Gut Microbiome and Intestinal Colonization by Carbapenem-Resistant Enterobacterales: Mechanisms, Clinical Implications, and Microbiome-Based Interventions

The intestinal microbiome plays a pivotal role in colonization resistance against antimicrobial-resistant pathogens, and disruption of this ecosystem can facilitate intestinal carriage of carbapenem-resistant Enterobacterales (CRE), subsequent invasive infection, and transmission. This review examines the ecological and clinical determinants of CRE colonization, persistence, and progression to infection, emphasizing interactions among the gut microbiota, host factors, antimicrobial exposure, and pathogen characteristics. We further evaluate emerging strategies for restoring or enhancing colonization resistance, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), engineered microbial systems, CRISPR–Cas technologies, and bacteriophages. These approaches offer potential avenues for investigating microbiome restoration and pathogen-targeted interventions. However, the strength of evidence varies substantially across strategies, and current evidence does not support their routine use for CRE decolonization. Further well-designed clinical studies are needed to establish the efficacy, safety, and durability of these interventions and to identify precision-based approaches that effectively control CRE while preserving microbiome integrity.