Immune control of the gut resistome, antibiotic resistance genes in the microbiome: mechanisms of their regulation during colonization and infection

Antimicrobial resistance (AMR) is a major global health threat and a daily clinical challenge in infectious diseases, particularly among hospitalized, immunocompromised, and critically ill patients. Multidrug-resistant organisms (MDROs) frequently emerge from the intestinal microbiota, where the gut resistome—the aggregate of antibiotic resistance genes within commensal and pathogenic bacteria—serves as a dynamic reservoir for subsequent invasive infection and transmission. While antibiotic exposure remains a key driver of resistance selection, growing evidence suggests that host immune status critically shapes resistome composition, stability, and dissemination.Under physiological conditions, innate and adaptive immune mechanisms—including antimicrobial peptides, secretory IgA, epithelial barrier integrity, inflammasome activation, and cytokine-mediated metabolic regulation—maintain colonization resistance and constrain pathobiont expansion. However, immune dysregulation resulting from inflammation, malignancy, transplantation, biologic therapies, chemotherapy, or critical illness may disrupt these ecological controls. Such perturbations can create permissive niches that promote MDRO colonization, resistance gene amplification, and horizontal gene transfer. Yet, the immune determinants that define whether the gut ecosystem remains resilient or progresses toward dominance by resistant pathogens remain insufficiently characterized.This Research Topic aims to advance mechanistic and translational understanding of how immune–microbiota interactions regulate the gut resistome and influence clinical AMR risk. We hypothesize that immune context—rather than antibiotic exposure alone—is a central determinant of MDRO emergence, persistence, and invasion. By integrating mucosal immunology, microbial ecology, and infectious diseases research, this collection seeks to define immune pathways and biomarkers that predict resistome expansion and progression from colonization to infection. A deeper understanding of these mechanisms may inform precision strategies combining antimicrobial stewardship, microbiota restoration, and immune modulation to prevent MDRO-related disease.The scope of this Research Topic includes mechanistic and clinically relevant studies linking immune function to gut resistome dynamics and MDRO outcomes. Emphasis is placed on translational studies providing insights with direct implications for infectious diseases practice.We welcome contributions addressing, but not limited to:• Immune regulation of colonization resistance and MDRO persistence• Inflammation-driven horizontal gene transfer and resistance gene mobilization in clinical settings• Effects of immunosuppression, transplantation, chemotherapy, biologics, and critical illness on MDRO colonization and infection risk• Longitudinal studies linking immune signatures to MDRO acquisition, bloodstream infection, or transmission• Multi-omics and computational approaches predicting resistome shifts in high-risk patient populations• Biomarkers for identifying patients at risk for MDRO infection• Microbiota-based, immunomodulatory, or combined strategies to reduce MDRO reservoirs and prevent invasive diseaseWe welcome Original Research, Review, Mini Review, Perspective, Brief Research Report, and Methods articles that provide mechanistic, translational, or interdisciplinary insights into immune control of the gut resistome in the context of infectious diseases. Studies bridging bench-to-bedside investigation and clinically meaningful outcomes are particularly encouraged. Topic editors: Larisa Miftode, Mariana PAVEL-TANASA, Coralia Bleotu Source: https://www.frontiersin.org/research-topics/78882/immune-control-of-the-gut-resistome-antibiotic-resistance-genes-in-the-microbiome-mechanisms-of-their-regulation-during-colonization-and-infection