Evolution of the Gut Microbiome in HIV-Exposed Uninfected and Unexposed Infants during the First Year of Life

HIV-exposed uninfected infants (HEU) have abnormal immunologic functions and increased infectious morbidity in the first 6 months of life, which gradually decreases thereafter. The mechanisms underlying HEU immune dysfunctions are unknown. We hypothesized that unique characteristics of the HEU gut microbiota associated with maternal HIV status may underlie the HEU immunologic dysfunctions. We characterized the infant gut, maternal gut, and breast milk microbiomes of mother-infant pairs, including 123 with HEU and 117 with HIV-uninfected infants (HUU), from South Africa. Pan-bacterial 16S rRNA gene sequencing was performed on (i) infant stool at 6, 28, and 62 weeks; (ii) maternal stool at delivery and 62 weeks; and (iii) breast milk at 6 weeks. Infant gut alpha and beta diversities were similar between groups. Microbial composition significantly differed, including 12 genera, 5 families and 1 phylum at 6 weeks; 12 genera and 2 families at 28 weeks; and 2 genera and 2 families at 62 weeks of life. Maternal gut microbiomes significantly differed in beta diversity and microbial composition, and breast milk microbiomes differed in microbial composition only. Infant gut microbiotas extensively overlapped with maternal gut and minimally with breast milk microbiotas. Nevertheless, exclusively breastfed HEU and HUU had less divergent microbiomes than nonexclusively breastfed infants. Feeding pattern and maternal gut microbiome imprint the HEU gut microbiome. Compared to HUU, the HEU gut microbiome prominently differs in early infancy, including increased abundance of taxa previously observed to be present in excess in adults with HIV. The HEU and HUU gut microbiome compositions converge over time, mirroring the kinetics of HEU infectious morbidity risk.