HIV-exposed uninfected (HEU) infants in resource-limited settings experience higher morbidity and mortality from infectous casuses compared with infants born to HIV-uninfected women, suggesting an immune dysregulation despite remaining HIV-uninfected. In infancy, immune system function and development are reliant upon the evolution of gut microbiota. However, this evolution, along with its impact on the immune system, has not been studied among HEU infants. Dysbiosis in the evolution of gut microbiota among HEU infants may be a significant contributor to higher HEU infant and child mortality. With the HEU population expanding at over 1 million infants per year in resouce-limited settings, it is of great public health importance to identify biologically plausible, modifiable risk factorsfor higher mortality.
The aims of this study Botswana based study are: 1. To describe the evolution of the gut microbiome at birth, 3, 6, 9, and 12 months of life among 40 HEU breastfed infants compared with 40 HUU breastfed infants. 2. To assess for differences in innate and adaptive immune function and soluble markers of immune activation at 3, 6, and 9 months of life between HEU and HUU infants and correlate immune profiles with enteric microbiota profiles. 3. Among HIV-infected and HIV-uninfected mothers, to compare vaginal, rectal and breast milk microbiome at delivery, and breast milk microbiome 1 month postpartum, between HIV- infected and HIV-uninfected mothers of infants enrolled in the study.
Although more than 1 million infants born to HIV-infected women in resource-limited settings remain HIV uninfected themselves, they experience higher morbidity and mortality from infectious causes compared with infants born to HIV-negative women, possibly related to an abnormal gut microbiome acquired from an immunocompromised mother. This study would be the first to 1) characterize stool microbiome evolution in the first year of life, comparing HIV- exposed uninfected infants to HIV-unexposed infants in Botswana, and 2) measure the potential impacts of this microbiome on infants' immune system functioning and development.