The role of the gut microbiome in antibiotic-driven antimicrobial resistance.

Antimicrobial resistance (AMR) is one of the most pressing threats to global health system. The human gut harbors a complex microbial ecosystem coordinated through mechanisms of metabolic interdependence. The gut microbiota plays a vital role in normal growth and physiological processes of the human body. It serves both as a target of antibiotic-mediated disruption and as a reservoir for the propagation of antimicrobial resistance genes. Although antibiotics remain indispensable for the treatment of bacterial infections, their broad ecological impact on the gut microbiota can undermine the microbial balance that protects the host against pathogen invasion and metabolic dysfunction. The gut microbiome also functions as a reservoir of antimicrobial resistance genes collectively termed the "resistome," which can be mobilised and transferred between commensal and pathogenic bacteria via horizontal gene transfer mechanisms such as conjugation, transformation, and transduction. This review examines the composition and functions of the human gut microbiota, the mechanism of antibiotic-induced gut dysbiosis, and the role of host factors like age, genetics, diet and immune status, on microbiome dynamics and AMR development. We further evaluate emerging methods for resistome characterisation, which include PCR, next-generation sequencing, functional metagenomics and artificial intelligence-driven tools. Finally, we discuss microbiome-targeted therapeutic strategies such as faecal microbiota transplantation (FMT), phage therapy, CRISPR-based therapies, and antimicrobial peptides for combating AMR and restoring gut microbial homeostasis. Overall, this review highlights that maintaining and re-establishing the integrity of the gut microbiome should be considered a fundamental component of antimicrobial stewardship strategies aimed at controlling AMR worldwide.