Although HIV-associated enteropathy is presumed to enhance disease progression and is a major cause of diarrhea and malnutrition in patients world-wide, the kinetics and molecular mechanisms of pathogenesis remain poorly understood. We hypothesize that disruption of homeostatic trialogue between host adaptive and innate immunity and the intestinal microbiota (dysbiosis) is an underlying cause of enteropathy in immunodeficiency virus infection. The proposed research will utilize a systems biology approach to test this hypothesis, characterizing the microbial signature of intestinal dysbiosis and the mechanisms of its role in enteropathy in the SIV infected rhesus macaque model. Findings from the study will provide unprecedented insights into the molecular and cellular basis of enteropathy in SIV and HIV infection.
We propose to identify the different types, or species, of bacteria that colonize the surface of the intestinal epithelium in rhesus macaques, and identify modulations in the bacterial species that are associated with pathogenesis and disease progression in simian immunodeficiency virus (SIV) infected animals. In addition, we will determine how changes in host gene expression in epithelial cells contribute to changes in bacteria populations.