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Original article
Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota
  1. Rui M Ferreira1,2,
  2. Joana Pereira-Marques1,2,3,
  3. Ines Pinto-Ribeiro1,2,4,
  4. Jose L Costa1,2,4,
  5. Fatima Carneiro1,2,4,5,
  6. Jose C Machado1,2,4,
  7. Ceu Figueiredo1,2,4
  1. 1 i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
  2. 2 Ipatimup – Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
  3. 3 Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal
  4. 4 Faculty of Medicine, University of Porto, Porto, Portugal
  5. 5 Department of Pathology, Centro Hospitalar São João, Porto, Portugal
  1. Correspondence to Professor Ceu Figueiredo, Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal; cfigueiredo{at}ipatimup.pt

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.

  • gastric carcinoma
  • gastritis
  • Helicobacter pylori
  • bacterial infection

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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Footnotes

  • Contributors Study concept and design: CF, JCM. Data acquisition, analysis and interpretation: CF, JCM, RMF, JPM, IPR, JLC, FC. Drafting of the manuscript or revising it critically for important intellectual content: CF, JCM, RMF, JPM, IPR, JLC, FC. Obtained funding: CF, JCM.

  • Funding This research was supported by a Worldwide Cancer Research grant to CF and JCM (Reference 16-1352). RMF, JPM and IPR have fellowships from Fundação para a Ciência e a Tecnologia (FCT; SFRH/BPD/84084/2012, PD/BD/114014/2015 and SFRH/BD/110803/2015, respectively) through Programa Operacional Capital Humano (POCH) and the European Union. JPM’s fellowship is in the framework of FCT’s PhD Programme BiotechHealth (Ref PD/0016/2012). i3S-Instituto de Investigação e Inovação em Saúde is funded by Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through Fundação para a Ciência e a Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Inovação (POCI-01-0145-FEDER-007274).

  • Competing interests None declared.

  • Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.

  • Ethics approval Ethics Committee Centro Hospitalar São João.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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