Gastric cancer: Beyond Helicobacter pylori infection

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Gastric cancer: Beyond Helicobacter pylori infection

Sexta, 28.09.2018

Gastric cancer is one of the most incident and deadly in the world. Helicobacter pylori infection plays a key role in the early stages of the process leading to the development of cancer. In this study, the authors show that there is a shift in the profile of the gastric microbiome from patients with chronic gastritis to patients with gastric cancer. The gastric microbiome of cancer patients is dysbiotic, presenting reduced microbial diversity, decreased abundance of H. pylori, and increased abundance of other species of bacteria. The authors also show that the gastric microbiome of these patients has increased genotoxic potential. The discovery of the involvement of bacteria other than H. pylori in gastric cancer development may have great impact on the clinical follow-up of patients with precancerous lesions and contribute to the prevention of stomach cancer.

This work is supported by a project funded by the Worldwide Cancer Research (https://www.worldwidecancerresearch.org/project/what-role-do-bacteria-in-our-stomach-play-in-the-development-of-cancer/).

 

Authors and Affiliations:

Rui M Ferreira1,2, Joana Pereira-Marques1,2,3, Ines Pinto-Ribeiro1,2,4, Jose L Costa1,2,4, Fatima Carneiro1,2,4,5, Jose C Machado1,2,4, Ceu Figueiredo1,2,4

1i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto; 

2Ipatimup – Institute of Molecular Pathology and Immunology of the University of Porto;

3Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto;

4Faculty of Medicine, University of Porto;

5Department of Pathology, Centro Hospitalar São João; Porto, Portugal.

 

Abstract:

Objective: Gastric carcinoma development is triggered by Helicobacter pylori. Chronic H. pylori infection leads to reduced acid secretion, which may allow the growth of a different gastric bacterial community. This change in the microbiome may increase aggression to the gastric mucosa and contribute to malignancy. Our aim was to evaluate the composition of the gastric microbiota in chronic gastritis and in gastric carcinoma.

Design: The gastric microbiota was retrospectively investigated in 54 patients with gastric carcinoma and 81 patients with chronic gastritis by 16S rRNA gene profiling, using next-generation sequencing. Differences in microbial composition of the two patient groups were assessed using linear discriminant analysis effect size. Associations between the most relevant taxa and clinical diagnosis were validated by real-time quantitative PCR. Predictive functional profiling of microbial communities was obtained with PICRUSt.

Results: The gastric carcinoma microbiota was characterised by reduced microbial diversity, by decreased abundance of Helicobacter and by the enrichment of other bacterial genera, mostly represented by intestinal commensals. The combination of these taxa into a microbial dysbiosis index revealed that dysbiosis has excellent capacity to discriminate between gastritis and gastric carcinoma. Analysis of the functional features of the microbiota was compatible with the presence of a nitrosating microbial community in carcinoma. The major observations were confirmed in validation cohorts from different geographic origins.

Conclusions: Detailed analysis of the gastric microbiota revealed for the first time that patients with gastric carcinoma exhibit a dysbiotic microbial community with genotoxic potential, which is distinct from that of patients with chronic gastritis.

 

Journal: Gut, Volume 67, issue 2, 2018

 

Link: https://gut.bmj.com/content/67/2/226