Short-term alterations in dietary amino acids override host genetic susceptibility and reveal mechanisms of Salmonella Typhimurium small intestine colonization
Shealy, N.; Baltagulov, M.; de Brito, C.; McGovern, A.; Castro, P.; Schrimpe-Rutledge, A. C.; Malekshahi, C.; Condreanu, S. G.; Sherrod, S. D.; Jana, S.; Jones, K.; Machado Ribeiro, T. R.; McLean, J.; Beiting, D. P.; Byndloss, M. X.
Show abstract
In addition to individual genetics, environmental factors (e.g., dietary changes) may influence host susceptibility to gastrointestinal infection through unknown mechanisms. Herein, we developed a model in which CBA/J mice, a genetically resistant strain that tolerates intestinal colonization by the enteric pathogen Salmonella Typhimurium (S. Tm), rapidly succumb to infection after exposure to a diet rich in L-amino acids (AA). In mice, S. Tm-gastroenteritis is restricted to the large intestine (cecum), limiting their use to understand S. Tm small intestine (ileum) colonization, a feature of human Salmonellosis. Surprisingly, CBA mice fed AA diet developed ileitis with enhanced S. Tm ileal colonization. Using germ-free mice and ileal-fecal slurry transplant, we found diet-mediated S. Tm ileal expansion to be microbiota-dependent. Mechanistically, S. Tm relied on Fructosyl-asparagine utilization to expand in the ileum during infection. We demonstrate how AA diet overrides host genetics by altering the gut microbiotas ability to prevent S. Tm ileal colonization.
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