The effect of canagliflozin on gut microbiota and metabolites in type 2 diabetic mice.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-05-01 Epub Date: 2024-03-14 DOI:10.1007/s13258-024-01491-0

Li Zeng, Jideng Ma, Tiantian Wei, Hao Wang, Guitao Yang, Chongxiang Han, Tao Zhu, Haoming Tian, Min Zhang

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引用次数: 0

Abstract

Background: Sodium glucose cotransporter 2 inhibitor (SGLT2i) represent a new type of hypoglycemic medicine that can cause massive loss of glucose from the urine, which have several benefits of reducing body weight and improving the prognosis of cardiovascular and kidney diseases. Although they are oral medicated hypoglycemic agents, their effects on the gut microbiome and function have been unclear.

Objective: In order to describe the effects of canagliflozin on intestinal flora and metabolites, diabetic mice were randomized to receive canagliflozin or isoconcentration carboxymethylcellulose sodium by gavage for 8 weeks. Feces were collected for 16 S rRNA gene and LC-MS/MS analysis and enriched metabolic pathways through Kyoto Encyclopedia of Genes and Genomes (KEGG). Liver, muscle, intestinal, fat were collected for qRT-PCR according to KEGG enriched metabolic pathways.

Results: Our results showed that canagliflozin significantly increased GLP-1 level and impacted on the composition of gut microbiota and metabolites. It mainly increased Muribaculum, Ruminococcaceae_UCG_014, Lachnospiraceae-UCG-001, decreased ursodeoxycholic acids (UDCA) and hyodeoxycholic acids (HDCA), and increased fatty acids metabolites in feces.

Conclusion: In conclusion, we analyzed the changes of intestinal microbial composition and metabolites in diabetic mice after canagliflozin intervention and found that canagliflozin influenced intestinal fatty acid and bile acid (BA) metabolism. This study will provide reference for subsequent SGLT2i and intestinal related research.

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卡格列净对 2 型糖尿病小鼠肠道微生物群和代谢物的影响

背景：葡萄糖钠共转运体2抑制剂（SGLT2i）是一种新型降糖药物，可使葡萄糖从尿液中大量流失，具有减轻体重、改善心血管疾病和肾脏疾病预后等多种益处。虽然它们是口服药物降糖药，但其对肠道微生物组和功能的影响尚不清楚：为了描述卡格列净对肠道菌群和代谢物的影响，糖尿病小鼠随机接受卡格列净或等浓度羧甲基纤维素钠灌胃，为期 8 周。收集粪便进行 16 S rRNA 基因和 LC-MS/MS 分析，并通过《京都基因与基因组百科全书》（KEGG）丰富代谢途径。根据 KEGG 富集的代谢途径收集肝脏、肌肉、肠道和脂肪进行 qRT-PCR：结果表明，卡格列净可显著提高 GLP-1 水平，并影响肠道微生物群和代谢物的组成。主要增加了 Muribaculum、Ruminococcaceae_UCG_014、Lachnospiraceae-UCG-001，减少了熊去氧胆酸（UDCA）和次去氧胆酸（HDCA），增加了粪便中的脂肪酸代谢产物：总之，我们分析了卡格列净干预后糖尿病小鼠肠道微生物组成和代谢物的变化，发现卡格列净影响了肠道脂肪酸和胆汁酸（BA）的代谢。这项研究将为后续的SGLT2i和肠道相关研究提供参考。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.