Oesophageal bacterial biofilm changes in gastro‐oesophageal reflux disease, Barrett's and oesophageal carcinoma: association or causality?
Open accessAbstract
Summary: Summary: Barrett's oesophagus (BO) and gastro‐oesophageal reflux disease (GERD) are precursors of oesophageal adenocarcinoma (OAC). There is an oesophageal biofilm, which changes in disease, but its role in aetiopathogenesis remains unclear. Aim: To define the oesophageal microbiota of patients with GERD, BO and OAC compared with controls and to investigate mucosal responses related to the microbiota. Methods: Cultural analysis identified the dominant bacterial species from a subset of each disease group. Based on this, molecular techniques were used to define the cohort. Host responses were analysed in tissues and co‐culture experiments. Results: A total of 111 species belonging to 26 genera were isolated. There was a significant decrease in bacterial counts in the GERD and BO groups for all genera except Campylobacter, which colonised GERD and Barrett's patients in increasing numbers. Campylobacter concisus was the dominant species. This relationship was not seen in the cancer group. Significant increases in IL‐18 were seen in GERD and BO colonised by Campylobacter. Conclusions: This study defines differences in the oesophageal biofilm in disease states, revealing the emergence of C. concisus as the dominant new colonist in the refluxed oesophagus. We also associate the presence of these bacteria with increased expression of cytokines related to carcinogenesis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Conventional treatment for non-erosive reflux disease with gastric acid suppressing medications has been associated with an increased incidence of abnormal microbiota and malignancy.
“In addition, the conventional treatment for non-erosive reflux disease with gastric acid suppressing medications has been associated with an increased incidence of abnormal microbiota and malignancy [10].”
From Cytoprotective Effects of Hydrogen Sulfide in Novel Rat Models of Non-Erosive Esophagitis (2014) · cites this paper as [10]
The Demographics section (page unavailable) reports no microbiological difference between patients prescribed PPIs and those not prescribed them. The Real-time PCR analysis likewise found no statistically significant difference by PPI exposure. The paper discusses microbiota changes with reflux-related disease, but does not link acid-suppressing treatment to increased malignancy. (LLM, conf=0.86)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredCampylobacter concisus could have a role in EAC, promoting the metaplastic processes in the early stages of cancer through an increase in IL-18 expression and downregulation of TGF-beta1, NF-κB and STAT3 signaling involved in the EAC cascade.
“This bacterium could have a role in EAC, promoting the metaplastic processes in the early stages of cancer through an increase in the interleukin (IL)-18 expression and downregulation of transforming growth factor beta 1, nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 signaling involved in the EAC cascade[42-44].”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [43]
In both ERD and BE, a significant enrichment of Campylobacter concisus has been reported.
“In both these conditions, a significant enrichment of Campylobacter concisus has been reported[42,43].”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [43]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Rising incidence of adenocarcinoma of the esophagus and gastric cardia
Blot, W. J. (1991) · JAMA · doi:10.1001/jama.265.10.1287 · Cited by 2,382 · 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
Microbial Colonization of the Upper Gastrointestinal Tract in Patients with Barrett's Esophagus
Macfarlane, S., Furrie, E., Macfarlane, G. T., & Dillon, J. F. (2007) · Clinical Infectious Diseases · doi:10.1086/518578 · Cited by 184 · see citing works
Self-citationAutomated systems for identification of microorganisms
Stager, C. E., & Davis, J. R. (1992) · Clinical Microbiology Reviews · doi:10.1128/cmr.5.3.302 · Cited by 158 · see citing works
Interleukin-18: biological properties and clinical implications.
Lebel‐Binay, S., Berger, A. K., Zinzindohoué, F., et al. (2000) · PubMed · Cited by 157 · see citing works
The Role of the Gastrointestinal Microbiota in Colorectal Cancer
Rowland, I. (2009) · Current Pharmaceutical Design · doi:10.2174/138161209788168191 · Cited by 129 · see citing works
Zheng, J., Meng, J., Zhao, S., et al. (2008) · Infection and Immunity · doi:10.1128/iai.01317-07 · Cited by 125 · see citing works
Bacterial biota in reflux esophagitis and Barrett’s esophagus
Pei, Z. (2005) · World Journal of Gastroenterology · doi:10.3748/wjg.v11.i46.7277 · Cited by 121 · see citing works
Nielsen, H. L., Nielsen, H., Ejlertsen, T., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023858 · Cited by 79 · see citing works
Kalischuk, L. D., & Inglis, G. D. (2011) · BMC Microbiology · doi:10.1186/1471-2180-11-53 · Cited by 68 · see citing works
Kaakoush, N. O., Deshpande, N., Wilkins, M. R., Tan, C. G., Burgos-Portugal, J. A., Raftery, M. J., Day, A. S., Lemberg, D. A., & Mitchell, H. M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0029045 · Cited by 68 · see citing works
Istivan, T. S., Coloe, P. J., Fry, B. N., et al. (2004) · Journal of Medical Microbiology · doi:10.1099/jmm.0.45554-0 · Cited by 59 · see citing works
Aabenhus, R. M., On, S. L. W., Siemer, B. L., Permin, H., & Andersen, L. P. (2005) · Journal of Clinical Microbiology · doi:10.1128/jcm.43.10.5091-5096.2005 · Cited by 56 · see citing works
Microbial flora in carcinoma of oesophagus.
Finlay, I., Wright, P. A., Menzies, T., et al. (1982) · Thorax · doi:10.1136/thx.37.3.181 · Cited by 42 · see citing works
Proinflammatory and antitumor properties of interleukin-18 in the gastrointestinal tract
Pagès, F., Berger, A. K., Lebel‐Binay, S., et al. (2000) · Immunology Letters · doi:10.1016/s0165-2478(00)00285-6 · Cited by 40 · see citing works
OESOPHAGEAL MICROBIAL FLORA IN CARCINOMA OF THE OESOPHAGUS
Lau, W. F., Wong, J., & Ong, K. (1981) · Australian and New Zealand Journal of Surgery · doi:10.1111/j.1445-2197.1981.tb05905.x · Cited by 38 · see citing works
The microflora of the oesophagus.
Mannell, A., Plant, M., & Frolich, J. (1983) · PubMed · Cited by 37 · see citing works
Serum interleukin-12 and interleukin-18 levels in patients with oesophageal squamous cell carcinoma.
Diakowska, D., Markocka-Mączka, K., Grabowski, K., et al. (2006) · PubMed · Cited by 32 · see citing works
Esophageal Bacteria and Barrett's Esophagus: A Preliminary Report
Osias, G. L., Bromer, M. Q., Thomas, R. M., Friedel, D. M., Miller, L. S., Suh, B., Lorber, B., Parkman, H. P., & Fisher, R. S. (2004) · Digestive Diseases and Sciences · doi:10.1023/b:ddas.0000017443.44802.4b · Cited by 31 · see citing works
Characterization ofCampylobacter concisushemolysins
Istivan, T. S., Smith, S. C., Fry, B. N., & Coloe, P. J. (2008) · FEMS Immunology & Medical Microbiology · doi:10.1111/j.1574-695x.2008.00467.x · Cited by 27 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
- [6]6. Pei Z, Yang L, Peek R, Levine SM, Pride DT, Blaser MJ. Bacterial biota in reflux oesophagitis and Barrett's oesophagus. World J Gastroenterol 2005; 11: 7277-83.
- [12]12. Olson WP, ed. ]Automated Microbial Identification and Quantitation. Buffalo Grove, IL: Interpharm Press, 1996.
- [17]17. Istivan TS, Smith SC, Fry BN, Coloe PJ. Characterisation of Campylobacter concisus hemolysins. FEMS Immunol Med Microbiol 2008; 54: 224-35.
- [22]22. Zheng J, Meng J, Zhao S, Singh R, Song W. Campylobacter-induced interleukin secretion in polarised human epitelial calles requires Campylobacter secreted cytolethal distending toxin and toll like receptor mediated activation of NF- kappaB. Infect Immun 2008; 76: 4498-508.
Cited by
Sorted by citations
Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified
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
The esophageal microbiota in health and disease
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
Is Campylobacter to esophageal adenocarcinoma as Helicobacter is to gastric adenocarcinoma?
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
Cytoprotective Effects of Hydrogen Sulfide in Novel Rat Models of Non-Erosive Esophagitis
Zayachkivska, O., Havryluk, O., Hrycevych, N., Bula, N., Grushka, O., & Wallace, J. L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0110688 · Cited by 34 · see citing works
“In addition, the conventional treatment for non-erosive reflux disease with gastric acid suppressing medications has been associated with an increased incidence of abnormal microbiota and malignancy [10].”
BackgroundThe microbiome as a potential biomarker for oesophageal adenocarcinoma
Abrams, J. A. (2017) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(16)30177-7 · Cited by 7 · see citing works
- Authors
- Blackett, K. L., Siddhi, S. S., Cleary, S., Steed, H., Miller, M. H., Macfarlane, S., Macfarlane, G. T., & Dillon, J. F.
- Affiliations
- University of Dundee (GB)
- Corresponding author
- Dillon, J. F.
- Venue
- Alimentary Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2013-04-22
- Volume
- 37
- Issue
- 11
- Pages
- 1084-1092
- ISSN
- 0269-2813 (ISSN-L)
- 1365-2036
- OpenAlex
- W1967071879
- Cited by
- 211
- References
- 21
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 20 · 2023: 20 · 2022: 17 · 2021: 33 · 2020: 18 · 2019: 18 · 2018: 15 · 2017: 21 · 2016: 13 · 2015: 7 · 2014: 6 · 2013: 1
- FWCI
- 8.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Alimentary Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Funders
- Royal Society
- Royal Society of Edinburgh
- Topics
- Health Sciences › Medicine › Surgery › Esophageal Cancer Research and Treatment
- Health Sciences › Medicine › Surgery › Helicobacter pylori-related gastroenterology studies
- Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
- Keywords
- gastroesophageal reflux disease, Barrett's esophagus, esophageal adenocarcinoma, Campylobacter concisus, Campylobacter, IL-18, cytokines, carcinogenesis, bacterial colonization
- MeSH terms
- Adenocarcinoma, Adult, Aged, Aged, 80 and over, Barrett Esophagus, Esophageal Neoplasms, Esophagus, Female, Gastroesophageal Reflux, Humans, Male, Middle Aged, RNA, Messenger, Colony Count, Microbial, Cohort Studies, Case-Control Studies, Cytokines, Bacterial Physiological Phenomena, Biofilms, Coculture Techniques, Metagenome, Young Adult, Real-Time Polymerase Chain Reaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
