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Gut Microbiota Dysbiosis as One Cause of Osteoporosis by Impairing Intestinal Barrier Function

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Abstract

Gut microbiota (GM) dysbiosis is closely related to several metabolic diseases such as hypertension, obesity, and Alzheimer’s disease. However, little is known about the causal relationship between GM dysbiosis and osteoporosis. In our work, 32 3-month-old female SD rats were randomly divided into two groups: the fecal microbiota transplantation (FMT) group and the control group. The supernatant of feces from senile osteoporotic rats was transplanted to the FMT group and the same amount of sterile saline was given to the control rats. After 12 and 24 weeks, all rats were sacrificed, and the serum, bone, fecal feces, and intestine tissue were collected for the subsequent analysis. The osteocalcin (OC), CTX, and P1NP of the FMT group increased significantly at 12 and 24 weeks compared with the control group (P < 0.05). Furthermore, the BV, BV/TV, Tb.N, and Tb.Th decreased significantly in the FMT group (P < 0.05). The alpha diversity (ACE, Chao) of the FMT group was higher than the control at 24 weeks (P < 0.05). The beta diversity was close between the FMT rats and the donor rats. In addition, GM from donor rats changed the GM composition and function of the FMT rats, which was similar to that of the donor rats at 24 weeks. The impaired intestinal structure and the decreased expression of occludin, claudin, and ZO-1 were found in FMT rats. In conclusion, GM dysbiosis by transferring the feces from senile osteoporotic rats to young rats could induce osteoporosis. The changed GM and the impaired intestinal barrier contributed to the pathogenesis of osteoporosis.

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Acknowledgements

This study was supported by National Natural Science Foundation of China (Grant No. 82172456), the Cross-disciplinary Fund Projects of the Ninth People’s Hospital (Grant No. JYJC201809), Seeds Fund of Engineering Research Center of Digital Medicine of the Ministry of Education (Grant No. 20210407), Shanghai Clinical Medical Center (Grant No. 2017ZZ01023) and Shanghai Municipal Key Clinical Specialty.

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  1. Ning Wang and Sicong Ma have contributed equally to this work.

Authors and Affiliations

  1. Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, People’s Republic of China

    Ning Wang, Sicong Ma & Lingjie Fu

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  1. Ning Wang
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  2. Sicong Ma
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  3. Lingjie Fu
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Contributions

LF designed the experiments and supervised the project. SM performed the experiments and acquired the data. SM and NW analyzed the data. NW wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Lingjie Fu.

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Ning Wang, Sicong Ma, and Lingjie Fu declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

The use of animals in this study was approved by the Animal Care and Use Committee of Shanghai Ninth People’s Hospital. All applicable institutional and/or national guidelines for the care and use of animals were followed.

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Wang, N., Ma, S. & Fu, L. Gut Microbiota Dysbiosis as One Cause of Osteoporosis by Impairing Intestinal Barrier Function. Calcif Tissue Int 110, 225–235 (2022). https://doi.org/10.1007/s00223-021-00911-7

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