The gut microbiota plays a critical role in maintaining host health by controlling pathogens and pathobionts. It enhances intestinal barrier function, supports immune system development, and aids in nutrient acquisition. The microbiota prevents pathogen colonization through competitive metabolic interactions, localization to intestinal niches, and induction of host immune responses. Pathogens have evolved strategies to evade these defenses, leading to infections and diseases. The composition and distribution of the microbiota are influenced by nutrient availability and ecological interactions among bacteria. The small intestine is rich in nutrients that support the growth of certain bacteria, while the large intestine harbors bacteria that can utilize host-derived polysaccharides. Disruption of the microbiota can lead to the overgrowth of harmful bacteria, such as Clostridium difficile and vancomycin-resistant Enterococcus. The microbiota also promotes host immunity by enhancing barrier function, producing antimicrobial peptides, and regulating inflammatory responses. Pathogens can overcome colonization resistance by utilizing specific nutrients, localizing to distinct niches, or inducing host inflammation that favors their growth. Understanding these interactions may lead to new therapeutic approaches for infectious diseases. Microbiota-targeted therapies, such as fecal microbiota transplantation, show promise in treating infections like Clostridium difficile. However, the mechanisms by which the microbiota regulates pathogen resistance remain poorly understood, and further research is needed to develop effective treatments.The gut microbiota plays a critical role in maintaining host health by controlling pathogens and pathobionts. It enhances intestinal barrier function, supports immune system development, and aids in nutrient acquisition. The microbiota prevents pathogen colonization through competitive metabolic interactions, localization to intestinal niches, and induction of host immune responses. Pathogens have evolved strategies to evade these defenses, leading to infections and diseases. The composition and distribution of the microbiota are influenced by nutrient availability and ecological interactions among bacteria. The small intestine is rich in nutrients that support the growth of certain bacteria, while the large intestine harbors bacteria that can utilize host-derived polysaccharides. Disruption of the microbiota can lead to the overgrowth of harmful bacteria, such as Clostridium difficile and vancomycin-resistant Enterococcus. The microbiota also promotes host immunity by enhancing barrier function, producing antimicrobial peptides, and regulating inflammatory responses. Pathogens can overcome colonization resistance by utilizing specific nutrients, localizing to distinct niches, or inducing host inflammation that favors their growth. Understanding these interactions may lead to new therapeutic approaches for infectious diseases. Microbiota-targeted therapies, such as fecal microbiota transplantation, show promise in treating infections like Clostridium difficile. However, the mechanisms by which the microbiota regulates pathogen resistance remain poorly understood, and further research is needed to develop effective treatments.