Colonization resistance: the role of gut microbiota in preventing Salmonella invasion and infection Original paper

What was reviewed?

This paper reviewed the concept of colonization resistance and the central role of the gut microbiota in preventing Salmonella invasion and infection. The authors synthesized mechanistic, experimental, and translational evidence to explain how resident gut microbes create a hostile environment that limits pathogen establishment, expansion, and virulence. The review framed colonization resistance as an integrated ecological and immunological process rather than a single defensive mechanism. It detailed how microbial competition for nutrients, production of antimicrobial compounds, generation of bioactive metabolites, and modulation of host immune pathways collectively restrict Salmonella colonization. In parallel, the paper critically examined how Salmonella exploits inflammation, altered metabolism, and microbiota disruption to overcome these barriers, positioning infection as the outcome of a dynamic host–microbiota–pathogen interaction rather than simple exposure to a pathogen.

Who was reviewed?

The review drew on studies involving human populations, livestock, and experimental animal models, particularly mice and gnotobiotic systems designed to isolate specific microbial functions. Human data included epidemiological and clinical observations of Salmonella infection risk following antibiotic use, dietary changes, and immune compromise. Animal models provided mechanistic insights into defined microbial consortia, germ-free conditions, and targeted colonization experiments that clarified causal relationships between specific microbes, metabolites, and immune responses. By integrating evidence across hosts and experimental systems, the review captured conserved principles of colonization resistance while acknowledging interspecies and interindividual variability.

What were the most important findings?

The review demonstrated that effective resistance to Salmonella depends on a multilayered microbiome-driven defense. Commensal bacteria restrict Salmonella growth through nutrient competition, particularly for carbon sources, iron, zinc, and respiratory electron acceptors, thereby limiting pathogen metabolic flexibility. Major microbial associations included Bacteroides species that degrade complex polysaccharides and generate short-chain fatty acids, Escherichia coli strains such as E. coli Nissle 1917 that sequester iron via siderophores, and defined microbial communities capable of depleting oxygen and nitrate required for Salmonella respiration. Microbial metabolites such as acetate, propionate, and butyrate directly suppressed Salmonella growth and downregulated virulence gene expression, while secondary bile acids and tryptophan-derived indoles interfered with invasion pathways. Indirect mechanisms were equally critical, with the microbiota reinforcing mucus layer integrity, stimulating antimicrobial peptides such as REG3γ, and driving IgA-mediated containment. The review also highlighted that Salmonella can subvert these defenses by inducing inflammation, exploiting host-derived metabolites, and using specialized secretion systems to outcompete commensals.

What are the greatest implications of this review?

The major clinical implication is that preventing Salmonella infection requires preserving microbiome structure and function rather than relying solely on pathogen-directed therapies. The findings support microbiota-targeted strategies, including diet-based interventions, rational probiotic or consortium design, and cautious antibiotic use, as viable approaches to strengthen colonization resistance. For clinicians, the review underscores that susceptibility to enteric infection reflects ecosystem disruption, not merely pathogen exposure.