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Clin Infect Dis. 2018 Sep 28;67(8):1237-1246. doi: 10.1093/cid/ciy265.

Feeding-Related Gut Microbial Composition Associates With Peripheral T-Cell Activation and Mucosal Gene Expression in African Infants.

Author information

1
University of Washington Schools of Medicine and Public Health, Seattle.
2
Duke University, Durham, North Carolina.
3
Institute of Infectious Disease and Molecular Medicine, University of Cape Town Health Sciences Faculty, South Africa.
4
Earth and Environmental Science, Lawrence Berkeley National Laboratories, Berkeley.
5
University of California, Berkeley.
6
National Health Laboratory Services, Cape Town, South Africa.
7
Desmond Tutu TB Centre, Stellenbosch University, Cape Town, South Africa.
8
Fred Hutchinson Cancer Research Center, Seattle, Washington.
9
Columbia University, New York, New York.
10
Center for Infectious Disease Research, Washington.
11
Seattle Children's Research Institute, Washington.

Abstract

Background:

Exclusive breastfeeding reduces the rate of postnatal human immunodeficiency virus (HIV) transmission compared to nonexclusive breastfeeding; however, the mechanisms of this protection are unknown. Our study aimed to interrogate the mechanisms underlying the protective effect of exclusive breastfeeding.

Methods:

We performed a prospective, longitudinal study of infants from a high-HIV-prevalence, low-income setting in South Africa. We evaluated the role of any non-breast milk feeds, excluding prescribed medicines on stool microbial communities via 16S rRNA gene sequencing, peripheral T-cell activation via flow cytometry, and buccal mucosal gene expression via quantitative polymerase chain reaction assay.

Results:

A total of 155 infants were recruited at birth with mean gestational age of 38.9 weeks and mean birth weight of 3.2 kg. All infants were exclusively breastfed (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 exclusively breastfed infants. These microbial communities, and the relative abundance of key taxa, were correlated with peripheral CD4+ T-cell activation, which was lower in EBF 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 EBF infants.

Conclusions:

These data suggest that nonexclusive 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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