Diet-driven cardiometabolic dysfunction as a potential amplifier of antimicrobial resistance: mechanistic evidence, gut resistome ecology, and dual-action nutraceutical interventions

Over the last 30 years, two population-scale health crises have emerged as the epidemic of diet-related cardiometabolic disease (obesity, type 2 diabetes, hypertension, and cardiovascular disease) and the spread of antimicrobial resistance (AMR) as a major cause of death globally. Typically, they are investigated and controlled independently of each other. AMR may be amplified by diet-induced cardiometabolic dysfunction, which is not a parallel but an upstream, under-recognized burden. We describe four convergent pathways that might contribute to the increased risk of resistance. Impaired host immunity leading to recurrent, difficult-to-treat infection and repeated antibiotic exposure; obesity-associated pharmacokinetic changes leading to subtherapeutic antibiotic concentrations in the system; diet-induced gut dysbiosis that increases the reservoir of antibiotic-resistance genes (the gut resistome); and a bidirectional loop in which cumulative antibiotic exposure itself seems to increase cardiovascular risk. We then placed functional foods, nutraceuticals, and specific bioactive compounds as dual-action levers that act on the metabolic driver and, for a subset of molecules, directly on bacterial fitness, virulence, or the resistome. The clearest single-molecule example is developed in the form of berberine, which provides metabolic correction through the AMPK pathway, while simultaneously providing FtsZ-targeting and efflux-modulating antibacterial activity. We propose a testable framework, the metabolic–AMR augmentation loop, and highlight the gaps in evidence for longitudinal and interventional studies. If this framework proves to be robust, then diet-induced metabolic dysfunction correction could become a viable AMR-mitigation strategy on its own and one not currently employed in existing stewardship programs.