The stomach bacterium Helicobacter pylori is one of the most prevalent human pathogens. It has dispersed globally with its human host, resulting in a distinct phylogeographic pattern that can be used to reconstruct both recent and ancient human migrations. The H. pylori strains found in most Europeans today (hpEurope) have putatively originated from recombination of the two ancestral populations Ancestral Europe 1 and 2 (AE1 and AE2). However, there exist different hypotheses about when and where the hybridization took place, reflecting the complex demographic history of Europeans.
In a recent study, we screened biopsy samples from the gastrointestinal tract of the Iceman, a 5300-year-old European Copper Age mummy, for the presence of Helicobacter pylori. By using clinical metagenomic diagnostics and targeted genome capture, we determined the presence of H. pylori and reconstructed its complete genome. Comparison with contemporary H. pylori sequences and proteomics analysis classified the ancient H. pylori as a cytotoxic type strain that triggered already calprotectin release as a result of host inflammatory immune responses. Comparative analysis of ancient housekeeping gene fragments with a global multilocus sequence typing (MLST) database and comparative whole-genome analyses assigned the 5,300-year-old bacterium to the population hpAsia2 today commonly found in Central and South Asia. The “Iceman” H. pylori is a nearly pure representative of the bacterial population of Asian origin (AE1) that existed in Europe before hybridization, suggesting that the African population (AE2) arrived in Europe within the past few thousand years, which is much more recent than previously hypothesized.
Clinical metagenomics analysis of dated ancient specimens, ranging from microorganisms to multicellular species, opens a window into the past that enables scientists to address unique evolutionary research questions. Reconstructed ancient pathogen genomes display unique milestones in the understanding of the evolutionary history of infectious diseases.