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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Funding
This study was supported by the Foundation of Sichuan Science and Technology (No. 2020YJ0461; granted to MZ) and the Foundation of Sichuan Provincial People’s Hospital (No. 2022QN14; granted to LZ).
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Conception and design: LZ, MZ, JM;Methodology: JM, TW, HW, GY, CH, TZ; Acquisition of data: JM, TW, HW, GY, CH, TZ ; Analysis and interpretation of data: LZ, HT, JM, TW; Writing of the manuscript: LZ; Writing and approval of the final draft: LZ, JM, HT, MZ ; Study supervision: HT, MZ. All authors read and approved the final version of this manuscript.
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Zeng, L., Ma, J., Wei, T. et al. The effect of canagliflozin on gut microbiota and metabolites in type 2 diabetic mice. Genes Genom 46, 541–555 (2024). https://doi.org/10.1007/s13258-024-01491-0
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DOI: https://doi.org/10.1007/s13258-024-01491-0