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绝经后骨质疏松症小鼠模型的粪便和血清代谢组学特征及微生物群落分析。

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

机构信息

Department of Orthopaedics, First Affiliated Hospital of China Medical University, Shenyang, China.

Department of Orthopaedics, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Front Cell Infect Microbiol. 2020 Nov 27;10:535310. doi: 10.3389/fcimb.2020.535310. eCollection 2020.

Abstract

BACKGROUND

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. We explored the effect of the intestinal microbiota on osteoporosis.

METHODS

We 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.

RESULTS

We 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.

CONCLUSIONS

These 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.

摘要

背景

多项研究表明,肠道微生物群失衡与骨代谢有关,但肠道微生物群在绝经后骨质疏松症中的作用仍需阐明。我们探讨了肠道微生物群对骨质疏松症的影响。

方法

构建绝经后骨质疏松症小鼠模型,采用 Micro CT 观察骨结构变化。然后,通过 16S RNA 测序鉴定肠道微生物群的丰度,发现厚壁菌门和拟杆菌门的比例显著增加。进一步采用 UHPLC-MS 分析粪便和血清中代谢物的变化。

结果

在 OP 条件下,我们在粪便中鉴定出 53 个上调和 61 个下调代谢物,在血清中鉴定出 2 个上调和 22 个下调代谢物,有趣的是,一组胆汁酸在 OP 和对照组之间表现出显著差异。网络分析还发现,这些胆汁酸与 Eggerthellaceae 家族有很强的关系。随机森林分析证实了血清和粪便模型在区分 OP 组和对照组方面的有效性。

结论

这些结果表明,粪便中肠道微生物群和代谢物的变化导致了绝经后骨质疏松症的发生和发展。肠道微生物群是骨质疏松症的重要诱导因素,可通过“微生物群-肠道-代谢物-骨骼”轴调节发病机制,该轴的一些成分是潜在的生物标志物,为绝经后骨质疏松症发病机制的未来研究提供了新的切入点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e15e/7728697/89e61730c3c7/fcimb-10-535310-g001.jpg

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