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journal article·2026-06-13Open access

Amuc_1473 Links Gut Microbes to Skeletal Homeostasis and Counteracts Multifactorial Osteoporosis

Shan‐Shan Rao, Hai‐Jin Zeng, Zun Wang, Chun‐Gu Hong, Yi‐Juan Tan, Yan‐Xin Duan, Jing‐Yao Luo, Ming‐Jie Luo, Yi‐Wei Liu, Xin Wang, Yi Luo, Teng‐Fei Wan, Yong Zhou, Zheng‐Guang Wang, Guo‐Wen Hu, Hao Yin, Xin‐Yue Hu, Zhen‐Xing Wang, Ze‐Hui He, Si‐Yi Cheng, Wei Du, Zhe Guan, Hai‐Li Lang, Hong‐Ji Liu, Jia Cao, Peng Chen, Jiang‐Hua Liu, Hui Xie, Chun‐Yuan Chen

Advanced Science
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Abstract

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.
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Research context

OpenAlex topics: Gut microbiota and health · Bone Metabolism and Diseases · Oral microbiology and periodontitis research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Orthopedics Movement System Injury and Repair Research Center Xiangya Hospital Central South University Changsha Hunan China

Hunan Key Laboratory of Angmedicine Changsha Hunan China

National Clinical Research Center For Geriatric Disorders Xiangya Hospital Central South University Changsha Hunan China

Experimental Center of Nursing School Xinjiang Medical University Urumqi Xinjiang China

Department of Orthopaedics The Third Xiangya Hospital Central South University Changsha Hunan China

Department of Neurosurgery The Second Affiliated Hospital of Nanchang University Nanchang Jiangxi China

Department of Respiratory Medicine Xiangya Hospital Central South University Changsha Hunan China

Department of P.E Central South University Changsha Hunan China

Department of Rehabilitation Xiangya Hospital Central South University Changsha Hunan China

Department of Anesthesiology The Second Affiliated Hospital of Nanchang University Nanchang Jiangxi China

Department of Orthopaedics the First Affiliated Hospital Hengyang Medical School University of South China Hengyang China

FuRong Laboratory Changsha Hunan China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Hunan Province · China Postdoctoral Science Foundation

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