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Neuropeptide Y1 Receptor Antagonist Alters Gut Microbiota and Alleviates the Ovariectomy-Induced Osteoporosis in Rats

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Abstract

A plethora of evidence has suggested that gut microbiota is involved in the occurrence and development of postmenopausal osteoporosis (PMO). It has been suggested that neuropeptide Y (NPY) modulates the bone metabolism through Y1 receptor (Y1R), and might be associated with gut microbiota. The present study aims to evaluate the anti-osteoporotic effects of Y1R antagonist and to investigate the potential mechanism by which Y1R antagonist regulates gut microbiota. In this study, eighteen female rats were randomly divided into three groups: the sham surgery (SHAM) group, the ovariectomized (OVX) group, and OVX+BIBO3304 group. After 6 weeks following surgery, Y1R antagonist BIBO3304 was administered to the rats in OVX+BIBO3304 group for 7 days. The bone microstructure and serum biochemical parameters were measured at 12 weeks after operation. The differences in the gut microbiota were analyzed by 16S rDNA gene sequencing. Heat-map and Spearman’s correlation analyses were constructed to investigate the correlations between microbiota and bone metabolism-related parameters. The results indicated that OVX+BIBO3304 group showed significantly higher BMD, BV/TV, Tb.Th, Tb.N, Conn.D, and serum Ca2+ level than those in OVX group. Additionally, Y1R antagonist changed the gut microbiota composition with lower Firmicutes/Bacteroidetes ratio and higher proportions of some probiotics, including Lactobacillus. The correlation analysis showed that the changes of gut microbiota were closely associated with bone microstructure and serum Ca2+ levels. Our results suggested that Y1R antagonist played an anti-osteoporotic effect and regulated gut microbiota in OVX rats, indicating the potential to utilize Y1R antagonist as a novel treatment for PMO.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China [Grant Nos. 81871090 and 81400904], Medical-Engineering Joint Fund of Shanghai Jiaotong University [YG2016MS53], and Clinical research and cultivation fund of Renji Hospital (PY2018-III-07).

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  1. Weixin Xie and Yi Han have contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 1630 Dongfang Rd, Shanghai, 200127, China

    Weixin Xie, Yi Han, Fan Li & Zhanchun Li

  2. Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 1630 Dongfang Rd, Shanghai, 200127, China

    Xiyao Gu, Diansan Su, Weifeng Yu & Jie Xiao

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  1. Weixin Xie
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Correspondence to Zhanchun Li or Jie Xiao.

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Weixin Xie, Yi Han, Fan Li, Xiyao Gu, Diansan Su, Weifeng Yu, Zhanchun Li, and Jie Xiao declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This study was ethically approved by the Institutional Animal Care and Use Committee of Shanghai Jiaotong University (RJ2018-1012) and was conducted in conformity with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.

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Jie Xiao is the corresponding author and Zhanchun Li is the co-corresponding author.

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223_2019_647_MOESM1_ESM.tif

Electronic supplementary material 1—Fig. S1 The PICRUSt analysis based on KEGG database between OVX group and SHAM group (TIF 4526 kb)

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Xie, W., Han, Y., Li, F. et al. Neuropeptide Y1 Receptor Antagonist Alters Gut Microbiota and Alleviates the Ovariectomy-Induced Osteoporosis in Rats. Calcif Tissue Int 106, 444–454 (2020). https://doi.org/10.1007/s00223-019-00647-5

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