Fecal and Serum Metabolomic Signatures and Microbial Community Profiling of Postmenopausal Osteoporosis Mice Model.

Kaicheng Wen,Jianhua Chen,Yan Meng,Siming Zhou,Zhengbo Tao,Wacili Da,Lin Tao,Yue Zhu,Keda Yang

doi:10.3389/fcimb.2020.535310

Kaicheng Wen, Jianhua Chen + Show 7 more

Open Access

https://doi.org/10.3389/fcimb.2020.535310

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Abstract

BackgroundMultiple studies have shown that an imbalance in the intestinal microbiota is related to bone metabolism, but the role of the intestinal microbiota in postmenopausal osteoporosis remains to be elucidated. We explored the effect of the intestinal microbiota on osteoporosis.MethodsWe constructed a postmenopausal osteoporosis mouse model, and Micro CT was used to observe changes in bone structure. Then, we identified the abundance of intestinal microbiota by 16S RNA sequencing and found that the ratio of Firmicutes and Bacteroidetes increased significantly. UHPLC-MS analysis was further used to analyze changes in metabolites in feces and serum.ResultsWe identified 53 upregulated and 61 downregulated metabolites in feces and 2 upregulated and 22 downregulated metabolites in serum under OP conditions, and interestedly, one group of bile acids showed significant differences in the OP and control groups. Network analysis also found that these bile acids had a strong relationship with the same family, Eggerthellaceae. Random forest analysis confirmed the effectiveness of the serum and fecal models in distinguishing the OP group from the control group.ConclusionsThese results indicated that changes in the gut microbiota and metabolites in feces and serum were responsible for the occurrence and development of postmenopausal osteoporosis. The gut microbiota is a vital inducer of osteoporosis and could regulate the pathogenesis process through the “microbiota-gut-metabolite-bone” axis, and some components of this axis are potential biomarkers, providing a new entry point for the future study on the pathogenesis of postmenopausal osteoporosis.

Highlights

Postmenopausal osteoporosis (OP), the most common type of primary osteoporosis, poses a large threat to the health of women around the world (Watts et al, 2010; Pagnotti et al, 2019)
After feeding for one week under this condition, we randomly divided the mice into a postmenopausal osteoporosis group and a control group, with seven mice in each group, and performed ovariectomy on the mice in the OP group to construct postmenopausal osteoporosis models
To clarify how the intestinal flora regulates bone metabolism, we further explored the metabolism of postmenopausal osteoporosis to determine the pathogenic mechanism of OP

Summary

Introduction

Postmenopausal osteoporosis (OP), the most common type of primary osteoporosis, poses a large threat to the health of women around the world (Watts et al, 2010; Pagnotti et al, 2019). Postmenopausal osteoporosis is a systemic metabolic disease (Black and Rosen, 2016b), and the relationship with gut microbiota remains to be further explored. When the intestinal microbiota was recolonized, both trabecular density and cortical cross-sectional area were decreased, indicating that the intestinal microbiota is closely related to bone metabolism (Li et al, 2016). The intestinal microbiota may affect bone metabolism through the immune system, endocrine system, or ion absorption (Gilman and Cashman, 2006; Sjogren et al, 2012; Yan et al, 2016), and either pathway is closely related to the concentration of various metabolites in the blood and intestines. Multiple studies have shown that an imbalance in the intestinal microbiota is related to bone metabolism, but the role of the intestinal microbiota in postmenopausal osteoporosis remains to be elucidated.

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