The Enteric Microbiome/Virome in HIV-Associated Neurocognitive Decline
HIV can infect the nervous system and is associated with neurological symptoms including cognitive decline and motor dysfunction. These neurological effects remain common despite antiretroviral therapy; inflammation is thought to play a major role in its etiology. Increasing evidence suggests that enteric microbial composition can profoundly influence many neurological conditions including anxiety, depression, cognition, autism and stroke. This microbiota-gut-brain axis is a bi-directional communication system between the central nervous system and gut microbiota and plays a role in maintaining neuroendocrine and neuroimmune homeostasis. Intestinal bacteria produce metabolites including short chain fatty acids and neurotransmitters that can enter the central nervous system, directly affecting neuronal activity, or interact with the immune system thus indirectly affecting brain function. We have previously shown that immunodeficiency from HIV infection is associated with alterations in enteric bacterial diversity and expansion of potentially pathogenic enteric bacteria and viruses. These alterations in the enteric microbiome may play a role in chronic immune activation in people living with HIV. In collaboration with Dr. Giovanni Schifitto, we are assessing the influence of the microbiome, virome and microbial translocation from the gut on neurocognitive decline in subjects with HIV, both before and after short-term antiretroviral therapy to identify key viral or bacterial targets for future therapeutics.