This thesis of Yue Zhang investigates the relationships between gut microbiome, aging, and immune dysfunction through parallel studies in the general population and people living with HIV (PLHIV). Aging leads to immune decline with reduced naïve T-cells, increased senescent cells, and chronic inflammation, alongside metabolic alterations. The research reveals how microbiome studies in aging and HIV infection are interconnected: aging-related findings benefit PLHIV, while HIV serves as a model of accelerated aging, offering insights applicable to the general population.
Through advanced bioinformatics analyses, we identified bacterial changes associated with aging and HIV infection, integrating these findings with health metrics, metabolites, and inflammatory markers. Key contributions include: (1) identifying 'geroprotective' bacterial genes that increase with age while associating with lower frailty and beneficial metabolites; (2) revealing distinct Prevotella copri strains with different immunomodulatory capacities in PLHIV versus controls; and (3) uncovering connections between HIV-associated gut dysbiosis and dysregulated tryptophan metabolism.
