Abstract / Summary
Helicobacter pylori is a major cause of gastric cancer and has also been linked to extra-gastric cancers, including cholangiocarcinoma (CCA). In northeastern Thailand, where Opisthorchis viverrini is endemic, co-infection with H. pylori may promote hepatobiliary carcinogenesis. However, the genomic features and virulence potential of H. pylori strains circulating in these settings remain poorly understood. Whole-genome sequencing generated 14 genome datasets from 12 H. pylori isolates from individuals living in O. viverrini -endemic communities in northeastern Thailand. De novo genome assembly, average nucleotide identity (ANI), and whole-genome SNP-based phylogenetic analyses were conducted against 2,293 globally representative H. pylori genomes. Virulence profiling focused on cagA genotypes, EPIYA and CM motifs, and SNP variation in key pathogenic and metabolic genes. Phylogenomic and ANI analyses showed that most Thai isolates clustered with Southeast Asian strains, with close relationships to East Asian and Oceanian lineages. All 14 isolates carried cagA , displaying Western-type (ABC), East Asian-type (ABD), and non-canonical EPIYA motif patterns. Comparative SNP analysis identified conserved mutations in cagA , trpD , and hpaA , as well as regional variants in virulence, metabolic, and secretion-associated genes. These findings highlight the genomic diversity and adaptive evolution of H. pylori in liver fluke-endemic areas and suggest strain-specific adaptations may contribute to gastrointestinal and hepatobiliary carcinogenesis during chronic parasitic co-infection.