Exploring the mechanism of intestinal bacterial translocation after severe acute pancreatitis: the role of Toll-like receptor 5
Severe acute pancreatitis (SAP)-induced intestinal bacterial translocation and enterogenic infection are among the leading causes of mortality in patients. However, the mechanisms by which SAP disrupted the intestinal barrier and led to bacterial translocation remained unclear. Therefore, we employe...
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| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2025.2489768 |
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| author | Cheng Zhang Shiyin Chen Zhien Wang Jian Zhang Wenqiao Yu Yanshuai Wang Weiwei Si Yuwei Zhang Yun Zhang Tingbo Liang |
| author_facet | Cheng Zhang Shiyin Chen Zhien Wang Jian Zhang Wenqiao Yu Yanshuai Wang Weiwei Si Yuwei Zhang Yun Zhang Tingbo Liang |
| author_sort | Cheng Zhang |
| collection | DOAJ |
| description | Severe acute pancreatitis (SAP)-induced intestinal bacterial translocation and enterogenic infection are among the leading causes of mortality in patients. However, the mechanisms by which SAP disrupted the intestinal barrier and led to bacterial translocation remained unclear. Therefore, we employed multi-omics analysis including microbiome, metabolome, epigenome, transcriptome, and mass cytometry (CyTOF) to identify potential targets, followed by functional validation using transgenic mice. The integrated multi-omics analysis primarily indicated overgrowth of intestinal flagellated bacteria, upregulation of intestinal Toll-like receptor 5 (TLR5) and acute inflammatory response, and increased infiltration of intestinal high-expressing TLR5 lamina propria dendritic cells (TLR5hi LPDC) after SAP. Subsequently, intestinal flagellin-TLR5 signaling was activated after SAP. Intestinal barrier disruption, bacterial translocation, and helper T cells (Th) differentiation imbalance caused by SAP were alleviated in TLR5 knocked out (Tlr5−/−) or conditionally knocked out on LPDC (Tlr5ΔDC) mice. However, TLR5 conditional knockout on intestinal epithelial cells (Tlr5ΔIEC) failed to improve SAP-induced bacterial translocation. Moreover, depletion of LPDC and regulatory T cells (Treg) ameliorated bacterial translocation after SAP. Our findings identify TLR5 on LPDC as a potential novel target for preventing or treating intestinal bacterial translocation caused by SAP. |
| format | Article |
| id | doaj-art-2171a2737e9044df800b2d0384fe5e5f |
| institution | OA Journals |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-2171a2737e9044df800b2d0384fe5e5f2025-08-20T02:25:43ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2489768Exploring the mechanism of intestinal bacterial translocation after severe acute pancreatitis: the role of Toll-like receptor 5Cheng Zhang0Shiyin Chen1Zhien Wang2Jian Zhang3Wenqiao Yu4Yanshuai Wang5Weiwei Si6Yuwei Zhang7Yun Zhang8Tingbo Liang9Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, ChinaDepartment of Rehabilitation, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, ChinaDepartment of Surgical Intensive Care Unit, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, ChinaCollege of Science, Mathematics and Technology, Wenzhou-Kean University, Wenzhou, Zhejiang Province, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, ChinaSevere acute pancreatitis (SAP)-induced intestinal bacterial translocation and enterogenic infection are among the leading causes of mortality in patients. However, the mechanisms by which SAP disrupted the intestinal barrier and led to bacterial translocation remained unclear. Therefore, we employed multi-omics analysis including microbiome, metabolome, epigenome, transcriptome, and mass cytometry (CyTOF) to identify potential targets, followed by functional validation using transgenic mice. The integrated multi-omics analysis primarily indicated overgrowth of intestinal flagellated bacteria, upregulation of intestinal Toll-like receptor 5 (TLR5) and acute inflammatory response, and increased infiltration of intestinal high-expressing TLR5 lamina propria dendritic cells (TLR5hi LPDC) after SAP. Subsequently, intestinal flagellin-TLR5 signaling was activated after SAP. Intestinal barrier disruption, bacterial translocation, and helper T cells (Th) differentiation imbalance caused by SAP were alleviated in TLR5 knocked out (Tlr5−/−) or conditionally knocked out on LPDC (Tlr5ΔDC) mice. However, TLR5 conditional knockout on intestinal epithelial cells (Tlr5ΔIEC) failed to improve SAP-induced bacterial translocation. Moreover, depletion of LPDC and regulatory T cells (Treg) ameliorated bacterial translocation after SAP. Our findings identify TLR5 on LPDC as a potential novel target for preventing or treating intestinal bacterial translocation caused by SAP.https://www.tandfonline.com/doi/10.1080/19490976.2025.2489768Toll-like receptor 5bacterial translocationpancreatitisdendritic cellsregulatory T cells |
| spellingShingle | Cheng Zhang Shiyin Chen Zhien Wang Jian Zhang Wenqiao Yu Yanshuai Wang Weiwei Si Yuwei Zhang Yun Zhang Tingbo Liang Exploring the mechanism of intestinal bacterial translocation after severe acute pancreatitis: the role of Toll-like receptor 5 Gut Microbes Toll-like receptor 5 bacterial translocation pancreatitis dendritic cells regulatory T cells |
| title | Exploring the mechanism of intestinal bacterial translocation after severe acute pancreatitis: the role of Toll-like receptor 5 |
| title_full | Exploring the mechanism of intestinal bacterial translocation after severe acute pancreatitis: the role of Toll-like receptor 5 |
| title_fullStr | Exploring the mechanism of intestinal bacterial translocation after severe acute pancreatitis: the role of Toll-like receptor 5 |
| title_full_unstemmed | Exploring the mechanism of intestinal bacterial translocation after severe acute pancreatitis: the role of Toll-like receptor 5 |
| title_short | Exploring the mechanism of intestinal bacterial translocation after severe acute pancreatitis: the role of Toll-like receptor 5 |
| title_sort | exploring the mechanism of intestinal bacterial translocation after severe acute pancreatitis the role of toll like receptor 5 |
| topic | Toll-like receptor 5 bacterial translocation pancreatitis dendritic cells regulatory T cells |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2025.2489768 |
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