Liu, Hui-Min, Lv, Wan-Qiang, Greenbaum, Jonathan, Gong, Rui, Zhang, Qiang, Chen, Yuan-Cheng +24 more·2023·Nature Communications
DOI 10.1038/s41467-023-42005-yPMC PMC10611739
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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.

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Crossref · 10.1038/s41467-023-42005-y

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  • B. vulgatus accelerates bone resorption and compromises bone microarchitecture, whereas valeric acid inhibits osteoclast maturation and enhances osteoblast differentiation.

    “B. vulgatus accelerates bone resorption and compromises bone microarchitecture, whereas valeric acid inhibits osteoclast maturation and enhances osteoblast differentiation [61]”

    From Interorgan Communications in Skeletal Pathophysiology: From Molecular Pathways to Multidisciplinary Therapies (2026) · cites this paper as [61]

    The Results (In vivo and in vitro validation; page not provided) say B. vulgatus promoted bone resorption and deteriorated bone architecture in ovariectomized mice, but explicitly state that these effects were not detected in sham mice. The same section reports that valeric acid inhibited osteoclast-like cell differentiation and increased osteoblast differentiation in vitro. The citing sentence omits the mouse-model condition on the B. vulgatus finding. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • In peri- and postmenopausal women, Bacteroides vulgatus is inversely associated with BMD, while valeric acid correlates positively with BMD.

    “Bacteroides vulgatus is inversely associated with bone mineral density (BMD), while the SCFA-related metabolite valeric acid correlates positively with BMD.”

    From Interorgan Communications in Skeletal Pathophysiology: From Molecular Pathways to Multidisciplinary Therapies (2026) · cites this paper as [61]

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Cited by

Sorted by citations

Authors
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., Su, K.-J., Meng, X.-H., Ge, C.-L., Lv, F.-Y., Luo, Z., Shi, X.-M., Zhao, Q., Guo, B.-Y., Yi, N.-J., Shen, H., Papasian, C. J., Shen, J., & Deng, H.-W.
Affiliations
  • Third Affiliated Hospital of Southern Medical University (CN)
  • Central South University (CN)
  • Tulane University (US)
  • University of Tennessee Health Science Center (US)
  • University of Missouri–Kansas City (US)
Corresponding author
  • Xiao, Hong-Mei
  • Shen, Jie
  • Deng, Hong-Wen
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2023-10-27
Volume
14
Issue
1
Pages
6853-6853
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-023-42005-y
PMC
PMC10611739
OpenAlex
W4387996586
Cited by
101
References
7
Citations by year
2026: 35 · 2025: 40 · 2024: 22 · 2023: 2 · 2022: 2
FWCI
8.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Tulane University (P20 GM109036, R01AR069055, R01MH104680)
  • National Natural Science Foundation of China (81770878, 2017YFC1001100, R01MH104680)
  • Southern Medical University
  • National Institutes of Health (U19AG05537301)
  • National Institute on Aging (R01AG061917, U19AG055373)
  • National Institute of Mental Health (R01MH104680)
  • National Institute of General Medical Sciences (P20GM109036)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR069055)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Keywords
gut microbiota, Bacteroides vulgatus, valeric acid, osteoporosis, bone mineral density, bone resorption, bone microarchitecture, menopausal women, ovariectomy, osteoclastogenesis, osteogenic differentiation, RelA, IL-10, gut microbiota metabolites, bone health biomarkers
MeSH terms
Gastrointestinal Microbiome, Animals, Bacteroides, Bone Resorption, Female, Humans, Osteoporosis, Pentanoic Acids, Mice

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