The gut resistome as a potential determinant of immunotherapy response: antibiotics, immunometabolism, and precision...

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, yet their efficacy can be compromised by systemic antibiotic exposure and the resulting disruption of the gut microbiome. Across several tumor types, antibiotic use near the initiation of ICI therapy has frequently been associated with reduced progression-free and overall survival. Emerging data suggest that, beyond taxonomic shifts, antibiotic exposure is often accompanied by expansion of the gut resistome, the collective pool of antibiotic resistance genes. Antibiotic-associated dysbiosis and resistome enrichment are linked to alterations in short-chain fatty acid production, bile acid signaling, and microbial purine metabolism, pathways known to shape antigen presentation, T-cell differentiation, and immune tone. Accordingly, gut resistome profiling should be considered an emerging candidate biomarker. Potential strategies to restore a favorable gut ecosystem include dietary modulation, microbiome-based therapies such as probiotics or fecal microbiota transplantation, and emerging anti-resistance approaches designed to limit resistome expansion. Together, these findings support a resistome-centered framework for patient stratification and microbiome-targeted interventions in precision immune-oncology.