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. 2024 Jan 7;30(1):91-107.
doi: 10.3748/wjg.v30.i1.91.

Mechanistic research: Selenium regulates virulence factors, reducing adhesion ability and inflammatory damage of Helicobacter pylori

Chun Qin  1   2 , Gan-Rong Huang  1   3 , Ai-Xing Guan  1   2 , Wen-Ting Zhou  1   3 , Hao Chen  4 , Pei-Pei Luo  5 , Xian-Ke Luo  6 , Yan-Qiang Huang  1   3 , Zan-Song Huang  1   7
Affiliations

Mechanistic research: Selenium regulates virulence factors, reducing adhesion ability and inflammatory damage of Helicobacter pylori

Chun Qin et al. World J Gastroenterol. .

Abstract

Background: The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host. Although selenium is closely related to pathogenicity as an environmental factor, the specific correlation between them remains unclear.

Aim: To investigate how selenium acts on virulence factors and reduces their toxicity.

Methods: H. pylori strains were induced by sodium selenite. The expression of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin gene A (VacA) was determined by quantitative PCR and Western blotting. Transcriptomics was used to analyze CagA, CagM, CagE, Cag1, Cag3, and CagT. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction, and H. pylori colonization, inflammatory reactions, and the cell adhesion ability of H. pylori were assessed.

Results: CagA and VacA expression was upregulated at first and then downregulated in the H. pylori strains after sodium selenite treatment. Their expression was significantly and steadily downregulated after the 5th cycle (10 d). Transcriptome analysis revealed that sodium selenite altered the levels affect H. pylori virulence factors such as CagA, CagM, CagE, Cag1, Cag3, and CagT. Of these factors, CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite. Moreover, CagT expression was upregulated before the 3rd cycle (6 d) and significantly downregulated after the 5th cycle. Cag1 and Cag3 expression was upregulated and downregulated, respectively, but no significant change was observed by the 5th cycle. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction. The extent of H. pylori colonization in the stomach increased; however, sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H. pylori-infected mice, and the cell adhesion ability of H. pylori was significantly weakened.

Conclusion: These results demonstrate that H. pylori displayed virulence attenuation after the 10th d of sodium selenite treatment. Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H. pylori, thus mitigating the inflammatory damage to the gastric mucosa.

Keywords: Adherence; Helicobacter pylori; Inflammation; Sodium selenite; Virulence factors.

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Conflict of interest statement

Conflict-of-interest statement: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Induction of Helicobacter pylori with sodium selenite downregulates cytotoxin-associated protein A and vacuolating cytotoxin gene A expression. A: Effect of induction of the Hp G27 strain with sodium selenite on cytotoxin-associated protein A (CagA) for 1-6 cycles; B: Effect of induction of the Hp G27 strain with sodium selenite on vacuolating cytotoxin gene A (VacA) for 1-6 cycles; C-E: Effect of induction of the Hp G27 strain with sodium selenite on the CagA and VacA proteins for 1, 3, and 6 cycles; F: Effect of induction of the Hp G27 strain with 4 mol/L sodium selenite on CagA and VacA of the NSH57 strain for 6 cycles; G and H: Effect of induction of the NSH57 strain with 4 μmol/L sodium selenite on CagA and VacA protein. aP < 0.05; bP < 0.01.
Figure 2
Figure 2
Effect of sodium selenite on the Helicobacter pylori transcriptome. A: Half inhibitory concentration of sodium selenite given to Helicobacter pylori; B: RNA sequencing correlation examination; C: Principal component analysis of the transcriptome; D: The Venn diagram of differentially expressed genes (DEGs); E: Cluster analysis of DEGs; F-H: Gene set enrichment analysis of DEGs between treatment groups; I: Epithelial cell signal transduction pathways associated with H. pylori infection.
Figure 3
Figure 3
Verification of differentially expressed genes and changes in screened differentially expressed genes following induction. A: Quantitative PCR verification of differentially expressed genes (DEGs); B-F: Changes in DEGs after induction with 4 μmol/L sodium selenite for 1-5 cycles. aP < 0.05; bP < 0.01.
Figure 4
Figure 4
Induction with sodium selenite decreased the adhesion ability of Helicobacter pylori strains. A: Number of cells adhering to Helicobacter pylori strains was determined using a fluorescence microscope; B: Number of cells adhering to H. pylori strains was determined with the SYTO 9 stain. aP < 0.05; bP < 0.01; cP < 0.05.
Figure 5
Figure 5
Induction with sodium selenite decreased Helicobacter pylori-induced inflammation. A-C: Expression of IL-1β (A), IL-6 (B), and TNF-α (C) in Helicobacter pylori-infected mice after induction; D: Gastric mucosal inflammation in mice with acute gastritis; E: H. pylori colonization in the stomach of mice with acute gastritis. aP < 0.05; bP < 0.01; cP < 0.05; dP < 0.01; eP < 0.05; fP < 0.01; hP < 0.01.
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