Climate and One Health exposure gradients decouple antimicrobial resistance burden from resistome composition in the gut microbiome of healthy young adults from across the world
Antimicrobial resistance is a major global health threat, yet international comparisons of the human gut resistome remain limited, and the relative contributions of climatic, environmental, socioeconomic, and dietary drivers to resistome burden and composition are poorly resolved. We characterised the gut resistome across 34 countries spanning four continents using shotgun metagenomic sequencing of pooled stool samples from 116 young adult medical students newly enrolled at the University of Debrecen, Hungary. This deliberately homogeneous sampling frame minimised within-country socioeconomic heterogeneity and allowed country-level differences to be more confidently attributed to country-of-origin exposures. Country-level environmental (temperature, PM2.5, precipitation), socioeconomic (Human Development Index), and dietary data (national dietary archetypes, Alternative Healthy Eating Index) were integrated with resistome profiles, alongside veterinary antibiotic use estimates (mg/PCU). Total resistance gene burden was primarily driven by climatic factors: temperature explained 15 percent of variance, corresponding to a 22 percent increase in total ARG abundance per 10 C, and this effect was independent of continent (Type II p = 0.030). In contrast, resistome composition was structured by continent, dietary pattern, and veterinary antibiotic use. Sub-Saharan African countries with low-diversity subsistence diets diverged significantly from the remaining cohort (PERMANOVA R2 = 0.121, p = 0.003), with tetracycline resistance enriched (log2FC = +0.50) and macrolide, and nitrofuran resistance depleted. Gut resistome burden and composition are shaped by distinct drivers, with region-specific resistance signatures reflecting divergent agricultural, clinical, and environmental exposures, findings that inform region-tailored antimicrobial stewardship strategies.