Microbiome Analysis in Gastric Intestinal Metaplasia and in Gastric Cancer and Subtypes Correlation
NCT ID: NCT04365946
Last Updated: 2020-04-28
Study Results
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Basic Information
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UNKNOWN
80 participants
OBSERVATIONAL
2020-04-18
2023-05-15
Brief Summary
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Our intention is to further analyze the microbiome based on histological types. Most studies on stomach cancer have focused on the microbiota of gastric microbiota. Recent data have shown that the microbiome of the small intestine, especially the mucosa, can play a key role in the condition of the gastrointestinal tract. Disturbance of the microbiome of the small intestine has been found in celiac disease, chronic liver disease, diabetes and irritable bowel syndrome. However, information on the role of the microbiome in IM remains limited.
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Detailed Description
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These guidelines emphasize the increased risk of cancer in patients with gastric atrophy and IM and the need for staging in cases of high-grade dysplasia. Risk factors for IM include Helicobacter pylori infection, high NaCl intake, smoking, alcohol consumption and chronic biliary reflux.
The development of intestinal-type gastric carcinoma occurs in four stages: non-atrophic gastritis, multifocal atrophic gastritis, IM, and dysplasia. The IM of the gastric cardia and the Barrett's esophagus differ in the risk of malignancy. Elevated serum pepsinogen levels have been suggested as an indicator of extensive gastric atrophy. Currently, there are no reliable markers of gastric dysplasia or gastric cancer.
Based on the available data, it appears that the IM of the gastric cardia is a possible precursor to the development of intestinal-type carcinoma of the stomach. It has been found that 45% of patients with gastric carcinoma had residual IM, supporting the idea that IM is a particularly important precursor to its development. Histologically, the IM may be complete or incomplete. Complete (type I) intestinal metaplasia is defined by the mucosa of the small intestinal type with mature absorbent cells, cell cups, and a brush-like outline. Incomplete intestinal metaplasia (type II) secretes cialomycin and is similar to colonic epithelium with columns of "intermediate" cells at various stages of differentiation, irregular mucosal droplets and the absence of a "brush" limit. The highest risk of gastric cancer is associated with incomplete and / or extensive IM.
Recent studies show that microbial changes are related to the histological stages of gastric oncogenesis. Chronic H. pylori infection can cause inflammation of the mucosa and cause histological changes. It is also recognized as an important risk factor for GC. However, only 3% of patients infected with H. pylori develop GC. In addition, H. pylori has been found to be usually undetectable in GC samples. These studies suggest that H. pylori infection may only be an early event for the gastric mucosa, which will undergo further oncogenic changes and indicate the possible role of mucosal microbes, with the exception of H. pylori in the gastric carcinoma.
The dominant germ type in the gastric mucosa was found to be protein-secreted bacteria, in both H. pylori negative and positive for H. pylori samples. Two previous studies have shown that the microbial count in IM patients was found to be partially overlapped with the group of gastritis and cancer among patients with H. pylori infection. Li et al (2017) found that the microbial amount in gastritis samples overlapped mostly with that of IM samples. In contrast, the microflora of patients with IM and GC had significantly lower microbial richness, while the biodiversity of the microbiology of patients with overt gastritis (EG), chronic gastritis (CG) and IM was similar in total, with the exception of those with GC. These conflicting results suggest that IM may be the key point in microbial change and that there may be other qualitative factors involved in gastric oncogenesis, especially in patients with IM.
Research subject and objectives The study will be performed on patients undergoing gastroscopy who have IM and / or GC findings. In patients with IM, the microbiome will be analyzed and correlated with the type of IM (complete-incomplete). The same will be done for patients with GC (intestinal-type cancer).
Thematic area The aim of the study will be to analyze the microbiome in the blood and stomach in patients with intestinal metaplasia (IM) and / or gastric cancer (GC). As far as IM is concerned, it has been found that the incomplete type is related to GC mainly intestinal-type. Studies show differences in the microbiome in patients with IM and in patients with GC, but do not specify whether these differences are related to histological types.
Our intention is to further analyze the microbiome based on histological types. Most studies on stomach cancer have focused on the microbiota of gastric microbiota. Recent data have shown that the microbiome of the small intestine, especially the mucosa, can play a key role in the condition of the gastrointestinal tract. Disturbance of the microbiome of the small intestine has been found in celiac disease, chronic liver disease, diabetes and irritable bowel syndrome. However, information on the role of the microbiome in IM remains limited.
Keywords Gastric intestinal metaplasia, Complete Type, Incomplete Type, Gastric Cancer, Microbiome
Conditions
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Study Design
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CASE_CONTROL
PROSPECTIVE
Study Groups
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Complete type
Patients with complete-type intestinal metaplasia
Gastroscopy
Upper GI endoscopy and biopsy
Incomplete type
Patients with incomplete-type intestinal metaplasia
Gastroscopy
Upper GI endoscopy and biopsy
Controls
Healthy subjects
Gastroscopy
Upper GI endoscopy and biopsy
Interventions
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Gastroscopy
Upper GI endoscopy and biopsy
Eligibility Criteria
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Inclusion Criteria
* Healthy controls
Exclusion Criteria
* IBD
* Autoimmune diseases
* Otherwise tumours
18 Years
75 Years
ALL
Yes
Sponsors
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University of Ioannina
OTHER
University Hospital, Ioannina
OTHER
Responsible Party
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George Pappas-Gogos
George Pappas-Gogos, Principal Investigator
Principal Investigators
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Konstantinos Vlachos, Prof
Role: STUDY_DIRECTOR
University of Ioannina
George Pappas-Gogos, Dr
Role: PRINCIPAL_INVESTIGATOR
University Hospital, Ioannina
Locations
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University Hospital of Ioannina
Ioannina, , Greece
Countries
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References
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Gao JJ, Zhang Y, Gerhard M, Mejias-Luque R, Zhang L, Vieth M, Ma JL, Bajbouj M, Suchanek S, Liu WD, Ulm K, Quante M, Li ZX, Zhou T, Schmid R, Classen M, Li WQ, You WC, Pan KF. Association Between Gut Microbiota and Helicobacter pylori-Related Gastric Lesions in a High-Risk Population of Gastric Cancer. Front Cell Infect Microbiol. 2018 Jun 19;8:202. doi: 10.3389/fcimb.2018.00202. eCollection 2018.
Liu X, Shao L, Liu X, Ji F, Mei Y, Cheng Y, Liu F, Yan C, Li L, Ling Z. Alterations of gastric mucosal microbiota across different stomach microhabitats in a cohort of 276 patients with gastric cancer. EBioMedicine. 2019 Feb;40:336-348. doi: 10.1016/j.ebiom.2018.12.034. Epub 2018 Dec 21.
Wang L, Zhou J, Xin Y, Geng C, Tian Z, Yu X, Dong Q. Bacterial overgrowth and diversification of microbiota in gastric cancer. Eur J Gastroenterol Hepatol. 2016 Mar;28(3):261-6. doi: 10.1097/MEG.0000000000000542.
Gong J, Li L, Zuo X, Li Y. Change of the duodenal mucosa-associated microbiota is related to intestinal metaplasia. BMC Microbiol. 2019 Dec 9;19(1):275. doi: 10.1186/s12866-019-1666-5.
Eun CS, Kim BK, Han DS, Kim SY, Kim KM, Choi BY, Song KS, Kim YS, Kim JF. Differences in gastric mucosal microbiota profiling in patients with chronic gastritis, intestinal metaplasia, and gastric cancer using pyrosequencing methods. Helicobacter. 2014 Dec;19(6):407-16. doi: 10.1111/hel.12145. Epub 2014 Jul 23.
Park CH, Lee AR, Lee YR, Eun CS, Lee SK, Han DS. Evaluation of gastric microbiome and metagenomic function in patients with intestinal metaplasia using 16S rRNA gene sequencing. Helicobacter. 2019 Feb;24(1):e12547. doi: 10.1111/hel.12547. Epub 2018 Nov 15.
Hsieh YY, Tung SY, Pan HY, Yen CW, Xu HW, Lin YJ, Deng YF, Hsu WT, Wu CS, Li C. Increased Abundance of Clostridium and Fusobacterium in Gastric Microbiota of Patients with Gastric Cancer in Taiwan. Sci Rep. 2018 Jan 9;8(1):158. doi: 10.1038/s41598-017-18596-0.
Park CH, Lee JG, Lee AR, Eun CS, Han DS. Network construction of gastric microbiome and organization of microbial modules associated with gastric carcinogenesis. Sci Rep. 2019 Aug 27;9(1):12444. doi: 10.1038/s41598-019-48925-4.
Jencks DS, Adam JD, Borum ML, Koh JM, Stephen S, Doman DB. Overview of Current Concepts in Gastric Intestinal Metaplasia and Gastric Cancer. Gastroenterol Hepatol (N Y). 2018 Feb;14(2):92-101.
Schulz C, Schutte K, Mayerle J, Malfertheiner P. The role of the gastric bacterial microbiome in gastric cancer: Helicobacter pylori and beyond. Therap Adv Gastroenterol. 2019 Dec 18;12:1756284819894062. doi: 10.1177/1756284819894062. eCollection 2019.
Cui J, Cui H, Yang M, Du S, Li J, Li Y, Liu L, Zhang X, Li S. Tongue coating microbiome as a potential biomarker for gastritis including precancerous cascade. Protein Cell. 2019 Jul;10(7):496-509. doi: 10.1007/s13238-018-0596-6. Epub 2018 Nov 26.
Other Identifiers
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1
Identifier Type: -
Identifier Source: org_study_id
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