Role for the microbiota in development of herpes stromal keratitis

A curious, unexplained anomaly is that many people shed reactivated HSV1 in the cornea yet fail to develop HSK, and even more remarkable are the patients who experience recurrent epithelial lesions yet never develop HSK. We posit that gut microbiota-derived changes in host immunity are the primary drivers of these anomalies, because oral antibiotic depletion of the gut microbiota prior to ocular HSV1 infection significantly reduced angiogenesis and HSK. The hypothesis of this proposed project is: gut microbiota affect the susceptibility to and severity of HSK through immune-mediated processes. The specific aims to test our novel hypothesis.Specific Aim 1. Identify gut bacteria, gut bacterial genes/gene products/pathways, and host immune processes that correlate with varying susceptibilities to and severity of HSK and HSE following HSV1 infection.Specific Aim 2. Causally test bacteria for their abilities to alter the susceptibilities to and severity of HSK and HSE following HSV1 infection, and identify the associated changes in host immunity.