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Feeding-related gut microbial composition associates with peripheral T cell activation and mucosal gene expression in African infants.

Background: Exclusive breastfeeding reduces the rate of postnatal HIV transmission compared to non-exclusive breastfeeding, however the mechanisms of this protection are unknown. Our study was designed to interrogate the mechanisms underlying the protective effect of exclusive breastfeeding (EBF).

Methods: A prospective, longitudinal study of infants from a high HIV prevalence, low-income setting in South Africa. We evaluated the role of any non-breastmilk feeds excluding prescribed medicines. Our primary outcomes were stool microbial communities via 16S rRNA gene sequencing, peripheral T cell activation via flow cytometry, and buccal mucosal gene expression via quantitative PCR.

Results: 155 infants were recruited at birth with mean gestational age and birth weights of 38.9 weeks and 3.2 kgs respectively. All infants were EBF at birth, but only 43.5% and 20% remained EBF at 6 or 14 weeks of age, respectively. We observed lower stool microbial diversity and distinct microbial composition in exclusive breastfed infants. These microbial communities, and the relative abundance of key taxa, were correlated with peripheral CD4+ T cell activation, which was lower in exclusive breastfeeding infants. In the oral mucosa, gene expression of chemokine and chemokine receptors involved in recruitment of HIV target cells to tissues, as well as epithelial cytoskeletal proteins, was lower in exclusive breastfeeding infants.

Conclusions: These data suggest that non-exclusive breastfeeding alters the gut microbiota, increasing T cell activation and, potentially, mucosal recruitment of HIV target cells. Study findings highlight a biologically plausible mechanistic explanation for the reduced postnatal HIV transmission observed in EBF infants.

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