Research
Gut microbiota and clinical outcomes in infants exposed to HIV
Infants exposed to HIV but uninfected (iHEU), display heightened immune activation, inflammation, compromised growth and are at an elevated risk of neurodevelopmental delay compared to those who are HIV unexposed and uninfected(iHUU). The biological mechanisms driving these disparities remain poorly understood. Our lab studies how early-life gut microbial exposures shape infant immune and developmental outcomes in iHEU. We combine analyses of longitudinal mother–infant cohort samples with mechanistic studies in gnotobiotic and preclinical models to define causal pathways linking the gut microbiota of iHEU with immune development, growth and neurodevelopmental phenotypes.
Our long-term goal is to identify mechanisms driving adverse outcomes in iHEU and develop microbiota-targeted strategies to improve child health.
1. Causal effect of early life gut microbiota on development in iHEU
We and others have shown that iHEU display altered gut microbiota compared to iHUU during early life. However, whether these microbial alterations directly contribute to impaired immune development, growth deficits, or neurodevelopmental delays remains unknown.
We are testing the hypothesis that early life gut microbiota from iHEU causally influences host developmental trajectories. impairs immune development, growth and neurodevelopment. Using gnotobiotic mouse models colonized with stool from iHEU infants, we investigate how early life gut microbiota shapes immune development and inflammatory response, growth and skeletal development as well as neurodevelopmental outcomes.
These studies aim to identify early life microbial communities that contribute to altered developmental phenotypes in iHEU.
2. Effect of maternal antiretroviral exposure on the infant gut bacteriome, virome, and development
In addition to HIV exposure, iHEU are exposed to combination antiretroviral therapy (cART) during pregnancy and breastfeeding, as well as postnatal antiretroviral prophylaxis during early life. Although ART has dramatically reduced vertical transmission of HIV, its effect on infant microbial ecology and developmental biology remains incompletely understood.
Some antiretrovirals have been shown to display antibacterial activity in vitro suggesting that antiretrovirals may directly impact early life gut microbial communities. Such perturbations may influence immune maturation, metabolism, growth and neurodevelopment.
Using animal models, we investigate how maternal cART and neonatal antiretroviral prophylaxis affect infant gut bacteriome and virome, immune development, growth and neurodevelopment in the offspring.
These studies aim to disentangle the effect of antiretroviral exposure from those by other factors such as maternal inflammation, immune activation and HIV exposure and define potential direct effects of ART exposure on developmental phenotypes during early life.