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Gut microbiota and immunity in infants exposed to HIV

Infants exposed to HIV but not infected (iHEU), display heightened immune activation, inflammation and have high infectious morbidity compared to those who are HIV unexposed (iHU). The mechanisms behind these phenomena are not well understood. We are evaluating if there is a causal relationship between early life gut microbiota in iHEU and these immune outcomes. We perform clinical research using samples obtained from human cohorts and conduct follow up reverse translational studies using preclinical models to gain mechanistic insights. Our goal is to unravel mechanisms that underlie poorer health outcomes in iHEU which will guide development of microbiota-targeted interventions to improve health outcomes in these infants.

Gut microbiota and inflammatory biomarkers in neonates who are HIV-exposed but uninfected (nHEU) compared to those who are HIV-unexposed (nHU). (A) Differentially abundant gut bacteria between nHU and nHEU. (B) Plasma concentration of CRP.

Project 1:

We are testing the hypothesis that the gut microbiota early in life in iHEU causes elevated inflammation and impairs immune development using gnotobiotic murine models.

Project 2:

iHEU are exposed to HIV and combined antiretroviral medication in utero and during breast feeding. While combined antiretroviral therapy is effective in suppressing viral replication, these medication may have unintended secondary effects, highlighting the need for further follow-up research. We are investigating the impact of maternal combination antiretroviral therapy on the enteric microbiota and inflammatory responses in offspring.