The impact of in utero HIV exposure on gut microbiota, inflammation, and microbial translocation

Abstract

HIV-exposed but uninfected (HEU) children represent a growing population and show a significantly higher number of infectious diseases, several immune alterations, compromised growth, and increased mortality rates when compared to HIV-unexposed children. Considering the impact that the gut microbiota has on general host homeostasis and immune system development and modulation, we hypothesized that HEU children present altered gut microbiota that is linked to the increased morbidity and the immune system disorders faced by them. Our experiments revealed no differences in beta and alpha diversity of the gut microbiota between HEU and unexposed children or between HIV-infected and uninfected mothers. However, there were differences in the abundance of several taxa from the gut microbiota between HEU and unexposed children and between HIV-infected and uninfected mothers. Functional prediction based on 16S rRNA sequences also indicated differences between HEU and unexposed children and between infected and uninfected mothers. In addition, we detected no differences between HEU and unexposed children in relation to weight, weight-for-age z scores, albumin serum levels, or microbial translocation and inflammation markers. In summary, HIV-infected mothers and their HIV-exposed children present alterations in the abundance of several taxa in the gut microbiome and the predicted functional metagenome when compared to uninfected mothers and unexposed children. Knowledge about the gut microbiome of HEU children in different settings is essential in order to determine better treatments for this susceptible population.

Keywords: 16S rRNA; HIV; children; exposed uninfected; gut microbiota; inflammation; microbial translocation.

Figure 1.

Gut microbiome of mothers and children. Principal coordinate analysis (PCoA) of Bray Curtis distances among groups of children and mothers (a); Richness (Chao1) and diversity (Shannon and Simpson) indexes (b); Relative abundance at the family level for groups of mothers and children (c); Mean source proportions of bacteria from the children’s gut microbiota (d).

Figure 2.

Differentially abundant OTUs in the gut microbiome of mothers and children. Log 2-fold change of differentially abundant OTUs between children (a) and mothers (b) categorized by the highest taxonomic level identified. Each dot corresponds to an OTU. “o” = Order; “f” = Family; “g” = Genera.

Figure 3.

Food and microbiota diversity relationship. Weekly frequency of food consumption for children (a) and mothers (b). Relationship between consumption of individual food items and richness and diversity estimates for children (c) and mothers (d). Bar plots represent the Bray Curtis beta diversity explained variation for each food item from the food frequency questionnaire. The heatmap represents the correlation coefficients of food items and richness (Chao1) and diversity (Shannon and Simpson) estimates.

Figure 4.

Determination of microbial translocation and inflammation markers in plasma from children and mothers. Inflammatory cytokines (a) and C-reactive protein (b) in children; inflammatory cytokines (c) in mothers; lipopolysaccharide-binding protein (LBP) (d) and soluble CD14 (sCD14) (e) for mothers and children.