Abstract

Antibiotics have transformed the management of infectious diseases but often have unintended adverse effects on the commensal intestinal microbiota. Loss of diversity in the gut microbiota, the disruption that is most evident after antibiotic exposure, has been identified as a key driver of metabolic homeostasis, immune regulation, and disease susceptibility. This review aims to study current evidence for indirect and long-lasting effects of antibiotics on the gut microbiome and to highlight clinical consequences. Specifically, this review focuses on four interrelated aspects of antibiotic-induced gut ecosystem disturbances: i) reduction in gut microbial diversity and diversity with reduced systemic ecological resilience accompanied by species richness depletion associated with accumulation of noncontributing operational taxonomic units to activities relevant to the host, corresponding to incompleteness in microbiome recovery; ii) loss or gain in metabolic activity for microbial metabolites such as short-chain fatty acids and enteric bile acids along with impairment of microbial vitamin synthesis; iii) polarization of mucosal and systemic immune responses regulating inflammation through microbiome-mediated mechanisms directed toward changes in T cell differentiation; and finally, iv) dysbiosis that increases susceptibility to recurrent infections by opportunistic microbes showing emerging resistance against antibiotics. Emerging evidence indicates that such perturbations driven by the antibiotics themselves can outlive treatment, especially after broad-spectrum antibiotic administration, and threaten intestinal barrier integrity and immune homeostasis. These results demonstrate that antibiotics-induced dysbiosis is a system-wide disruption involving tightly coupled microbial, metabolic, and immune pathways. This review also emphasizes the need for antimicrobial stewardship and strengthens the implementation of microbiome-targeted strategies to mitigate long-term adverse health events and improve infection resilience.

Key words: AMR, Dysbiosis, Gut microbiome, Immune modulation, Metabolic homeostasis, Therapy