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肠道微生物通过脆弱拟杆菌和乙酸加速绝经前后妇女的肥胖。

Gut microbiota accelerates obesity in peri-/post-menopausal women via Bacteroides fragilis and acetic acid.

机构信息

Center for System Biology, Data Sciences, and Reproductive Health, School of Basic Medical Science, Central South University, 172 Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, PR China.

Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, China.

出版信息

Int J Obes (Lond). 2022 Oct;46(10):1918-1924. doi: 10.1038/s41366-022-01137-9. Epub 2022 Aug 17.

Abstract

OBJECTIVE

Many animal experiments and epidemiological studies have shown that the gut microbiota (GM) plays an important role in the development of obesity, but the specific biological mechanism involved in the pathogenesis of disease remain unknown. We aimed to examine the relationships and functional mechanisms of GM on obesity in peri- and post-menopausal women.

METHODS

We recruited 499 Chinese peri- and post-menopausal women and performed comprehensive analyses of the gut microbiome, targeted metabolomics for short-chain fatty acids in serum, and host whole-genome sequencing by various association analysis methods.

RESULTS

Through constrained linear regression analysis, we found that an elevated abundance of Bacteroides fragilis (B. fragilis) was associated with obesity. We also found that serum levels of acetic acid were negatively associated with obesity, and that B. fragilis was negatively associated with serum acetic acid levels by partial Spearman correlation analysis. Mendelian randomization analysis indicated that B. fragilis increases the risk of obesity and may causally down-regulate acetic acid levels.

CONCLUSIONS

We found the gut with B. fragilis may accelerate obesity, in part, by suppressing acetic acid levels. Therefore, B. fragilis and acetic acid may represent important therapeutic targets for obesity intervention in peri- and post-menopausal women.

摘要

目的

许多动物实验和流行病学研究表明,肠道微生物群(GM)在肥胖的发展中起着重要作用,但疾病发病机制中涉及的具体生物学机制尚不清楚。我们旨在研究 GM 与绝经前后妇女肥胖的关系及其功能机制。

方法

我们招募了 499 名中国绝经前后妇女,并通过各种关联分析方法对肠道微生物组、血清短链脂肪酸的靶向代谢组学以及宿主全基因组测序进行了综合分析。

结果

通过约束线性回归分析,我们发现脆弱拟杆菌(Bacteroides fragilis,B. fragilis)丰度的升高与肥胖有关。我们还发现,血清乙酸水平与肥胖呈负相关,而通过部分 Spearman 相关分析,B. fragilis 与血清乙酸水平呈负相关。孟德尔随机化分析表明,B. fragilis 增加肥胖的风险,并可能通过下调乙酸水平导致肥胖。

结论

我们发现肠道中存在 B. fragilis 可能通过抑制乙酸水平加速肥胖的发生。因此,B. fragilis 和乙酸可能代表绝经前后妇女肥胖干预的重要治疗靶点。

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