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Ralser, A.* ; Dietl, A.* ; Jarosch, S.* ; Engelsberger, V.* ; Wanisch, A.* ; Janssen, K.P.* ; Middelhoff, M.* ; Vieth, M.* ; Quante, M.* ; Haller, D.* ; Busch, D.* ; Deng, L. ; Mejías-Luque, R.* ; Gerhard, M.*

Helicobacter pylori promotes colorectal carcinogenesis by deregulating intestinal immunity and inducing a mucus-degrading microbiota signature.

Gut 72, 1258-1270 (2023)
Postprint DOI PMC
Open Access Green
OBJECTIVE: Helicobacter pylori infection 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. pylori infection and colon cancer is lacking. DESIGN: We infected two Apc-mutant mouse models and C57BL/6 mice with H. pylori and 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. RESULTS: H. pylori infection 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. pylori induced 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. pylori infection normalised the tumour incidence to the level of uninfected controls. CONCLUSIONS: Our studies provide evidence that H. pylori infection is a strong causal promoter of colorectal carcinogenesis. Therefore, implementation of H. pylori status into preventive measures of CRC should be considered.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Helicobacter Pylori ; Colonic Microflora ; Colorectal Cancer ; Immune Response ; Signaling; Foxp3(+)il-17(+) T-cells; Tumor Progression; Gut Microbiota; Stat3; Activation; Colitis; Cancer; Th17; Differentiation; Responses
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 0017-5749
e-ISSN 1468-3288
Zeitschrift Gut (eGut)
Quellenangaben Band: 72, Heft: 7, Seiten: 1258-1270 Artikelnummer: , Supplement: ,
Verlag BMJ Publishing Group
Verlagsort British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-554300-001
Förderungen Deutsche Forschungsgemeinschaft (DFG (German Research Foundation))
DOI 10.1136/gutjnl-2022-328075
WOS ID 000969466100001
Scopus ID 85160260742
PubMed ID 37015754
Erfassungsdatum 2023-10-06
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