Objective: Infants born to mothers infected with human immunodeficiency virus (HIV) experience heightened morbidity and mortality, likely due to systemic immune dysregulation potentially linked to gut microbial dysbiosis. However, the degree of variation in biomarkers and systemic inflammation between HIV-exposed uninfected (HEU) infants and their HIV-unexposed uninfected (HUU) peers remains uncertain.

Materials and Methods: A total of 78 infants, including one set of twins, were enrolled in this study at approximately 6 weeks of age. We collected sociodemographic and clinical data, along with stool samples, to characterize the infant gut microbiota using 16S rRNA gene sequencing. Additionally, whole blood samples were obtained from the infants, and plasma was isolated for MesoScale Discovery (MSD) V-Plex assays to quantify plasma inflammatory and endothelial dysfunction biomarkers.

Results: Among the 78 infants investigated, 35.9% were exposed to HIV in utero and during breastfeeding. At 6 weeks of age, 84.6% of the infants were exclusively breastfed, while 15.4% were mixed-fed with fluids and semi-solids. The gut microbiota comprised predominantly of Bifidobacterium (56.6%), Streptococcus (21.8%), Bacteroides (5.4%), Collinsella (2.8%) and Parabacteroides (2.7%). We did not observe significant differences in infant stool Shannon (p=0.760) and Simpson (p=0.510) indices by infant exposure to maternal HIV. The gut microbiota composition (Bray-Curtis dissimilarity) did not differ between HEU and HUU infants. Furthermore, plasma inflammatory and endothelial dysfunction biomarker levels did not significantly differ between HEU and HUU infants (p>0.05 after multiple test corrections). Notably, several significant positive correlations were observed between inflammatory and endothelial dysfunction biomarker levels (p<0.05). However, no significant associations were found between gut microbial taxa relative abundances and plasma inflammatory or endothelial dysfunction biomarker levels.

Conclusions: Exposure to maternal HIV did not result in any discernible alterations in diversity of the infant gut microbiota, nor in levels of systemic inflammation and endothelial dysfunction biomarkers at 6 weeks of age. Additionally, breastfeeding practice had no significant impact on diversity and composition of the infant gut microbiota. Furthermore, the lack of significant association between taxa relative abundances and systemic inflammation suggests that exposure to HIV and different feeding practices did not significantly influence these parameters in this population.