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. 2019 Feb;24(1):e12547.
doi: 10.1111/hel.12547. Epub 2018 Nov 15.

Evaluation of Gastric Microbiome and Metagenomic Function in Patients With Intestinal Metaplasia Using 16S rRNA Gene Sequencing

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Free PMC article

Evaluation of Gastric Microbiome and Metagenomic Function in Patients With Intestinal Metaplasia Using 16S rRNA Gene Sequencing

Chan Hyuk Park et al. Helicobacter. .
Free PMC article

Abstract

Background: Despite recent advances in studies on the gastric microbiome, the role of the non-Helicobacter pylori gastric microbiome in gastric carcinogenesis remains unclear. We evaluated the characteristics of the gastric microbiome and metagenomic functions in patients with IM.

Methods: Participants were classified into six groups according to disease status (chronic superficial gastritis [CSG], intestinal metaplasia [IM], and cancer) and H. pylori- infection status (H. pylori-positive and H. pylori-negative). The gastric microbiome was analyzed in mucosal tissues at the gastric antrum by 16S rRNA gene sequencing. Moreover, we assessed the metagenome including the type IV secretion system (T4SS) gene, as T4SS proteins are essential for transferring CagA from H. pylori- into the human gastric epithelium.

Results: Among the 138 included patients, 48, 9, 23, 14, 12, and 32 were classified into the H. pylori-negative CSG, H. pylori-negative IM, H. pylori-negative cancer, H. pylori-positive CSG, H. pylori-positive IM, and H. pylori-positive cancer groups, respectively. Cyanobacteria were predominant in the H. pylori-negative CSG group compared to in the H. pylori-negative IM and H. pylori-negative cancer groups (H. pylori-negative CSG vs H. pylori-negative IM vs H. pylori-negative cancer: 14.0% vs 4.2% vs 0.04%, P < 0.001). In contrast, Rhizobiales were commonly observed in the H. pylori-negative IM group (H. pylori-negative CSG vs H. pylori-negative IM vs H. pylori-negative cancer: 1.9% vs 15.4% vs 2.8%, P < 0.001). The relative abundance of Rhizobiales increased as H. pylori-infected stomachs progressed from gastritis to IM. In the H. pylori-negative IM group, genes encoding T4SS were prevalent among the metagenome. Additionally, after H. pylori- eradication therapy, the gastric microbiome was similar to the microbiome observed after spontaneous clearance of H. pylori-.

Conclusions: The relative abundance of Rhizobiales was higher in patients with H. pylori-negative IM than in those with H. pylori-negative CSG or cancer. Additionally, T4SS genes were highly observed in the metagenome of patients with IM. Highly abundant T4SS proteins in these patients may promote gastric carcinogenesis.

Keywords: Helicobacter pylori; gastric cancer; intestinal metaplasia; microbiome.

Conflict of interest statement

The authors disclose no potential conflict of interests.

Figures

Figure 1
Figure 1
Cladograms for bacterial abundance in the HP‐negative groups. (A) HP(−) CSG group, (B) HP(−) IM group, (C) HP(−) cancer group. Values represent the relative abundance of the specified bacterial taxa. Please refer to Appendix 1 for all detailed values of bacterial abundance. Clade marker size in the first and second inner circles represents the relative abundance of bacteria at the phylum and class levels, respectively. Height of the inner and outer rings represents the relative abundance of bacteria at the family and genus levels, respectively. CSG, chronic superficial gastritis; HP, Helicobacter pylori; IM, intestinal metaplasia
Figure 2
Figure 2
Principal component analysis plot. (A) CSG and IM groups, (B) All groups including cancer groups. A linear transition was identified in the HP(+) CSG group, followed by the HP(+) IM group and HP(−) IM group, as the relative abundance of HP decreased. Another linear transition was observed in the HP(−) CSG group, followed by the HP(−) IM group and HP(−) cancer group, mainly because of the decreased relative abundance of Cyanobacteria. CSG, chronic superficial gastritis; HP, Helicobacter pylori; IM, intestinal metaplasia
Figure 3
Figure 3
Highly identified genes encoding type IV secretion system protein subunits in the HP‐negative CSG and IM groups. Class A, B, and C represent the HP(−) CSG, HP(−) IM, and HP(−) cancer groups, respectively. Red bar graphs represent the relative abundance of genes in each sample. Solid and dotted lines in the bar graphs represent the mean and median values of relative abundance, respectively, in each group. All demonstrated genes had significant difference among the groups (P < 0.05 by the Kruskal‐Wallis test). CSG, chronic superficial gastritis; HP, Helicobacter pylori; IM, intestinal metaplasia; LDA, linear discriminant analysis
Figure 4
Figure 4
Relative abundance of HP, Rhizobiales, and Neisseriaceae in each sample of the HP(+) CSG, HP(+) IM, and HP(−) IM groups. The relative abundance of Rhizobiales and Neisseriaceae tended to gradually increase as the abundance of HP decreased. aSerum IgG anti‐HP antibody was evaluated via enzyme immunoassay. bHP infection was determined based on conventional methods including rapid urease test, urea breath test, and histologic examination. CSG, chronic superficial gastritis; HP, Helicobacter pylori; IM, intestinal metaplasia
Figure 5
Figure 5
Cladograms for bacterial abundance before and after HP eradication in the HP(+) CSG group. (A) Before eradication in the HP(+) CSG group, (B) After eradication in the HP(+) CSG group. Clade marker size in the first and second inner circles represents the relative abundance of bacteria at the phylum and class levels, respectively. Height of the inner and outer ring represents the relative abundance of bacteria at the family and genus levels, respectively. CSG, chronic superficial gastritis; HP, Helicobacter pylori

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References

    1. Chen S, Ying L, Kong M, Zhang Y, Li Y. The prevalence of Helicobacter pylori infection decreases with older age in atrophic gastritis. Gastroenterol Res Pract. 2013;2013:494783. - PMC - PubMed
    1. Chon HJ, Hyung WJ, Kim C, et al. Differential prognostic implications of gastric signet ring cell carcinoma: stage adjusted analysis from a single high‐volume Center in Asia. Ann Surg. 2017;265:946‐953. - PMC - PubMed
    1. Wong BC, Lam SK, Wong WM, et al. Helicobacter pylori eradication to prevent gastric cancer in a high‐risk region of China: a randomized controlled trial. JAMA. 2004;291:187‐194. - PubMed
    1. Shreiner AB, Kao JY, Young VB. The gut microbiome in health and in disease. Curr Opin Gastroenterol. 2015;31:69‐75. - PMC - PubMed
    1. Calmels S, Dalla Venezia N, Bartsch H. Isolation of an enzyme catalysing nitrosamine formation in Pseudomonas aeruginosa and Neisseria mucosae . Biochem Biophys Res Commun. 1990;171:655‐660. - PubMed

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