- Helicobacter pylori is a genetically diverse, spiral-shaped bacterium that colonizes the human gastric mucosa. It is associated with a range of diseases, including chronic gastritis, peptic ulcer disease, and gastric adenocarcinoma.
- Despite infecting more than half of the world’s population, the clinical outcomes of H. pylori infection vary significantly across regions. A major contributor to this variability is the bacterium’s extensive genetic diversity and its structured global population, shaped over tens of thousands of years through its co-evolution with humans.
- Advances in multilocus sequence typing (MLST) and whole-genome sequencing have revealed that H. pylori comprises several geographically and genetically distinct populations. These include hpAfrica1, hpAfrica2, hpNEAfrica, hpEurope, hpAsia2, hpEastAsia, and hpSahul. Each of these lineages corresponds to a specific geographic region and human population, and their distribution closely mirrors ancient human migration routes. For example, hpEurope, which predominates in Europe and the Middle East, is a hybrid population formed through the recombination of ancestral African and Asian strains. In contrast, hpEastAsia, found in East Asian populations, is more clonal and has evolved distinct virulence profiles, while hpAfrica2 represents one of the most ancient and divergent lineages, restricted primarily to southern Africa.
- The co-evolution of H. pylori with humans is one of the most well-documented examples of host-microbe association. As early modern humans migrated out of Africa, H. pylori accompanied them, adapting to new environments and host genetic backgrounds. This long-standing association has allowed H. pylori to serve as a marker for tracing ancient human movements. For instance, the discovery of the hpSahul population in Aboriginal Australians and Papuans reflects one of the earliest migrations into Oceania, more than 30,000 years ago. Similarly, the distinctiveness of hpNEAfrica highlights the historical isolation of populations in the Horn of Africa.
- The clinical significance of these lineages lies in their differing virulence factor repertoires. The cagA gene, which encodes the cytotoxin-associated gene A protein, varies between populations. The East Asian-type CagA (with the EPIYA-D motif), common in hpEastAsia strains, is more strongly associated with gastric cancer than the Western-type (EPIYA-C) found in hpEurope. Likewise, vacA, another major virulence gene, shows allelic variation (e.g., s1/m1 versus s2/m2) that affects toxin activity and host immune modulation. These differences in virulence factor profiles contribute to the observed disparities in disease outcomes across populations. For instance, regions with high prevalence of hpEastAsia strains, such as Japan and Korea, also report high gastric cancer incidence. Conversely, despite high rates of infection in Africa, particularly with hpAfrica1 strains, gastric cancer rates remain relatively low—a paradox known as the “African enigma.”
- Understanding the population structure of H. pylori has important implications for both research and public health. Lineage-specific differences in virulence, antibiotic resistance, and immune interactions can inform the development of targeted diagnostics, vaccines, and therapies. Furthermore, knowledge of the regional distribution of H. pylori populations enhances epidemiological surveillance and supports efforts to implement precision medicine strategies in gastroenterology. For evolutionary biologists and anthropologists, the study of H. pylori offers a unique microbial perspective on human history and migration.
- In conclusion, the phylogeographic lineages of H. pylori encapsulate the deep evolutionary relationship between this bacterium and its human host. These populations not only influence disease outcomes but also provide valuable insights into human ancestry and global population dynamics. Continued research into these lineages will be critical for understanding both microbial evolution and regional patterns of gastric disease.
