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.

中文翻译：

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卡格列净对2型糖尿病小鼠肠道菌群和代谢物的影响

背景

钠葡萄糖协同转运蛋白2抑制剂（SGLT2i）是一种新型降血糖药物，可导致葡萄糖从尿液中大量流失，具有减轻体重、改善心血管和肾脏疾病预后等多种益处。尽管它们是口服降糖药，但它们对肠道微生物组和功能的影响尚不清楚。

客观的

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，并通过京都基因和基因组百科全书 (KEGG) 丰富代谢途径。根据KEGG富集代谢途径收集肝脏、肌肉、肠道、脂肪进行qRT-PCR。

结果

我们的结果表明，卡格列净显着增加 GLP-1 水平，并影响肠道微生物群和代谢物的组成。主要增加Muribaculum、Ruminococcaceae_UCG_014、Lachnospiraceae-UCG-001，减少熊去氧胆酸（UDCA）和猪去氧胆酸（HDCA），以及增加粪便中的脂肪酸代谢物。

结论

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，发现卡格列净影响肠道脂肪酸和胆汁酸（BA）代谢。本研究将为后续SGLT2i及肠道相关研究提供参考。