Heteroresistance in Helicobacter pylori: From Within-Host Population Heterogeneity to Detection and Clinical Implications

Heteroresistance (HR) in Helicobacter pylori (H. pylori) refers to the coexistence of subpopulations with differing susceptibilities to the same antimicrobial. Understanding HR requires considering within-host population heterogeneity and evolutionary dynamics beyond reported detection rates. HR has been reported at host, intragastric spatial, individual-colony, and resistance-associated genetic levels, which provide interrelated but non-equivalent evidence. Mutations, recombination, and phenotypic variation may contribute to subpopulation differences, whereas spatial structure, antimicrobial selection, and relative fitness may influence their coexistence and persistence. However, direct longitudinal evidence of HR evolution remains limited. Reported HR prevalence varies with sampling methods, colony selection, analytical sensitivity, and operational criteria. Evidence linking HR to eradication outcomes remains insufficient to establish its independent clinical significance. HR interpretation should therefore account for within-host population structure, evolutionary dynamics, detection methods, and operational definitions. Longitudinal, multicenter studies are needed to clarify its clinical relevance and implications for antimicrobial susceptibility testing.