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Helicobacter pyloripromotes colorectal carcinogenesis by deregulating intestinal immunity and inducing a mucus-degrading microbiota signature
- Source :
- Gut; 2023, Vol. 72 Issue: 7 p1258-1270, 13p
- Publication Year :
- 2023
-
Abstract
- ObjectiveHelicobacter pyloriinfection is the most prevalent bacterial infection worldwide. Besides being the most important risk factor for gastric cancer development, epidemiological data show that infected individuals harbour a nearly twofold increased risk to develop colorectal cancer (CRC). However, a direct causal and functional connection between H. pyloriinfection and colon cancer is lacking.DesignWe infected two Apc-mutant mouse models and C57BL/6 mice with H. pyloriand conducted a comprehensive analysis of H. pylori-induced changes in intestinal immune responses and epithelial signatures via flow cytometry, chip cytometry, immunohistochemistry and single cell RNA sequencing. Microbial signatures were characterised and evaluated in germ-free mice and via stool transfer experiments.ResultsH. pyloriinfection accelerated tumour development in Apc-mutant mice. We identified a unique H. pylori-driven immune alteration signature characterised by a reduction in regulatory T cells and pro-inflammatory T cells. Furthermore, in the intestinal and colonic epithelium, H. pyloriinduced pro-carcinogenic STAT3 signalling and a loss of goblet cells, changes that have been shown to contribute—in combination with pro-inflammatory and mucus degrading microbial signatures—to tumour development. Similar immune and epithelial alterations were found in human colon biopsies from H. pylori-infected patients. Housing of Apc-mutant mice under germ-free conditions ameliorated, and early antibiotic eradication of H. pyloriinfection normalised the tumour incidence to the level of uninfected controls.ConclusionsOur studies provide evidence that H. pyloriinfection is a strong causal promoter of colorectal carcinogenesis. Therefore, implementation of H. pyloristatus into preventive measures of CRC should be considered.
Details
- Language :
- English
- ISSN :
- 00175749 and 14683288
- Volume :
- 72
- Issue :
- 7
- Database :
- Supplemental Index
- Journal :
- Gut
- Publication Type :
- Periodical
- Accession number :
- ejs63229439
- Full Text :
- https://doi.org/10.1136/gutjnl-2022-328075