Human gut microbiome has risen as a critical nexus in the global landscape of antimicrobial resistance (AMR), acting both as a reservoir and a driver of multidrug‐resistant organisms (MDROs). This review explores the mechanistic foundations by which the gut microbiota contributes to resistance development, focusing on the acquisition and spread of antibiotic resistance genes (ARGs) through horizontal gene transfer, mobile genetic elements, and other ecological imbalances triggered by antibiotic exposure. Strong emphasis is implied on the clinical implications of gut‐mediated resistance in certain high‐exposure settings such as critical care units and immunocompromised patients. We critically evaluate current and emerging therapeutic strategies including fecal microbiota transplantation (FMT), genetically engineered probiotics, phage therapy, enzybiotics, and photodynamic approaches that focus on restoring microbial balance and reducing ARG burden. A novel, three‐tiered microbiome‐aware antimicrobial stewardship model is proposed to guide integration of these strategies into clinical practice. The review concludes with future perspectives on research priorities, including the need for precision resistome surveillance, ethical regulatory frameworks, and microbiome‐informed antibiotic policies. By reframing the gut microbiome from a passive site of colonization to an actionable therapeutic target, this review underscores its centrality in the ongoing battle against AMR.
Shashikanth et al. (Thu,) studied this question.