Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota
Open accessAbstract
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.
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Hypochlorhydria promotes a reduction in microbial diversity and the growth of microbes that have genotoxic potential, with an increase in the nitrate/nitrite reductase bacterial functions involved in cancer development.
“It is important to keep in mind that hypochlorhydria promotes a reduction in microbial diversity and the growth of microbes that have genotoxic potential, with an increase in the nitrate/nitrite reductase bacterial functions involved in cancer development[60].”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [60]
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Cites
QIIME allows analysis of high-throughput community sequencing data
Caporaso, J. G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F. D., Costello, E. K., Fierer, N., Peña, A. G., Goodrich, J. K., Gordon, J. I., et al. (2010) · Nature Methods · doi:10.1038/nmeth.f.303 · Cited by 34,887 · see citing works
Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012
Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Parkin, D. M., Forman, D., & Bray, F. (2015) · International Journal of Cancer · doi:10.1002/ijc.29210 · Cited by 28,766 · see citing works
Search and clustering orders of magnitude faster than BLAST
Edgar, R. C. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq461 · Cited by 20,617 · see citing works
UPARSE: highly accurate OTU sequences from microbial amplicon reads
Edgar, R. C. (2013) · Nature Methods · doi:10.1038/nmeth.2604 · Cited by 16,587 · see citing works
Metagenomic biomarker discovery and explanation
Segata, N., Izard, J., Waldron, L., Gevers, D., Miropolsky, L., Garrett, W. S., & Huttenhower, C. (2011) · Genome Biology · doi:10.1186/gb-2011-12-6-r60 · Cited by 16,192 · see citing works
A new method for non-parametric multivariate analysis of variance
Anderson, M. J. (2001) · Austral Ecology · doi:10.1111/j.1442-9993.2001.01070.pp.x · Cited by 13,828 · see citing works
Greengenes, a Chimera-Checked 16S rRNA Gene Database and Workbench Compatible with ARB
DeSantis, T. Z., Hugenholtz, P., Larsen, N., Rojas, M., Brodie, E. L., Keller, K., Huber, T., Dalevi, D., Hu, P., & Andersen, G. L. (2006) · Applied and Environmental Microbiology · doi:10.1128/aem.03006-05 · Cited by 10,891 · see citing works
Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences
Langille, M. G. I., Zaneveld, J., Caporaso, J. G., McDonald, D., Knights, D., Reyes, J. A., Clemente, J. C., Burkepile, D. E., Vega Thurber, R. L., Knight, R., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2676 · Cited by 9,116 · see citing works
STAMP: statistical analysis of taxonomic and functional profiles
Parks, D. H., Tyson, G. W., Hugenholtz, P., & Beiko, R. G. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu494 · Cited by 4,200 · see citing works
The Treatment-Naive Microbiome in New-Onset Crohn’s Disease
Gevers, D., Kugathasan, S., Denson, L. A., Vázquez-Baeza, Y., Van Treuren, W., Ren, B., Schwager, E., Knights, D., Song, S. J., Yassour, M., et al. (2014) · Cell Host & Microbe · doi:10.1016/j.chom.2014.02.005 · Cited by 3,220 · see citing works
Correa, P. (1992) · PubMed · Cited by 3,149 · see citing works
Statistical Methods for Detecting Differentially Abundant Features in Clinical Metagenomic Samples
White, J. R., Nagarajan, N., & Pop, M. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000352 · Cited by 1,581 · see citing works
Helicobacter pylori Eradication to Prevent Gastric Cancer in a High-Risk Region of China
Wong, B. C., Lam, S. K., Wong, W. M., Chen, J. S., Zheng, T., Feng, R. E., Lai, K. C., Hu, W. H. C., Yuen, S. T., Leung, S. Y., et al. (2004) · JAMA · doi:10.1001/jama.291.2.187 · Cited by 1,436 · see citing works
Clostridium difficile--more difficult than ever.
Kelly, C. P., & Lamont, J. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0707500 · Cited by 1,386 · see citing works
Fukase, K., Kato, M., Kikuchi, S., Inoue, K., Uemura, N., Okamoto, S., Terao, S., Amagai, K., Hayashi, S., & Asaka, M. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61159-9 · Cited by 1,242 · see citing works
The first 1000 cultured species of the human gastrointestinal microbiota
Rajilić-Stojanović, M., & de Vos, W. M. (2014) · FEMS Microbiology Reviews · doi:10.1111/1574-6976.12075 · Cited by 1,182 · see citing works
Molecular analysis of the bacterial microbiota in the human stomach
Bik, E. M., Eckburg, P. B., Gill, S. R., Nelson, K. E., Purdom, E. A., François, F., Perez-Perez, G., Blaser, M. J., & Relman, D. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506655103 · Cited by 1,160 · see citing works
Comparative Analysis of Human Gut Microbiota by Barcoded Pyrosequencing
Andersson, A. F., Lindberg, M., Jakobsson, H. E., Bäckhed, F., Nyrén, P., & Engstrand, L. G. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002836 · Cited by 1,037 · see citing works
Rinttilä, T., Kassinen, A., Malinen, E., Krogius-Kurikka, L., & Palva, A. (2004) · Journal of Applied Microbiology · doi:10.1111/j.1365-2672.2004.02409.x · Cited by 1,018 · see citing works
Human Gut Microbiome and Risk for Colorectal Cancer
Ahn, J., Sinha, R., Pei, Z., Dominianni, C., Wu, J., Shi, J., Goedert, J. J., Hayes, R. B., & Yang, L. (2013) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djt300 · Cited by 947 · see citing works
Plottel, C. S., & Blaser, M. J. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.10.003 · Cited by 743 · see citing works
Mucosal microbiome dysbiosis in gastric carcinogenesis
Coker, O. O., Dai, Z., Nie, Y., Zhao, G., Cao, L., Nakatsu, G., Wu, W. K., Wong, S. H., Chen, Z., Sung, J. J. Y., et al. (2018) · Gut · doi:10.1136/gutjnl-2017-314281 · Cited by 695 · see citing works
Helicobacter pylori infection and chronic gastric acid hyposecretion
El-Omar, E. M., Oien, K. A., El-Nujumi, A., Gillen, D., Wirz, A. A., Dahill, S., Williams, C., Ardill, J., & MCCOLL, K. E. L. (1997) · Gastroenterology · doi:10.1016/s0016-5085(97)70075-1 · Cited by 642 · see citing works
Figueiredo, C. (2002) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/94.22.1680 · Cited by 629 · see citing works
Self-citationLepage, P., Häsler, R., Spehlmann, M. E., Rehman, A., Žvirblienė, A., Begun, A., Ott, S. J., Kupčinskas, L., Dore, J. M., Raedler, A., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.04.011 · Cited by 592 · see citing works
Machado, J. C., Figueiredo, C., Canedo, P., et al. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)00899-0 · Cited by 485 · see citing works
Self-citationMa, J.-L., Zhang, L., Brown, L. M., Li, W., Shen, L., Pan, K., Liu, W., Hu, Y., Han, Z.-X., Crystal-Mansour, S., et al. (2012) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djs003 · Cited by 460 · see citing works
Walters, W. A., Caporaso, J. G., Lauber, C. L., Berg-Lyons, D., Fierer, N., & Knight, R. D. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr087 · Cited by 389 · see citing works
Lofgren, J. L. S., Whary, M. T., Ge, Z., Muthupalani, S., Taylor, N. S., Mobley, M. W., Potter, A. F., Varró, A., Eibach, D., Suerbaum, S., et al. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.09.048 · Cited by 380 · see citing works
Avilés‐Jiménez, F., Vázquez‐Jiménez, F. E., Guzman, R. M., Mantilla, A., & Torres, J. (2014) · Scientific Reports · doi:10.1038/srep04202 · Cited by 340 · see citing works
Thorens, J.-J., Froehlich, F., Schwizer, W., Saraga, E. P., Billé, J., Gyr, K. E., Duroux, P., Nicolet, M., Pignatelli, B., Blum, A. L., et al. (1996) · Gut · doi:10.1136/gut.39.1.54 · Cited by 339 · see citing works
Molecular characterization of the stomach microbiota in patients with gastric cancer and in controls
Dicksved, J., Lindberg, M., Rosenquist, M., Enroth, H., Jansson, J. K., & Engstrand, L. G. (2009) · Journal of Medical Microbiology · doi:10.1099/jmm.0.007302-0 · Cited by 307 · see citing works
Structure of the human gastric bacterial community in relation to Helicobacter pylori status
Maldonado‐Contreras, A., Goldfarb, K. C., Godoy‐Vitorino, F., Karaöz, U., Contreras, M., Blaser, M. J., Brodie, E., & Domínguez-Bello, M. G. (2010) · The ISME Journal · doi:10.1038/ismej.2010.149 · Cited by 301 · see citing works
Lertpiriyapong, K., Whary, M. T., Muthupalani, S., Lofgren, J. L. S., Gamazon, E. R., Feng, Y., Ge, Z., Wang, T. C., & Fox, J. G. (2013) · Gut · doi:10.1136/gutjnl-2013-305178 · Cited by 289 · see citing works
Li, X., Wong, G. L., To, K., Wong, V. W., Lai, L. H., Chow, D. K., Lau, J. Y. W., Sung, J. J. �., & Ding, C. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007985 · Cited by 245 · see citing works
Microbiological Survey of the Human Gastric Ecosystem Using Culturing and Pyrosequencing Methods
Delgado, S., Cabrera‐Rubio, R., Mira, Á., Suárez, A., & Mayo, B. (2013) · Microbial Ecology · doi:10.1007/s00248-013-0192-5 · Cited by 228 · see citing works
Schulz, C., Schütte, K., Koch, N., Vilchez‐Vargas, R., Wos‐Oxley, M. L., Oxley, A. P. A., Vital, M., Malfertheiner, P., & Pieper, D. H. (2016) · Gut · doi:10.1136/gutjnl-2016-312904 · Cited by 221 · see citing works
Typing of Helicobacter pylori vacA Gene and Detection of cagA Gene by PCR and Reverse Hybridization
Doorn, L. J. V., Figueiredo, C., Rossau, R., et al. (1998) · Journal of Clinical Microbiology · doi:10.1128/jcm.36.5.1271-1276.1998 · Cited by 204 · see citing works
Self-citationBacterial Infection Promotes Colon Tumorigenesis in Apc Min/+ Mice
Newman, J. V., Kosaka, T., Sheppard, B. J., Fox, J. G., & Schauer, D. B. (2001) · The Journal of Infectious Diseases · doi:10.1086/321998 · Cited by 155 · see citing works
Yang, I., Woltemate, S., Piazuelo, M. B., Bravo, L. E., Yépez, M. C., Romero–Gallo, J., Delgado, A. G., Wilson, K. T., Peek, R. M., Correa, P., et al. (2016) · Scientific Reports · doi:10.1038/srep18594 · Cited by 155 · see citing works
Molecular Characterization of the Human Stomach Microbiota in Gastric Cancer Patients
Yu, G., Torres, J., Hu, N., Guzman, R. M., Herrera‐Goepfert, R., Humphrys, M. S., Wang, L., Wang, C., Ding, T., Ravel, J., et al. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00302 · Cited by 152 · see citing works
Mowat, C., Williams, C., Gillen, D., Hossack, M., Gilmour, D., Carswell, A., Wirz, A. A., Preston, T., & McColl, K. E. L. (2000) · Gastroenterology · doi:10.1053/gast.2000.9367 · Cited by 145 · see citing works
Horz, H., Vianna, M. E., Gomes, B. P. F. D. A., & Conrads, G. (2005) · Journal of Clinical Microbiology · doi:10.1128/jcm.43.10.5332-5337.2005 · Cited by 132 · see citing works
Leach, S. A., Thompson, M., & Hill, M. (1987) · Carcinogenesis · doi:10.1093/carcin/8.12.1907 · Cited by 97 · see citing works
Bacterial overgrowth as a consequence of reduced gastric acidity
Stockbruegger, R. W. (1985) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365528509093749 · Cited by 97 · see citing works
Barthold, S. W., & Jonas, A. M. (1977) · PubMed · Cited by 83 · see citing works
Nitrate- and nitrite-reducing bacteria in the achlorhydric stomach
Forsythe, S. J., Dolby, J. M., WEBSTER, A. D. B., & Cole, J. A. (1988) · Journal of Medical Microbiology · doi:10.1099/00222615-25-4-253 · Cited by 55 · see citing works
Microbial colonization of the oropharynx, esophagus and stomach in patients with gastric diseases
Sjöstedt, S., Heimdahl, A., Kager, L., et al. (1985) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/bf02148660 · Cited by 45 · see citing works
Jiao, Y. S., Yan, H., Ji, Z. J., et al. (2014) · INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY · doi:10.1099/ijs.0.067017-0 · Cited by 44 · see citing works
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- Authors
- Ferreira, R. M., Pereira-Marques, J., Pinto-Ribeiro, I., Costa, J. L., Carneiro, F., Machado, J. C., & Figueiredo, C.
- Affiliations
- Universidade do Porto (PT)
- i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2017-11-04
- Volume
- 67
- Issue
- 2
- Pages
- 226-236
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC5868293
- OpenAlex
- W2765111042
- Cited by
- 697
- References
- 49
- Citations by year
- 2026: 68 · 2025: 85 · 2024: 86 · 2023: 92 · 2022: 105 · 2021: 97 · 2020: 80 · 2019: 55 · 2018: 28
- FWCI
- 45.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Gut (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by)
- Funders
- Worldwide Cancer Research
- Topics
- Health Sciences › Medicine › Surgery › Helicobacter pylori-related gastroenterology studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gastric Cancer Management and Outcomes
- Keywords
- gastric microbiota, dysbiosis, gastric cancer, chronic gastritis, genotoxicity, intestinal commensals, acid secretion, 16S rRNA gene profiling
- MeSH terms
- Gastrointestinal Microbiome, Adult, Aged, Bacteria, Carcinoma, Chronic Disease, Female, Gastric Mucosa, Gastritis, Humans, Male, Middle Aged, Retrospective Studies, RNA, Ribosomal, 16S, Stomach, Stomach Neoplasms, Nitrosation, Helicobacter pylori, Helicobacter Infections, Dysbiosis
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