Western-style diet impedes colonization and clearance of Citrobacter rodentium

Western-style diet (WSD), which is high in fat and low in fiber, lacks nutrients to support gut microbiota. Consequently, WSD reduces microbiota density and promotes microbiota encroachment, potentially influencing colonization resistance, immune system readiness, and thus host defense against pathogenic bacteria. Here we examined the impact of WSD on infection and colitis in response to Citrobacter rodentium. We observed that, relative to mice consuming standard rodent grain-based chow (GBC), feeding WSD starkly altered the dynamics of Citrobacter infection, reducing initial colonization and inflammation but frequently resulting in persistent infection that associated with low-grade inflammation and insulin resistance. WSD's reduction in initial Citrobacter virulence appeared to reflect that colons of GBC-fed mice contain microbiota metabolites, including short-chain fatty acids, especially acetate, that drive Citrobacter growth and virulence. Citrobacter persistence in WSD-fed mice reflected inability of resident microbiota to out-compete it from the gut lumen, likely reflecting the profound impacts of WSD on microbiota composition. These studies demonstrate potential of altering microbiota and their metabolites by diet to impact the course and consequence of infection following exposure to a gut pathogen. Author summary Broad changes in societal dietary habits, especially consumption of processed foods that are frequently rich in fats and simple carbohydrates but lacking in fiber are widely believed to have contributed mightily to the increased incidence of chronic inflammatory diseases that has accompanied industrialization. Here we showed that dietary fiber results in a favorable colon environment that promotes C. rodentium growth and virulence. Consequently, a high-fat, low-fiber western-style diet reduced initial C. rodentium colonization but also resulted in a gut microbiota that was unable to mediate C. rodentium clearance from the colon. Persistent C. rodentium colonization associated with chronic low-grade inflammation and insulin resistance. Our study suggests that such pathogens, or perhaps even pathobionts like organisms such as E. coli, may not be readily cleared from hosts consuming high-fat low-fiber diets and thereby promote the chronic, often low-grade, inflammation related diseases.