- The hpEastAsia strain of Helicobacter pylori is a major phylogenetic population of this gram-negative, spiral-shaped bacterium, identified through multi-locus sequence typing (MLST).
- Prevalent in East Asian countries such as China, Japan, and Korea, as well as parts of Southeast Asia, hpEastAsia is notable for its strong association with high gastric cancer rates in these regions. This population reflects the co-evolution of H. pylori with human populations in East Asia, likely originating from ancient migrations from Central Asia and subsequent adaptation to local hosts.
- hpEastAsia is genetically distinct from other populations like hpEurope, hpAfrica1, or hpNEAfrica, and its high virulence makes it a critical strain for studying the molecular mechanisms of H. pylori-associated diseases, particularly gastric cancer, which is a leading cause of cancer mortality in East Asia.
- Genetically, hpEastAsia is characterized by unique allele combinations that form a distinct clade in phylogenetic analyses, reflecting its divergence from other H. pylori populations. Most hpEastAsia strains possess the cag pathogenicity island (cagPAI), which encodes the cagA gene and a type IV secretion system (T4SS) that injects CagA into host gastric epithelial cells, triggering intense inflammation and increasing the risk of peptic ulcers and gastric cancer. Unlike hpEurope’s Western-type cagA EPIYA motifs (ABC-type), hpEastAsia strains typically feature East Asian-type EPIYA motifs (ABD-type), which are more oncogenic due to stronger binding to SHP-2, a key signaling molecule in carcinogenesis. The vacA gene in hpEastAsia commonly presents as the s1m1 allele, which is highly toxic and strongly associated with severe pathology, with minimal presence of less toxic s1m2 or s2m2 alleles. The dupA gene, linked to duodenal ulcer risk, is present in some hpEastAsia strains but less consistently than in hpAfrica2. High recombination rates and adaptation to East Asian host populations contribute to hpEastAsia’s genetic diversity, making it a focal point for genomic studies.
- In terms of pathogenicity, hpEastAsia strains are strongly linked to severe gastric diseases, particularly gastric cancer, which distinguishes East Asia from regions with lower cancer rates, such as Africa (the “African enigma”). In countries like Japan and Korea, where H. pylori prevalence ranges from 40–70%, hpEastAsia strains drive high incidences of gastric cancer, with East Asian countries accounting for a significant proportion of global cases. The cagA ABD-type motifs and vacA s1m1 genotypes in hpEastAsia enhance proinflammatory and carcinogenic pathways, contributing to higher rates of atrophic gastritis, intestinal metaplasia, and adenocarcinoma compared to hpEurope or hpAfrica1. Host genetic factors, such as polymorphisms in IL-1β and TNF-α, further amplify inflammatory responses in East Asian populations, exacerbating disease severity. Peptic ulcers are also common, though gastric cancer remains the most significant clinical concern. Environmental factors, including high-salt diets and smoking, synergize with hpEastAsia’s virulence to elevate cancer risk.
- Antibiotic resistance in hpEastAsia strains is a major challenge, driven by widespread antibiotic use in East Asia. Clarithromycin resistance, often linked to A2143G and A2142G mutations, is alarmingly high, ranging from 20–50% in countries like China and Japan, rendering standard triple therapies (clarithromycin, amoxicillin, proton pump inhibitor) increasingly ineffective. Metronidazole resistance is also prevalent (40–70%), while amoxicillin resistance remains relatively low (<10%) but is rising. Fluoroquinolone resistance, driven by gyrA mutations, affects 20–30% of isolates, and tetracycline resistance is emerging in some areas. In response, bismuth quadruple therapy and sequential or concomitant regimens are increasingly recommended in East Asia. The high resistance rates in hpEastAsia strains necessitate routine antimicrobial susceptibility testing, though access to such testing varies across the region, complicating treatment strategies.
- In research, hpEastAsia is pivotal for understanding the molecular basis of H. pylori-associated gastric cancer and the evolutionary history of the bacterium. Its genetic distinctiveness and high virulence provide a model for studying host-pathogen interactions, particularly the role of cagA EPIYA motifs and vacA alleles in carcinogenesis. Comparative genomic studies with hpEurope, hpAfrica1, and hpNEAfrica highlight hpEastAsia’s unique adaptations, such as its oncogenic cagA ABD-type, which explain the elevated gastric cancer burden in East Asia. The strain’s association with human migrations, linking East Asian populations to Central Asian ancestors, supports its use in tracing ancient human movements. hpEastAsia is also a focus for developing targeted interventions, including vaccines and novel therapeutics, to address the high disease burden in East Asia. Its clinical and evolutionary significance makes hpEastAsia a cornerstone of H. pylori research, informing global health strategies and personalized medicine approaches.
