The Type III Secretion System (T3SS) of Escherichia Coli Promotes Atherosclerosis in Type 2 Diabetes Mellitus
Abstract Large‐scale studies indicate a strong relationship between the gut microbiome, type 2 diabetes mellitus (T2DM), and atherosclerotic cardiovascular disease (ASCVD). Here, a higher abundance of the type III secretion system (T3SS) virulence factors of Enterobacteriaceae/Escherichia‐Shigella i...
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Wiley
2025-04-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202413296 |
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| author | Yao‐Yuan Zhang Song‐Tao Chen Gang Chen Le Zhou Guo‐Liang Zhou Xin‐Yuan Yu Long Yuan Wei‐Qian Deng Zhen‐Bo Wang Jing Li Yi‐Fu Tu Da‐Wei Zhang Yuan li Abdul Sammad Xiao Zhu Kai Yin |
| author_facet | Yao‐Yuan Zhang Song‐Tao Chen Gang Chen Le Zhou Guo‐Liang Zhou Xin‐Yuan Yu Long Yuan Wei‐Qian Deng Zhen‐Bo Wang Jing Li Yi‐Fu Tu Da‐Wei Zhang Yuan li Abdul Sammad Xiao Zhu Kai Yin |
| author_sort | Yao‐Yuan Zhang |
| collection | DOAJ |
| description | Abstract Large‐scale studies indicate a strong relationship between the gut microbiome, type 2 diabetes mellitus (T2DM), and atherosclerotic cardiovascular disease (ASCVD). Here, a higher abundance of the type III secretion system (T3SS) virulence factors of Enterobacteriaceae/Escherichia‐Shigella in patients with T2DM‐related‐ASCVD, which correlates with their atherosclerotic stenosis is reported. Overexpression of T3SS via Citrobacter rodentium (CR) infection in Apoe‐/‐ T2DM mice exacerbated atherosclerotic lesion formation and increased gut permeability. Non‐targeted metabolomic and proteomic analysis of mouse serum showed that T3SS caused abnormal glycerophospholipid metabolism in mice. Proteomics, RNA sequencing, and functional analyses showed that T3SS induced ferroptosis in intestinal epithelial cells, partly due to increased expression of ferritin heavy chains (FTH1). This findings first demonstrated that T3SS increases ferroptosis in intestinal epithelial cells, via disrupting the intestinal barrier and upregulation of phosphatidylcholine, thereby exacerbating T2DM‐related ASCVD. |
| format | Article |
| id | doaj-art-cc9ecd8c1be04ce7b26d7f41f23d29a2 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-cc9ecd8c1be04ce7b26d7f41f23d29a22025-08-20T02:26:45ZengWileyAdvanced Science2198-38442025-04-011215n/an/a10.1002/advs.202413296The Type III Secretion System (T3SS) of Escherichia Coli Promotes Atherosclerosis in Type 2 Diabetes MellitusYao‐Yuan Zhang0Song‐Tao Chen1Gang Chen2Le Zhou3Guo‐Liang Zhou4Xin‐Yuan Yu5Long Yuan6Wei‐Qian Deng7Zhen‐Bo Wang8Jing Li9Yi‐Fu Tu10Da‐Wei Zhang11Yuan li12Abdul Sammad13Xiao Zhu14Kai Yin15Department of General Practice The Fifth Affiliated Hospital of Southern Medical University Guangzhou 510515 ChinaDepartment of General Practice The Fifth Affiliated Hospital of Southern Medical University Guangzhou 510515 ChinaDepartment of General Practice The Fifth Affiliated Hospital of Southern Medical University Guangzhou 510515 ChinaDepartment of General Practice The Fifth Affiliated Hospital of Southern Medical University Guangzhou 510515 ChinaDepartment of Cardiology The Second Affiliated Hospital of Guilin Medical University Guilin 541199 ChinaDepartment of General Practice The Fifth Affiliated Hospital of Southern Medical University Guangzhou 510515 ChinaDepartment of General Practice The Fifth Affiliated Hospital of Southern Medical University Guangzhou 510515 ChinaDepartment of General Practice The Fifth Affiliated Hospital of Southern Medical University Guangzhou 510515 ChinaDepartment of General Practice The Fifth Affiliated Hospital of Southern Medical University Guangzhou 510515 ChinaDepartment of Imaging Diagnosis Zhujiang Hospital of Southern Medical University Guangzhou 510515 ChinaDepartment of General Practice The Fifth Affiliated Hospital of Southern Medical University Guangzhou 510515 ChinaGroup on the Molecular and Cell Biology of Lipids and Department of Pediatrics Faculty of Medicine and Dentistry University of Alberta Edmonton Alberta T6G 2R3 CanadaDepartment of General Practice The Fifth Affiliated Hospital of Southern Medical University Guangzhou 510515 ChinaDepartment of General Practice The Fifth Affiliated Hospital of Southern Medical University Guangzhou 510515 ChinaDepartment of General Practice The Fifth Affiliated Hospital of Southern Medical University Guangzhou 510515 ChinaDepartment of General Practice The Fifth Affiliated Hospital of Southern Medical University Guangzhou 510515 ChinaAbstract Large‐scale studies indicate a strong relationship between the gut microbiome, type 2 diabetes mellitus (T2DM), and atherosclerotic cardiovascular disease (ASCVD). Here, a higher abundance of the type III secretion system (T3SS) virulence factors of Enterobacteriaceae/Escherichia‐Shigella in patients with T2DM‐related‐ASCVD, which correlates with their atherosclerotic stenosis is reported. Overexpression of T3SS via Citrobacter rodentium (CR) infection in Apoe‐/‐ T2DM mice exacerbated atherosclerotic lesion formation and increased gut permeability. Non‐targeted metabolomic and proteomic analysis of mouse serum showed that T3SS caused abnormal glycerophospholipid metabolism in mice. Proteomics, RNA sequencing, and functional analyses showed that T3SS induced ferroptosis in intestinal epithelial cells, partly due to increased expression of ferritin heavy chains (FTH1). This findings first demonstrated that T3SS increases ferroptosis in intestinal epithelial cells, via disrupting the intestinal barrier and upregulation of phosphatidylcholine, thereby exacerbating T2DM‐related ASCVD.https://doi.org/10.1002/advs.202413296atherosclerosisferroptosisintestinal barrierphosphatidylcholineT2DMT3SS |
| spellingShingle | Yao‐Yuan Zhang Song‐Tao Chen Gang Chen Le Zhou Guo‐Liang Zhou Xin‐Yuan Yu Long Yuan Wei‐Qian Deng Zhen‐Bo Wang Jing Li Yi‐Fu Tu Da‐Wei Zhang Yuan li Abdul Sammad Xiao Zhu Kai Yin The Type III Secretion System (T3SS) of Escherichia Coli Promotes Atherosclerosis in Type 2 Diabetes Mellitus Advanced Science atherosclerosis ferroptosis intestinal barrier phosphatidylcholine T2DM T3SS |
| title | The Type III Secretion System (T3SS) of Escherichia Coli Promotes Atherosclerosis in Type 2 Diabetes Mellitus |
| title_full | The Type III Secretion System (T3SS) of Escherichia Coli Promotes Atherosclerosis in Type 2 Diabetes Mellitus |
| title_fullStr | The Type III Secretion System (T3SS) of Escherichia Coli Promotes Atherosclerosis in Type 2 Diabetes Mellitus |
| title_full_unstemmed | The Type III Secretion System (T3SS) of Escherichia Coli Promotes Atherosclerosis in Type 2 Diabetes Mellitus |
| title_short | The Type III Secretion System (T3SS) of Escherichia Coli Promotes Atherosclerosis in Type 2 Diabetes Mellitus |
| title_sort | type iii secretion system t3ss of escherichia coli promotes atherosclerosis in type 2 diabetes mellitus |
| topic | atherosclerosis ferroptosis intestinal barrier phosphatidylcholine T2DM T3SS |
| url | https://doi.org/10.1002/advs.202413296 |
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