Dietary modulation of the gut resistome: ecological and metabolic pathways driving antimicrobial resistance

Antimicrobial resistance (AMR) is traditionally viewed as a consequence of antibiotic exposure and genetic adaptation; however, resistance also emerges from the ecological and metabolic context of microbial communities. The human gut microbiome represents a major reservoir of antibiotic resistance genes (ARGs), and diet is increasingly recognised as a dominant regulator of its structure and function. Here, I synthesise current evidence and propose a conceptual framework in which diet shapes resistome dynamics through three interrelated pathways: ecological selection, metabolic regulation, and physicochemical modulation of horizontal gene transfer. Dietary components influence microbial composition, metabolic activity, and the spatial organisation of fermentation along the colon. Diverse fibre types differentially regulate short-chain fatty acid production and microbial competition, whereas high-fat, low-diversity diets destabilise communities and favour opportunistic taxa. Beyond macronutrients, food additives and the physical structure of food alter gut barrier function, microbial stress responses, and spatial ecology, thereby influencing resistome stability. Diet-induced metabolic states further determine antibiotic susceptibility, including transitions between tolerance and resistance. Taken together, this integrated ecological perspective positions diet as a modifiable driver of AMR and highlights nutritional strategies as complementary approaches to mitigating resistome expansion.