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The human gastrointestinal tract is colonized by a complex microbial ecosystem, the gut microbiota, which is pivotal in maintaining host health and mediating resistance to diseases. This review delineates colonization resistance (CR), a critical defensive mechanism employed by the gut microbiota to safeguard against pathogenic bacterial invasions, notably by . We detail the mechanisms through which the gut microbiota impedes colonization, including nutrient competition, production of antimicrobial peptides, synthesis of microbial-derived metabolites, and modulation of the host immune response. Additionally, we examine how dietary interventions can influence these mechanisms, thereby augmenting the protective role of the gut microbiota. The review also discusses the sophisticated strategies utilized by to overcome these microbial defenses. A thorough understanding of these complex interactions between microbial symbionts and pathogens is crucial for the development of innovative therapeutic strategies that enhance CR, aiming to prevent or treat microbial infections effectively.