Age- and diet-driven assembly of the gut antibiotic resistome in humans and food-producing animals

Antimicrobial resistance (AMR) poses a growing threat to global health, and increasing evidence reveals a substantial overlap in resistance genes between the gut microbiota of humans and food-producing animals, suggesting potential for cross-species transmission. Understanding the early-life development of the gut resistome is essential for designing effective AMR prevention strategies. This review synthesizes current knowledge on the age-dependent assembly of the gut resistome in both humans and food-producing animals, highlighting a consistent pattern of high antimicrobial resistance genes (ARGs) loads at birth followed by a gradual decline with age. We emphasize the critical role of diet in shaping resistome dynamics, formula feeding and high-fat, high-protein diets are associated with increased ARGs burden, whereas breastfeeding and diverse, fiber-rich diets are linked to reduced ARG prevalence. Furthermore, we discuss the potential of probiotics and prebiotics to mitigate gut AMR, while underscoring the importance of assessing resistance gene transfer risk in functional food development. Finally, we outline key knowledge gaps and propose future research directions within the framework of "One Health". This review provides a comprehensive foundation for policy and intervention strategies to control gut-derived AMR and protect public health.