ABSTRACT
Background 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.
Aims Examine impact of WSD on infection and colitis in response to gut bacterial pathogens.
Methods 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.
Results 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.
Altering microbiota via diet can profoundly impact the course and consequence of infection following exposure to gut bacterial pathogens.
Synopsis Dietary fiber results in a nutrient rich colon that is exploited by gut pathogens including C. rodentium and C. difficile, that rapidly colonize the colon. Hight-fat, low-fiber western-style diet results in a low-density gut microbiota unable to mediate clearance of pathogens from the colon. Inability to clear pathogens from the gut lumen promotes chronic low-grade inflammation and insulin resistance.
Graphic summary The low-fiber content of WSD impedes initial colonization of pathogens. Immune system functions appropriately irrespective of diet to clear pathogens from the mucosa. Commensal microbiota of mice fed GBC but not WSD is sufficient to eliminate pathogen from the lumen of the intestine. Underlying mechanisms discussed in text.