Date of Award

January 2016

Degree Type


Degree Name

Doctor of Philosophy (PhD)


Comparative Pathobiology

First Advisor

Chang Kim

Committee Member 1

Yava L Jones

Committee Member 2

Harm Hogenesch

Committee Member 3

John A Patterson


Intestinal microbiota regulate various biological processes in the host. Intestinal microbiota produce short chain fatty acids (SCFAs) via dietary fiber fermentation. SCFAs have profound effects on the immune system. We investigated the roles of SCFAs in regulating T cell differentiation and tissue inflammation. We found that SCFAs regulate T cell differentiation and T cell-mediated immunity. SCFAs enhanced both IL-10+ T cell and Th1/Th17 effector T cell differentiation. SCFAs inhibited histone deacetylase (HDAC) activity and upregulated acetylation of p70 S6 kinase and mTOR activation in T cells. We also found that prolonged exposure to high concentration of SCFA cause ureteral obstruction and hydronephrosis. SCFAs activated mTOR signaling in renal T cells and developed T cell-mediated inflammation in the ureter and kidneys. In sum, SCFAs promote immunity but can also regulate inflammatory diseases.