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Background <p>East Asian <i>Helicobacter pylori</i> (<i>H. pylori</i>) strains are commonly classified as a single hspEAsia lineage characterized by elevated virulence. However, gastric cancer incidence varies markedly across China, suggesting that clinically relevant bacterial heterogeneity may exist within this framework. A systematic assessment of fine-scale population structure and its functional correlates in Chinese <i>H. pylori</i> remained limited.</p> Methods <p>We analyzed whole-genome sequencing data from 1,243 <i>H. pylori</i> isolates collected from 20 provinces and regions across China, including 50 newly sequenced clinical strains from Shanghai. Fine-scale population structure was resolved using coancestry–based clustering and chromosome painting. Subpopulations were further characterized by pangenome composition, virulence factor repertoires, genome-wide fixation index (Fst), and predicted antibiotic resistance–associated mutations. E-test minimum inhibitory concentration (MIC) assays were performed to compare phenotypic susceptibility with mutation-based resistance prediction.</p> Results <p>Six geographically structured subpopulations were identified within Chinese hspEAsia. SubtypeCentral represented a widely distributed mainland lineage, whereas subpopulations from Inner Mongolia and Taiwan showed the greatest genetic divergence. Chromosome painting revealed strong within-lineage ancestry cohesion in SubtypeTaiwan, contrasted by extensive admixture in Inner Mongolia and Yunnan. Recurrent high-Fst loci across subpopulations, including <i>glnA</i>, <i>frpB4</i>, and <i>HP1501</i>, highlighted genomic regions contributing disproportionately to population differentiation. Marked heterogeneity in virulence profiles was observed. SubtypeInnerMongolia showed a higher prevalence of <i>cagA</i>-negative or Western-type <i>cagA</i> variants and a reduced overall repertoire of virulence genes. Predicted antibiotic resistance patterns were also strongly subtype dependent. Notably, SubtypeTaiwan exhibited an exceptionally high rifampicin resistance rate driven almost exclusively by a single <i>rpoB</i> A2414V mutation. E-test validation in the newly collected isolates provided supportive phenotypic evidence for the mutation-based resistance strategy.</p> Conclusions <p>Chinese <i>H. pylori</i> hspEAsia strains comprise multiple regionally structured subpopulations with distinct evolutionary histories, gene content, virulence profiles, and predicted resistance determinants. This fine-scale genomic classification provides a biological basis for understanding regional disparities in gastric cancer risk and genotypic resistance, and supports the need for subtype-aware surveillance and region-specific clinical management strategies in China.</p>

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Genomic landscape and fine-scale population structure of Helicobacter pylori across China

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月16日

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  • Yi Dou,
  • Pengfei Kong,
  • Mingzhu Huang,
  • Yonghu Xu,
  • Jingyu Guo,
  • Yong Xie,
  • Xiaohua Jiang,
  • Yantao Duan,
  • Gonghong Wei,
  • Dazhi Xu

摘要

Background

East Asian Helicobacter pylori (H. pylori) strains are commonly classified as a single hspEAsia lineage characterized by elevated virulence. However, gastric cancer incidence varies markedly across China, suggesting that clinically relevant bacterial heterogeneity may exist within this framework. A systematic assessment of fine-scale population structure and its functional correlates in Chinese H. pylori remained limited.

Methods

We analyzed whole-genome sequencing data from 1,243 H. pylori isolates collected from 20 provinces and regions across China, including 50 newly sequenced clinical strains from Shanghai. Fine-scale population structure was resolved using coancestry–based clustering and chromosome painting. Subpopulations were further characterized by pangenome composition, virulence factor repertoires, genome-wide fixation index (Fst), and predicted antibiotic resistance–associated mutations. E-test minimum inhibitory concentration (MIC) assays were performed to compare phenotypic susceptibility with mutation-based resistance prediction.

Results

Six geographically structured subpopulations were identified within Chinese hspEAsia. SubtypeCentral represented a widely distributed mainland lineage, whereas subpopulations from Inner Mongolia and Taiwan showed the greatest genetic divergence. Chromosome painting revealed strong within-lineage ancestry cohesion in SubtypeTaiwan, contrasted by extensive admixture in Inner Mongolia and Yunnan. Recurrent high-Fst loci across subpopulations, including glnA, frpB4, and HP1501, highlighted genomic regions contributing disproportionately to population differentiation. Marked heterogeneity in virulence profiles was observed. SubtypeInnerMongolia showed a higher prevalence of cagA-negative or Western-type cagA variants and a reduced overall repertoire of virulence genes. Predicted antibiotic resistance patterns were also strongly subtype dependent. Notably, SubtypeTaiwan exhibited an exceptionally high rifampicin resistance rate driven almost exclusively by a single rpoB A2414V mutation. E-test validation in the newly collected isolates provided supportive phenotypic evidence for the mutation-based resistance strategy.

Conclusions

Chinese H. pylori hspEAsia strains comprise multiple regionally structured subpopulations with distinct evolutionary histories, gene content, virulence profiles, and predicted resistance determinants. This fine-scale genomic classification provides a biological basis for understanding regional disparities in gastric cancer risk and genotypic resistance, and supports the need for subtype-aware surveillance and region-specific clinical management strategies in China.