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他汀类药物治疗对肠道微生物群的改变及其对高血糖和高脂血症可能的中间作用。

Alterations in Gut Microbiota by Statin Therapy and Possible Intermediate Effects on Hyperglycemia and Hyperlipidemia.

作者信息

Kim Jiyeon, Lee Heetae, An Jinho, Song Youngcheon, Lee Chong-Kil, Kim Kyungjae, Kong Hyunseok

机构信息

College of Pharmacy, Sahmyook University, Seoul, South Korea.

College of Pharmacy, Chungbuk National University, Cheongju, South Korea.

出版信息

Front Microbiol. 2019 Sep 4;10:1947. doi: 10.3389/fmicb.2019.01947. eCollection 2019.

Abstract

Dysbiosis of the gut microbiota is a contributing factor for obesity-related metabolic diseases such as hyperglycemia and hyperlipidemia. Pharmacotherapy for metabolic diseases involves the modulation of gut microbiota, which is suggested to be a potential therapeutic target. In this study, the modulation of gut microbiota by statins (cholesterol-lowering drugs: atorvastatin and rosuvastatin) was investigated in an aged mouse model of high-fat diet-induced obesity, and the association between gut microbiota and immune responses was described. Atorvastatin and rosuvastatin significantly increased the abundance of the genera , , and Moreover, the abundance of these genera was correlated with the inflammatory response, including levels of IL-1β and TGFβ1 in the ileum. In addition, oral fecal microbiota transplantation with fecal material collected from rosuvastatin-treated mouse groups improved hyperglycemia. From these results, the effect of statins on metabolic improvements could be explained by altered gut microbiota. Our findings suggest that the modulation of gut microbiota by statins has an important role in the therapeutic actions of these drugs.

摘要

肠道微生物群失调是肥胖相关代谢疾病(如高血糖和高血脂)的一个促成因素。代谢疾病的药物治疗涉及肠道微生物群的调节,这被认为是一个潜在的治疗靶点。在本研究中,在高脂饮食诱导肥胖的老年小鼠模型中研究了他汀类药物(降胆固醇药物:阿托伐他汀和瑞舒伐他汀)对肠道微生物群的调节作用,并描述了肠道微生物群与免疫反应之间的关联。阿托伐他汀和瑞舒伐他汀显著增加了 、 和 属的丰度。此外,这些属的丰度与炎症反应相关,包括回肠中白细胞介素-1β和转化生长因子β1的水平。此外,用从瑞舒伐他汀治疗的小鼠组收集的粪便材料进行口服粪便微生物群移植可改善高血糖。从这些结果来看,他汀类药物对代谢改善的作用可以通过肠道微生物群的改变来解释。我们的研究结果表明,他汀类药物对肠道微生物群的调节在这些药物的治疗作用中具有重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d63c/6736992/1aae9345711f/fmicb-10-01947-g001.jpg

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