Gut Microbiota and Colonization Resistance against Bacterial Enteric Infection Original paper

What was reviewed?

This paper reviewed how the gut microbiota mediates colonization resistance against bacterial enteric infections, focusing on ecological, metabolic, and microbiological mechanisms that prevent pathogen establishment and disease. The authors synthesized mechanistic and translational evidence to explain how a healthy gut microbial ecosystem restricts invasion by enteric pathogens through antimicrobial production, metabolic competition, maintenance of epithelial barriers, and interaction with bacteriophages. Rather than treating enteric infection as a simple host–pathogen interaction, the review positioned infection as a failure of microbiome-driven ecosystem stability. It emphasized that colonization resistance is an emergent property of complex microbial networks whose disruption—most commonly by antibiotics or other medications—creates permissive conditions for pathogens such as Clostridioides difficile, Salmonella enterica, enterohemorrhagic Escherichia coli, Shigella flexneri, Campylobacter jejuni, Vibrio cholerae, and Yersinia enterocolitica to colonize and cause disease.

Who was reviewed?

The review integrated data from human clinical populations, including hospitalized patients, antibiotic-exposed individuals, and populations at risk for enteric infection, alongside extensive evidence from animal models and in vitro systems. Germ-free mice, antibiotic-treated mice, gnotobiotic models, and controlled colonization experiments were central to establishing causal relationships between specific microbial functions and pathogen resistance. Human data were drawn from observational studies, fecal microbiota transplantation outcomes, and clinical associations linking microbiome disruption to infection susceptibility. This combination allowed the authors to align mechanistic insights with clinically relevant outcomes.

What were the most important findings?

The review demonstrated that colonization resistance is mediated through multiple coordinated mechanisms driven by commensal microbes. Short-chain fatty acid–producing bacteria emerged as major microbial associations, with acetate, propionate, and butyrate shaping luminal pH, suppressing pathogen growth, and modulating virulence gene expression. Secondary bile acid–producing Clostridia, including species such as Clostridium scindens, played a critical role by converting primary bile acids that promote pathogen germination into secondary bile acids that inhibit vegetative growth, particularly for C. difficile.

Bacteriocin-producing commensals, including Lactobacillus, Enterococcus, and Escherichia coli strains, directly inhibited pathogens such as Listeria monocytogenes, Salmonella Typhimurium, and Yersinia enterocolitica without broadly disrupting the microbiome. Nutrient competition was shown to be highly pathogen-specific, with commensals depriving pathogens of key carbon sources, amino acids, and micronutrients such as iron and zinc. The integrity of the mucus layer also emerged as a central defense, with microbiota-accessible carbohydrate depletion leading to mucus erosion and increased pathogen proximity to the epithelium. The review further highlighted bacteriophages as underappreciated contributors to colonization resistance by selectively targeting pathogens and shaping microbial community structure.

What are the greatest implications of this review?

The major clinical implication is that susceptibility to bacterial enteric infection reflects disruption of microbiome function rather than mere pathogen exposure. The findings strongly support microbiome-preserving strategies, including antibiotic stewardship, diet-based interventions, rational probiotic or consortium therapies, and targeted microbiota restoration. For clinicians, the review reinforces that restoring ecosystem function is central to preventing infection recurrence and reducing disease severity.