Rebuilding the gut ecosystem: Emerging strategies targeting the microbiota in antibiotic-associated diarrhea

Antibiotic-associated diarrhea (AAD) is a prevalent iatrogenic complication of antibiotic therapy, primarily triggered by dysbiosis and loss of intestinal homeostasis. The traditional interventions, such as empirical probiotic use, have shown a modest and a heterogeneous efficacy. This review integrates the current mechanistic understanding of AAD through the lens of the microbiota–mucosal–immune axis and provides a comprehensive overview of emerging therapeutic strategies. By integrating evidence from metagenomics, metabolomics, and immunology, we highlight next-generation approaches, including rationally engineered probiotics, standardized fecal microbiota transplantation (FMT), and synthetic-biology-derived interventions. Recent progress in multi-omics technologies and machine learning has enabled patient-stratified modulation of the gut microbiota, moving beyond empirical supplementation toward precision ecological reprogramming. These advanced therapies demonstrate superior outcomes in restoring microbial diversity, strengthening epithelial barrier function, and re-establishing immunological homeostasis. Ultimately, the management of AAD requires a systems-biology strategy that leverages real-time microbiome analytics for targeted, accurate, and sustainable restoration of gut health.