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Integrated multi-omics analyses reveal effects of empagliflozin on intestinal homeostasis in high-fat-diet mice.

ABSTRACT: Obesity has become a global epidemic, associated with several chronic complications. The intestinal microbiome is a critical regulator of metabolic homeostasis and obesity. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has putative anti-obesity effects. In this study, we used multi-omics analysis to determine whether empagliflozin regulates metabolism in an obese host through the intestinal microbiota. Compared with obese mice, the empagliflozin-treated mice had a higher species diversity of gut microbiota, characterized by a reduction in the Firmicutes/Bacteroides ratio. Metabolomic analysis unambiguously identified 1,065 small molecules with empagliflozin affecting metabolites mainly enriched in amino acid metabolism, such as tryptophan metabolism. RNA sequencing results showed that immunoglobulin A and peroxisome proliferator-activated receptor signaling pathways in the intestinal immune network were activated after empagliflozin treatment. This integrative analysis highlighted that empagliflozin maintains intestinal homeostasis by modulating gut microbiota diversity and tryptophan metabolism. This will inform the development of therapies for obesity based on host-microbe interactions.

SUBMITTER: Shi J

PROVIDER: S-EPMC9830204 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Integrated multi-omics analyses reveal effects of empagliflozin on intestinal homeostasis in high-fat-diet mice.

Shi Junfeng J Qiu Hongyan H Xu Qian Q Ma Yuting Y Ye Tongtong T Kuang Zengguang Z Qu Na N Kan Chengxia C Hou Ningning N Han Fang F Sun Xiaodong X

iScience 20221217 1

Obesity has become a global epidemic, associated with several chronic complications. The intestinal microbiome is a critical regulator of metabolic homeostasis and obesity. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has putative anti-obesity effects. In this study, we used multi-omics analysis to determine whether empagliflozin regulates metabolism in an obese host through the intestinal microbiota. Compared with obese mice, the empagliflozin-treated mice had a higher spe ...[more]

PMID: 36636340

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Integrated multi-omics analyses reveal effects of empagliflozin on intestinal homeostasis in high-fat-diet mice.

Publications

Integrated multi-omics analyses reveal effects of empagliflozin on intestinal homeostasis in high-fat-diet mice.

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