Human lifestyle-associated factors modulate the gut resistome

Antimicrobial resistance poses a serious threat to global public health in the 21st century. The human gut is a major reservoir of antimicrobial resistance genes and is strongly shaped by lifestyle factors linked to urbanization. Antibiotic use is widely known as a main driver of gut antimicrobial resistance; however, lifestyle encompasses other host and environmental determinants that also profoundly impact the gut resistome. These factors restructure gut microbiome composition and diversity, which, in turn, shape the abundance, persistence, and mobility of ARGs within the gut ecosystem. Lifestyle transitions along the urbanization gradient illustrate how antibiotic use, subsistence strategies, diet, agriculturally linked environmental exposures, host health, and global patterns of ARG distribution influence gut microbial diversity and ARG prevalence. Frequent antibiotic use in urban settings disrupts gut homeostasis and promotes resistome expansion. Transitions from traditional subsistence strategies to industrialized food systems are associated with dietary changes, such as reduced fiber intake, contributing to lower gut microbial diversity and increased ARG burden. Agrarian practices involving close human and livestock contact and antimicrobial use in animal husbandry facilitate ARG dissemination through the food chain. Host physiological factors and environmental exposures across diverse geographic regions additionally influence gut microbiome resilience and resistome composition. Integrating microbial community structure with ARG profiles provides insight into how lifestyle factors shape the gut resistome and influence ARG emergence and spread.