Meat without vegetables: An ancient ecotype of Helicobacter pylori found in Indigenous populations and animal adapted lineages

The colonization of our stomachs by Helicobacter pylori is believed to predate the oldest splits between extant human populations. We identify a “Hardy” ecotype of H. pylori isolated from people belonging to Indigenous populations in Siberia, Canada and USA. The ecotype shares the ancestry of “Ubiquitous” H. pylori from the same geographical region in most of the genome but has nearly fixed SNP differences in 100 genes, many of which encode outer membrane proteins and previously identified virulence factors. H. acinonychis, found in big cats, and a newly identified primate-associated lineage both belong to the Hardy ecotype and both represent human to animal host jumps. Most strains from the ecotype encode an additional iron-dependent urease that is shared by Helicobacter from carnivorous hosts, as well as a tandem duplication of vacA, encoding the vacuolating toxin. We conclude that H. pylori split into two highly distinct ecotypes approximately 300,000 years ago and that both dispersed around the globe with humans. Coexistence has likely been possible because the ecotypes are adapted to different host diets, but the Hardy ecotype has gone extinct in most parts of the world. Our analysis also pushes back the likely length of the association between H. pylori and humans.