Diet can override genetic susceptibility to intestinal pathogen through microbiota modulation. Microbiota effect

The gut microbiota participates to the colonization resistance against pathogens but the mechanisms involved remain poorly understood. Here we show that caspase recruitment domain family member 9 (CARD9), one of the numerous inflammatory bowel diseases susceptibility genes, is required for shaping the gut microbiota which promotes colonization resistance to the enteric pathogen Citrobacter rodentium, a model for human infections with attaching-and-effacing bacteria. Transfer of the microbiota from Card9–/– mice to wild-type, germ-free recipients increases their susceptibility to C. rodentium in the early phase of infection. The microbiota of Card9–/– mice fails to outcompete the monosaccharides-consuming C. rodentium. This phenotype can be overridden by a diet using polysaccharides as a sole hydrocarbon source. Thus, genetic defect affects the composition and the function of the gut microbiota, modulating susceptibility to intestinal pathogen. However diet intervention can override genetic susceptibility to intestinal pathogen by shaping the microbiota.