Microbiome Core

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PROJECT SUMMARY/ABSTRACT: MICROBIOME CORE The Microbiome (MIBI) Core plays an essential role in the HNRC by enabling researchers to investigate the emerging, complex links between the gut microbiome, HIV, associated comorbidities, and biological mechanisms involved in neurocognitive impairment (NCI), mood disorders, and more complex neurobehavioral phenotypes that include both. In recent years, the gut microbiome has been strongly associated with neurologic and mood disorders in individual studies, although few studies have considered them together, and none in the context of HIV. In particular, questions about how HIV infection and ART may impact gut barrier dysfunction and central nervous system sequelae from a microbiome perspective have not been well studied. However, detailed mechanistic accounts of how the microbiome is involved in depression and Type 2 diabetes, and interacts with viral infection in a non-HIV context, strongly motivate such studies. The main goal of MIBI is therefore to make microbiome and metabolome technology broadly available to HNRC investigators, allowing us to go beyond the 16S rRNA profiling from the NeuroGerm (NG) core in the previous funding period, and focusing on microbiome- related mechanisms of mood and cognitive changes in people with HIV (PWH). To provide insight beyond taxonomic profiling, we will use advanced shotgun metagenomics techniques to read out and assemble bacterial and viral genomes from stool and plasma, and relate these to chemical profiles from untargeted metabolomics, which will also capture drugs and their downstream metabolites and allow us to connect these processes to the microbiome in PWH. Because the microbiome is known to be affected by host genetics, and is likely to interact with viral genotype and titer, close interaction with the other Cores will be essential for enabling researchers to make progress on these questions that require complex multidisciplinary study designs. Additionally, because analysis of highly multivariate microbiome and metabolome data is challenging, an important goal of MIBI will be to provide bioinformatics support and training in how to integrate these data layers with each other and with clinical data important to furthering these scientific aims. The result will be a better understanding of how the microbiome influences and is influenced by long-term HIV infection and co-infections, and how microbiome and metabolome changes may influence individual responses to treatments for HIV and associated conditions (including depressive states and NCI), and ultimately contribute to improved strategies for long-term management of HIV that take the microbiome into account to reduce long-term comorbidities.