Plasmid-Mediated Antimicrobial Resistance in The HumanMicrobiome: A Scoping Review of Horizontal GeneTransfer During Antibiotic Exposure

Abstract

Background: AMR remains a critical global health threat, yet pathogen-focused surveillance ‎underestimates the commensal human microbiome as a resistance gene reservoir. Evidence linking ‎plasmid persistence, stress-associated mobilization, and clinical relevance remains fragmented.‎ Objective: This scoping review synthesized evidence on plasmid persistence mechanisms, ‎antibiotic- and stressor-associated horizontal gene transfer (HGT), and clinical or translational ‎implications of microbiome-associated AMR.‎ Methods: Following PRISMA-ScR guidelines, five databases (PubMed/MEDLINE, Embase, Web ‎of Science, Scopus, and Global Health) were searched for English-language studies published ‎between January 2010 and December 2025. From 1,200 records identified, 223 unique records ‎were screened after duplicate removal, and 35 met the inclusion criteria. Data were extracted on ‎plasmid maintenance, mobilization pathways, clinical relevance, and translational approaches.‎ Results: Sixteen studies on plasmid persistence showed that maintenance may be supported by ‎host–plasmid co-adaptation, compensatory evolution, regulatory remodeling, epistatic interactions, ‎and stability systems. Eight studies on stressor-associated mobilization indicated that HGT may be ‎influenced by SOS responses, metabolic disruption, redox imbalance, antibiotic-specific regulatory ‎effects, and selection-driven genetic exchange. Eleven clinical or translational studies highlighted ‎underdetection of plasmid-mediated AMR transmission and early evidence for microbiome-based ‎and anti-plasmid strategies, including fecal microbiota transplantation, CRISPR-based targeting, ‎conjugation inhibition, and RecA-targeted approaches.‎ Conclusion: Plasmid-mediated AMR in the human microbiome is shaped by persistence dynamics, ‎stress-associated mobilization, and clinical selective pressures. Plasmid-resolved surveillance, ‎standardized HGT detection, longitudinal studies, and validated microbiome-informed ‎interventions are needed to strengthen AMR mitigation‎.