Amuc_1473 Links Gut Microbes to Skeletal Homeostasis and Counteracts Multifactorial Osteoporosis
ABSTRACT Emerging evidence suggests that gut microbiota‐derived signals can influence distant organs including the skeleton, yet the key microbial effectors remain elusive. Here, we identify Amuc_1473, a previously uncharacterized protein enriched in extracellular vesicles (EVs) from the commensal bacterium Akkermansia muciniphila ( Akk ), as a critical mediator of gut–bone communication. Amuc_1473 directly promotes osteogenesis and suppresses osteoclastogenesis by binding to negative elongation factor E (NELF‐E) and ribosomal protein L26 (RPL26), regulators of transcriptional pausing and mRNA translation, respectively. Notably, Amuc_1473 levels decline in bone and circulation under diverse pro‐osteoporotic conditions—including aging, estrogen deficiency, mechanical unloading, high‐fat diet, smoking, alcohol, and chronic stress—paralleling reductions in Akk and its EVs. Intermittent fasting robustly restores Akk abundance, Amuc_1473 levels, and bone quality in these models, via enhanced mucin production. Our findings establish Amuc_1473 as a microbial effector that systemically regulates bone homeostasis, offering a translatable strategy to prevent or treat multifactorial osteoporosis.
Authors
- Tengfei Wan (ORCID: https://orcid.org/0000-0002-0273-3721)
- Xin‐Yue Hu (ORCID: https://orcid.org/0000-0002-5588-9607)
- Hong-ji Liu
- J T Liu
- Jun Luo (ORCID: https://orcid.org/0000-0003-3339-5566)
- Chun‐Yuan Chen (ORCID: https://orcid.org/0000-0001-7808-533X)
- Yi Luo (ORCID: https://orcid.org/0000-0003-0007-0394)
- Jia Cao (ORCID: https://orcid.org/0000-0002-9508-1397)
- Shan‐Shan Rao
- Mingjie Luo (ORCID: https://orcid.org/0000-0001-6261-1024)
- Zi Wang (ORCID: https://orcid.org/0000-0002-3953-0493)
- Hui Xie (ORCID: https://orcid.org/0000-0002-8526-2637)
- Liu Y (ORCID: https://orcid.org/0009-0004-3901-1652)
- Hai‐Jin Zeng
- Yong Zhou (ORCID: https://orcid.org/0000-0003-3309-2565)
- Chun‐Gu Hong
- Yi‐Juan Tan (ORCID: https://orcid.org/0000-0001-5627-1860)
- Zehui He (ORCID: https://orcid.org/0000-0001-9339-8350)
- SW Cheng
- Du W
- Ying Duan (ORCID: https://orcid.org/0009-0007-0256-6058)
- Zun Wang
- Guo-Wen Hu
- Hai-Li Lang
- Hao Yin
- Peng Chen
- Xin Wang
- Zhe Guan
Institutions
- Central South University (CN)
- Nanchang University (CN)
- Xinjiang Medical University (CN)
- Second Affiliated Hospital of Nanchang University (CN)
- National Clinical Research (US)
- First Affiliated Hospital of University of South China (CN)
- Third Xiangya Hospital (CN)
- Xiangya Hospital Central South University (CN)
- University of South China (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2026-06-13
- DOI
- https://doi.org/10.1002/advs.202523067
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.00