Helicobacter pylori In Free‐Living Amoebae: A Potential Environmental Reservoir for Persistence and Transmission

Helicobacter pylori (H. pylori) is a highly adapted gastric pathogen responsible for one of the most prevalent chronic bacterial infections worldwide and a major cause of gastritis, peptic-ulcer disease, and gastric cancer. Traditionally considered predominantly a human-associated microorganism transmitted via oral-faecal routes, growing evidence challenges this paradigm by demonstrating its persistence outside the human host through interactions with free-living amoebae (FLA). This review critically examines current knowledge of the biological and ecological interplay between H. pylori and FLA, focusing on amoeba-mediated internalisation, intracellular survival, morphological plasticity, and protection from environmental stressors. We highlight FLA's ability to support the persistence of spiral and viable but non-culturable (VBNC) coccoid forms of H. pylori, potentially enabling prolonged survival in aquatic and food-associated environments and raising concerns regarding potential waterborne and foodborne transmission. Given the limited direct experimental evidence, we integrate insights from amoeba-resistant bacteria to illustrate convergent intracellular persistence strategies. By considering FLA as a potential underrecognised environmental reservoir, this review expands current frameworks of H. pylori transmission and persistence, with potential relevance to settings with inadequate sanitation. We also outline key mechanistic and methodological gaps and call for standardised models to clarify the ecological significance of these interactions and inform surveillance and control strategies.