Western-style diet impedes colonization and clearance of gut bacterial pathogens

Abstract

Western-style diet (WSD), which is high in fat and low in fiber, lacks nutrients to support gut microbiota. Consequently, WSD promotes microbiota encroachment and reduces microbiota density, potentially influencing colonization resistance, immune system readiness, and, consequently host defense against pathogenic bacteria. Additionally, the low-nutrient colonic environment resulting from WSD might impact bacterial pathogens. Hence, we examined the impact of WSD on infection and colitis in response to gut bacterial pathogens. Mice fed grain-based chow (GBC), WSD, or various versions thereof, were orally infected with Citrobacter rodentium or C. difficile. Colonization and its consequences, including inflammation and death were monitored. We observed that WSD delayed Citrobacter growth, reduced its virulence gene expression and ameliorated inflammation. However, while GBC-fed mice uniformly cleared Citrobacter and were impervious to subsequent Citrobacter challenges, most WSD-fed mice remained chronically infected with Citrobacter while those that cleared it were highly prone to re-infection. Such persistent proneness to Citrobacter infection did not reflect reduced immune responsiveness but rather reflected reduced colonization resistance likely from the low microbiota density resulting from WSD feeding. While persistent Citrobacter infection did not cause overt inflammation, it was associated with low-grade inflammation in colon and adipose tissue that was associated with insulin resistance. An analogous pattern was seen in response to C. difficile with WSD resulting in delayed colonization and mortality while enriching WSD with fiber hastened colonization but afforded clearance and survival. Thus, altering microbiota via diet can profoundly impact the course and consequence of infection following exposure to gut bacterial pathogens.