Integrated Analysis of Virulence, Antimicrobial Resistance, and Gastric Mucosal Phenotype in Helicobacter pylori from a High-Risk Mongolian Population

Mongolia has one of the highest gastric cancer burdens worldwide, yet integrated data linking Helicobacter pylori virulence, antimicrobial resistance (AMR), and gastric mucosal phenotype remain limited, particularly in ethnically distinct populations such as Bayan-Ölgii. We conducted a prospective single-center study of patients undergoing upper gastrointestinal endoscopy, with mucosal assessment using the Kyoto classification and histological scoring based on the Updated Sydney System. H. pylori isolates were cultured, antimicrobial susceptibility was determined by agar dilution, and whole-genome sequencing of 43 isolates enabled analysis of virulence-associated genes, antimicrobial resistance determinants, and population structure. Among 107 patients, H. pylori infection was associated with higher Kyoto scores than in uninfected individuals (4.39 vs. 3.42, p = 0.01). Major virulence-associated determinants were widely distributed: cagA was detected in 81.4% of isolates, and all interpretable cagA-positive isolates carried Western-type EPIYA architectures. Among 10 predefined virulence markers evaluated in age- and sex-adjusted models, hopQ Type I and vacA d1 were associated with higher Kyoto scores, whereas vacA i1 was associated with lower Kyoto scores; all three associations remained significant after Benjamini–Hochberg false discovery rate correction. Phenotypic antimicrobial resistance among 34 isolates with available susceptibility data was observed for metronidazole (58.8%), clarithromycin (35.3%), amoxicillin (29.4%), levofloxacin (20.6%), and minocycline (2.9%). Whole-genome sequencing identified established resistance determinants for clarithromycin, levofloxacin, and metronidazole, together with additional resistance-associated or uncertain variants, particularly for metronidazole and amoxicillin. Population genomic analysis demonstrated heterogeneous ancestry, with most isolates showing affinity with hpNorthAsia and smaller subsets with hspAltai and other Eurasian-related lineages. These findings demonstrate substantial heterogeneity in antimicrobial resistance and genomic background, while specific virulence-associated genotypes were associated with variation in gastric mucosal phenotype. The heterogeneous, antibiotic-specific distribution of phenotypic resistance and genomic resistance-associated findings highlights the importance of locally informed antimicrobial strategies in Mongolia.