Gastric microbiota is altered in oesophagitis and B arrett's oesophagus and further modified by proton pump inhibitors
Abstract
Summary: Gastro‐oesophageal reflux can cause inflammation, metaplasia, dysplasia and cancer of the oesophagus. Despite the increased use of proton pump inhibitors ( PPIs ) to treat reflux, the incidence of oesophageal adenocarcinoma has increased rapidly in E urope and in the U nited S tates in the last 25 years. The reasons for this increase remain unclear. In this study, we aimed to determine whether the microbiota of the gastric refluxate and oesophageal biopsies differs between patients with heartburn and normal‐appearing oesophageal mucosa versus patients with abnormal oesophageal mucosa [oesophagitis or B arrett's oesophagus ( BE )] and to elucidate the effect of PPIs on the bacterial communities using 16 S rRNA gene pyrosequencing. Significant differences in the composition of gastric fluid bacteria were found between patients with heartburn and normal oesophageal tissue versus patients with oesophagitis or BE , but in the oesophagus‐associated microbiota differences were relatively modest. Notably, increased levels of E nterobacteriaceae were observed in the gastric fluid of oesophagitis and BE patients. In addition, treatment with PPIs had dramatic effects on microbial communities both in the gastric fluids and the oesophageal tissue. In conclusion, gastric fluid microbiota is modified in patients with oesophagitis and BE compared with heartburn patients with normal biopsies. Furthermore, PPI treatment markedly alters gastric and oesophageal microbial populations. Determining whether the changes in bacterial composition caused by PPIs are beneficial or harmful will require further investigation.
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PPI treatment can alter esophageal microbiota, causing an increase in the abundance of Firmicutes and a decrease in the abundance of Bacteroidetes and Proteobacteria.
“PPI treatment can alter esophageal microbiota, causing an increase in the abundance of Firmicutes and a decrease in the abundance of Bacteroidetes and Proteobacteria[47].”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [47]
Cites
Jemal, A., Bray, F., Ferlay, J., Ward, E., & Forman, D. (2011) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20107 · Cited by 54,708 · see citing works
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
Naive Bayesian Classifier for Rapid Assignment of rRNA Sequences into the New Bacterial Taxonomy
Wang, Q., Garrity, G. M., Tiedje, J. M., & Cole, J. R. (2007) · Applied and Environmental Microbiology · doi:10.1128/aem.00062-07 · Cited by 19,770 · 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
Chimeric 16S rRNA sequence formation and detection in Sanger and 454-pyrosequenced PCR ampliconsPreprint
Haas, B. J., Gevers, D., Earl, A. M., Feldgarden, M., Ward, D. V., Giannoukos, G., Ciulla, D., Tabbaa, D., Highlander, S. K., Sodergren, E. J., et al. (2011) · Genome Research · doi:10.1101/gr.112730.110 · Cited by 3,480 · see citing works
PyNAST: a flexible tool for aligning sequences to a template alignment
Caporaso, J. G., Bittinger, K. L., Bushman, F. D., DeSantis, T. Z., Andersen, G. L., & Knight, R. D. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp636 · Cited by 3,374 · see citing works
The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice
Turnbaugh, P. J., Ridaura, V. K., Faith, J. J., Rey, F. E., Knight, R., & Gordon, J. I. (2009) · Science Translational Medicine · doi:10.1126/scitranslmed.3000322 · Cited by 3,058 · see citing works
Epidemiology of gastro-oesophageal reflux disease: a systematic review
Dent, J. (2005) · Gut · doi:10.1136/gut.2004.051821 · Cited by 1,885 · see citing works
Incidence of Adenocarcinoma among Patients with Barrett's Esophagus
Hvid‐Jensen, F., Pedersen, L. H., Drewes, A. M., Sørensen, H. T., & Funch-Jensen, P. M. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103042 · Cited by 1,370 · 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
Rajilić–Stojanović, M., Biagi, E., Heilig, H. G. H. J., Kajander, K., Kekkonen, R. A., Tims, S., & de Vos, W. M. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.07.043 · Cited by 1,041 · see citing works
Garrett, W. S., Gallini, C. A., Yatsunenko, T., Michaud, M., DuBois, A., Delaney, M. L., Punit, S., Karlsson, M., Bry, L., Glickman, J. N., et al. (2010) · Cell Host & Microbe · doi:10.1016/j.chom.2010.08.004 · Cited by 788 · see citing works
Cancers with increasing incidence trends in the United States: 1999 through 2008
Simard, E. P., Ward, E., Siegel, R. L., & Jemal, A. (2012) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20141 · Cited by 723 · see citing works
Spechler, S. J., & Goyal, R. K. (1986) · New England Journal of Medicine · doi:10.1056/nejm198608073150605 · Cited by 664 · see citing works
Bacterial biota in the human distal esophagus
Pei, Z., Bini, E. J., Yang, L., Zhou, M., Francois, F., & Blaser, M. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0306398101 · Cited by 501 · see citing works
Yang, L., Lü, X., Nossa, C. W., François, F., Peek, R. M., & Pei, Z. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.04.046 · Cited by 488 · see citing works
Bavishi, C., & DuPont, H. L. (2011) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2011.04874.x · Cited by 480 · see citing works
Absence of intestinal microbiota does not protect mice from diet-induced obesity
Fleissner, C. K., Huebel, N., Abd El-Bary, M. M., Loh, G., Klaus, S., & Blaut, M. (2010) · British Journal of Nutrition · doi:10.1017/s0007114510001303 · Cited by 436 · see citing works
Esophageal Adenocarcinoma Incidence: Are We Reaching the Peak?
Pohl, H., Sirovich, B., & Welch, H. G. (2010) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-10-0012 · Cited by 420 · see citing works
Dowd, S. E., Sun, Y., Wolcott, R. D., Domingo, A., & Carroll, J. A. (2008) · Foodborne Pathogens and Disease · doi:10.1089/fpd.2008.0107 · Cited by 417 · see citing works
Sikkema, M., de Jonge, P. J. F., Steyerberg, E. W., et al. (2009) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2009.10.010 · Cited by 355 · see citing works
The Effects of Alcohol Consumption Upon The Gastrointestinal Tract
Bujanda, L. (2000) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2000.03347.x · Cited by 351 · see citing works
Helicobacter pylori and Esophageal Cancer Risk: A Meta-analysis
Islami, F., & Kamangar, F. (2008) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-08-0109 · Cited by 321 · see citing works
Predicting ultraviolet spectrum of single stranded and double stranded deoxyribonucleic acids
Tataurov, A. V., You, Y., & Owczarzy, R. (2007) · Biophysical Chemistry · doi:10.1016/j.bpc.2007.12.004 · Cited by 282 · see citing works
Relationship Between Helicobacter pylori Infection and Esophageal Neoplasia: A Meta-analysis
Rokkas, T., Pistiolas, D., Sechopoulos, P., Robotis, I., & Margantinis, G. (2007) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2007.08.010 · Cited by 230 · see citing works
Theisen, J., Nehra, D., Citron, D. M., Johansson, J., Hagen, J. A., Crookes, P. F., DeMeester, S. R., Bremner, C. G., DeMeester, T. R., & Peters, J. H. (2000) · Journal of Gastrointestinal Surgery · doi:10.1016/s1091-255x(00)80032-3 · Cited by 216 · see citing works
Zhao, H., Ginkel, S. W. V., Tang, Y., Kang, D., Rittmann, B. E., & Krajmalnik‐Brown, R. (2011) · Environmental Science & Technology · doi:10.1021/es202569b · Cited by 153 · see citing works
The Effect of Proton Pump Inhibitors on the Human Microbiota
Vesper, B. J., Jawdi, A., Altman, K. W., Haines, G. K., Tao, L., & Radosevich, J. A. (2009) · Current Drug Metabolism · doi:10.2174/138920009787048392 · Cited by 145 · see citing works
Ronkainen, J., Talley, N. J., Storskrubb, T., et al. (2011) · The American Journal of Gastroenterology · doi:10.1038/ajg.2011.326 · Cited by 123 · see citing works
Hage, M., Siersema, P. D., Dekken, H. V., et al. (2004) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365520410003524 · Cited by 110 · see citing works
Disappearing Microbiota: Helicobacter pylori Protection against Esophageal Adenocarcinoma
Blaser, M. J. (2008) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-08-0170 · Cited by 108 · see citing works
Sun, Y., Wolcott, R. D., & Dowd, S. E. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-089-8_9 · Cited by 104 · see citing works
Sultan, N., Nazareno, J., & Gregor, J. C. (2008) · Canadian Journal of Gastroenterology · doi:10.1155/2008/821385 · Cited by 79 · see citing works
Barrett's esophagus and esophageal adenocarcinoma: pathogenesis, diagnosis, and therapy
Spechler, S. J. (2002) · Medical Clinics of North America · doi:10.1016/s0025-7125(02)00082-2 · Cited by 76 · see citing works
Epidemiology of Barrett’s esophagus and adenocarcinoma*
Cameron, A. J. (2002) · Diseases of the Esophagus · doi:10.1046/j.1442-2050.2002.00216.x · Cited by 66 · see citing works
Conventional dose of omeprazole alters gastric flora
Karmeli, Y., Stalnikowitz, R., Eliakim, R., & Rahav, G. (1995) · Digestive Diseases and Sciences · doi:10.1007/bf02208680 · Cited by 55 · see citing works
Long-term treatment with proton pump inhibitor is associated with undesired weight gain
Yoshikawa, I., Nagato, M., Yamasaki, M., et al. (2009) · World Journal of Gastroenterology · doi:10.3748/wjg.15.4794 · Cited by 30 · see citing works
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Imhann, F., Bonder, M. J., Vich Vila, A., Fu, J., Mujagic, Z., Vork, L., Tigchelaar, E. F., Jankipersadsing, S. A., Cenit, M. C., Harmsen, H. J. M., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-310376 · Cited by 1,371 · see citing works
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Jackson, M. A., Goodrich, J. K., Maxan, M.-E., Freedberg, D. E., Abrams, J. A., Poole, A. C., Sutter, J. L., Welter, D., Ley, R. E., Bell, J. T., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-310861 · Cited by 895 · see citing works
Trifan, A., Stanciu, C., Girleanu, I., Stoica, O. C., Singeap, A. M., Maxim, R., Chiriac, S. A., Ciobica, A., & Boiculese, L. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i35.6500 · Cited by 286 · see citing works
Hsieh, Y.-Y., Tung, S.-Y., Pan, H.-Y., Yen, C.-W., Xu, H.-W., Lin, Y.-J., Deng, Y.-F., Hsu, W.-T., Wu, C.-S., & Li, C. (2018) · Scientific Reports · doi:10.1038/s41598-017-18596-0 · Cited by 269 · see citing works
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Bruno, G., Zaccari, P., Rocco, G., Scalese, G., Panetta, C., Porowska, B., Pontone, S., & Severi, C. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i22.2706 · Cited by 258 · see citing works
McDonald, E. G., Milligan, J., Frenette, C., & Lee, T. C. (2015) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2015.42 · Cited by 216 · see citing works
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Tsuda, A., Suda, W., Morita, H., Takanashi, K., Takagi, A., Koga, Y., & Hattori, M. (2015) · Clinical and Translational Gastroenterology · doi:10.1038/ctg.2015.20 · Cited by 164 · see citing works
Bajaj, J. S., Cox, I. J., Betrapally, N. S., Heuman, D. M., Schubert, M. L., Ratneswaran, M., Hylemon, P. B., White, M. B., Daita, K., Noble, N. A., et al. (2014) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00268.2014 · Cited by 143 · see citing works
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Di Pilato, V., Freschi, G., Ringressi, M. N., Pallecchi, L., Rossolini, G. M., & Bechi, P. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13127 · Cited by 139 · see citing works
Macke, L., Schulz, C., Koletzko, L., & Malfertheiner, P. (2020) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15604 · Cited by 118 · see citing works
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Paroni Sterbini, F., Palladini, A., Masucci, L., Cannistraci, C. V., Pastorino, R., Ianiro, G., Bugli, F., Martini, C., Ricciardi, W., Gasbarrini, A., et al. (2016) · Applied and Environmental Microbiology · doi:10.1128/aem.01437-16 · Cited by 108 · see citing works
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Kaakoush, N. O., Castaño-Rodríguez, N., Man, S. M., & Mitchell, H. M. (2015) · Trends in Microbiology · doi:10.1016/j.tim.2015.03.009 · Cited by 62 · see citing works
- Authors
- Amir, I., Konikoff, F. M., Oppenheim, M., Gophna, U., & Half, E. E.
- Affiliations
- Tel Aviv University (IL)
- Meir Medical Center (IL)
- Corresponding author
- Gophna, Uri
- Venue
- Environmental Microbiology
- Publisher
- Wiley
- Published
- 2013-10-22
- Volume
- 16
- Issue
- 9
- Pages
- 2905-2914
- ISSN
- 1462-2912 (ISSN-L)
- 1462-2920
- OpenAlex
- W1914460529
- Cited by
- 176
- References
- 37
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 16 · 2023: 18 · 2022: 12 · 2021: 23 · 2020: 20 · 2019: 14 · 2018: 14 · 2017: 11 · 2016: 9 · 2015: 15 · 2014: 6 · 2013: 1
- FWCI
- 9.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Environmental Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Israel Cancer Association
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Surgery › Helicobacter pylori-related gastroenterology studies
- Keywords
- gastric microbiota, esophagitis, Barrett's esophagus, proton pump inhibitors, gastroesophageal reflux, esophageal adenocarcinoma, Enterobacteriaceae, heartburn, dysplasia, metaplasia
- MeSH terms
- Bacteria, Barrett Esophagus, DNA, Bacterial, Esophagitis, Gastric Juice, Gastroesophageal Reflux, Humans, RNA, Ribosomal, 16S, Case-Control Studies, Sequence Analysis, DNA, Proton Pump Inhibitors, Microbiota
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