Antibiotic-Driven Gut Microbiome Dysbiosis: Resistome Dynamics, Metabolic Disruption, and Paths to Restoration

The gut microbiome is a dynamic ecosystem that plays essential roles in host metabolism, immune regulation, colonization resistance, and maintenance of intestinal homeostasis. Antibiotic exposure profoundly disrupts this ecosystem by reducing microbial diversity, depleting beneficial commensals, reshaping microbial metabolic functions, and remodeling the gut resistome through the selection and dissemination of antibiotic resistance genes (ARGs). Increasing evidence from longitudinal metagenomic, multi-omics, and experimental studies indicates that these perturbations may persist long after antibiotic withdrawal due to incomplete ecological recovery, sustained mobile genetic element-mediated ARG dissemination, and altered microbiome resilience. Beyond antimicrobial resistance, antibiotic-induced dysbiosis has been associated with reduced short-chain fatty acid production, altered bile acid metabolism, impaired epithelial barrier function, and broader disturbances in host metabolic homeostasis, although many of these relationships remain associative rather than causal. This review provides an integrated overview of antibiotic-driven gut microbiome dysbiosis, emphasizing the ecological, functional, metabolic, and resistome-level consequences of antibiotic exposure together with the mechanisms governing microbiome recovery. Current microbiome-targeted restoration strategies, including probiotics, phage therapy, fecal microbiota transplantation, and next-generation microbiome therapeutics, are critically evaluated with particular attention to their evidence maturity, limitations, and translational potential. Finally, key knowledge gaps and future research priorities are discussed to support the development of more effective microbiome-preserving antimicrobial strategies and to limit the long-term dissemination of antimicrobial resistance.