Determination of the Roles of <i>H. pylori</i> Outer Membrane Virulence Factors and Pyroptosis-Associated NLRP3, ASC, Caspase-1, Gasdermin D, IL-1β and IL-18 in Ulcer and Gastritis Pathogenesis

Objective: We aimed to investigate the association between pyroptosis and the outer membrane virulence factor of H. pylori in patients with gastritis and ulcers. Methods: DNA, RNA, and protein were extracted from a single tissue sample taken from the antrum region of the stomach of volunteer patients. The expression of bacterial outer membrane virulence genes in these tissues was analyzed at the gene level, and the expression levels of major pyroptosis markers were compared between H. pylori-infected and uninfected ulcer and gastritis patient groups. Results: Results showed that infection by H. pylori induced alterations in the expression levels of ASC, NLRP3, caspase-1, GSDMD, IL-18, and IL-1β, suggesting an association between pyroptosis markers and gastritis or ulcers related to H. pylori. Statistically significant variations in the correlations between increased levels of target markers and active caspase-1 across different patient cohorts demonstrated the effective detection of pyroptosis. Both pro and active forms of caspase-1, GSDMD, IL-18, and IL-1β were evaluated within the sample, leading to the identification of patients displaying indications of pyroptosis. The vacA m2 allele, which elicits a significant and contrasting ASC response in individuals with gastritis and ulcer, along with its increased prevalence and GSDMD upregulation in ulcerative conditions, in conjunction with the babB gene, are crucial for comprehending the interplay between the virulence determinants of H. pylori and pyroptosis in bacteria-associated pathologies. These findings underscore a deficiency in the current body of literature. Conclusion: This study holds considerable importance as it represents the first examination of the interrelation between pathogen virulence factors and pyroptosis in diseases associated with H. pylori. Grasping this interrelationship is vital for elucidating the intracellular alterations induced by H. pylori, and its pathogenicity, and for the development of novel targeted therapeutic interventions.