NOD2 Does Not Influence Bacterial Community Structure in the Salmonella ΔaroA Chronic Inflammation Model

Mutations in the gene encoding the intracellular bacterial sensor, NOD2, are linked to risk of Crohn’s disease. We explored the role of NOD2 in shaping the intestinal microbiota during chronic inflammation induced through infection with Salmonella Typhimurium ΔaroA. We applied a robust experimental design to control for microbial variation by using littermates and a separately housed NOD1 strain for comparison. We found that NOD2 contributes to reducing the pro-inflammatory profile of the cecal environment, but plays no role in decreasing the severity of chronic inflammatory pathology 7 weeks p.i. Shifts in bacterial abundance throughout the acute response to infection, and during chronic inflammation, reflect inflammatory conditions shaped by many aspects of the immune response, independent of NOD2 functions. Curiously, NOD2-strain littermates (all genotypes) consistently showed more intense host and microbial responses to infection compared to the NOD1 strain, including secondary outgrowth of Salmonella that was still evident after 7 weeks. This observation suggests that differences in the microbiota prior to infection may contribute to determining the severity of the inflammatory response or the ability of the pathogen to persist in the host. Thus, when microbial variation is strictly controlled, NOD2 has negligible impact on chronic pathology or microbial abundance in this model.