Cargando…

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

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 mu...

Descripción completa

Detalles Bibliográficos
Autores principales: Shi, Junfeng, Qiu, Hongyan, Xu, Qian, Ma, Yuting, Ye, Tongtong, Kuang, Zengguang, Qu, Na, Kan, Chengxia, Hou, Ningning, Han, Fang, Sun, Xiaodong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9830204/
https://www.ncbi.nlm.nih.gov/pubmed/36636340
http://dx.doi.org/10.1016/j.isci.2022.105816
_version_ 1784867622985138176
author Shi, Junfeng
Qiu, Hongyan
Xu, Qian
Ma, Yuting
Ye, Tongtong
Kuang, Zengguang
Qu, Na
Kan, Chengxia
Hou, Ningning
Han, Fang
Sun, Xiaodong
author_facet Shi, Junfeng
Qiu, Hongyan
Xu, Qian
Ma, Yuting
Ye, Tongtong
Kuang, Zengguang
Qu, Na
Kan, Chengxia
Hou, Ningning
Han, Fang
Sun, Xiaodong
author_sort Shi, Junfeng
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9830204
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-98302042023-01-11 Integrated multi-omics analyses reveal effects of empagliflozin on intestinal homeostasis in high-fat-diet mice Shi, Junfeng Qiu, Hongyan Xu, Qian Ma, Yuting Ye, Tongtong Kuang, Zengguang Qu, Na Kan, Chengxia Hou, Ningning Han, Fang Sun, Xiaodong iScience Article 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. Elsevier 2022-12-17 /pmc/articles/PMC9830204/ /pubmed/36636340 http://dx.doi.org/10.1016/j.isci.2022.105816 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Shi, Junfeng
Qiu, Hongyan
Xu, Qian
Ma, Yuting
Ye, Tongtong
Kuang, Zengguang
Qu, Na
Kan, Chengxia
Hou, Ningning
Han, Fang
Sun, Xiaodong
Integrated multi-omics analyses reveal effects of empagliflozin on intestinal homeostasis in high-fat-diet mice
title Integrated multi-omics analyses reveal effects of empagliflozin on intestinal homeostasis in high-fat-diet mice
title_full Integrated multi-omics analyses reveal effects of empagliflozin on intestinal homeostasis in high-fat-diet mice
title_fullStr Integrated multi-omics analyses reveal effects of empagliflozin on intestinal homeostasis in high-fat-diet mice
title_full_unstemmed Integrated multi-omics analyses reveal effects of empagliflozin on intestinal homeostasis in high-fat-diet mice
title_short Integrated multi-omics analyses reveal effects of empagliflozin on intestinal homeostasis in high-fat-diet mice
title_sort integrated multi-omics analyses reveal effects of empagliflozin on intestinal homeostasis in high-fat-diet mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9830204/
https://www.ncbi.nlm.nih.gov/pubmed/36636340
http://dx.doi.org/10.1016/j.isci.2022.105816
work_keys_str_mv AT shijunfeng integratedmultiomicsanalysesrevealeffectsofempagliflozinonintestinalhomeostasisinhighfatdietmice
AT qiuhongyan integratedmultiomicsanalysesrevealeffectsofempagliflozinonintestinalhomeostasisinhighfatdietmice
AT xuqian integratedmultiomicsanalysesrevealeffectsofempagliflozinonintestinalhomeostasisinhighfatdietmice
AT mayuting integratedmultiomicsanalysesrevealeffectsofempagliflozinonintestinalhomeostasisinhighfatdietmice
AT yetongtong integratedmultiomicsanalysesrevealeffectsofempagliflozinonintestinalhomeostasisinhighfatdietmice
AT kuangzengguang integratedmultiomicsanalysesrevealeffectsofempagliflozinonintestinalhomeostasisinhighfatdietmice
AT quna integratedmultiomicsanalysesrevealeffectsofempagliflozinonintestinalhomeostasisinhighfatdietmice
AT kanchengxia integratedmultiomicsanalysesrevealeffectsofempagliflozinonintestinalhomeostasisinhighfatdietmice
AT houningning integratedmultiomicsanalysesrevealeffectsofempagliflozinonintestinalhomeostasisinhighfatdietmice
AT hanfang integratedmultiomicsanalysesrevealeffectsofempagliflozinonintestinalhomeostasisinhighfatdietmice
AT sunxiaodong integratedmultiomicsanalysesrevealeffectsofempagliflozinonintestinalhomeostasisinhighfatdietmice