It is already known that a reduction in gut microbial richness is the hallmark change of human immunodeficiency virus (HIV) infection, but how this dysbiosis is established in the HIV-exposed uninfected infant is poorly understood. A recent cross-sectional study, led by Dr. Grace M. Aldrovandi from the Children’s Hospital Los Angeles in Los Angeles (USA), suggests that perturbations in the infant gut microbiome may explain the greater risk of morbidity and mortality in uninfected babies born to HIV-positive mothers.
Most children born to HIV-infected women do not acquire HIV infection, but they experience twice the mortality of children born to HIV-negative women. As establishment of a healthy microbiome in infants influences the development of a healthy infant metabolism and immunity, the researchers hypothesized that the perturbation of both the mother’s microbiome and the mother’s breast milk human milk oligosaccharide (HMO) composition by HIV infection may alter the microbiome in HIV-exposed uninfected infants and could account for their increased morbidity and mortality rates. Note that HMOs are the third largest constituent of human milk and are not digested by the infant, therefore acting as a prebiotic that nourishes the infant microbiome.
To test this theory, 50 mother and infant pairs from Port-au-Prince, Haiti, were enrolled, evenly split between HIV-positive and HIV-negative mothers (25 HIV+ mothers and 25 HIV- mothers). The researchers analysed the microbiomes from six different body sites from each pair (mother: areolar skin, breast milk, and vagina; infant: mouth, skin, and stool). One infant born to a HIV-positive mother subsequently acquired HIV infection and this mother-infant dyad was excluded.
Although HIV infection did not have significant effects on the maternal microbiome, the mother’s HIV infection influenced the infant microbiome. It was found that the microbiomes of uninfected infants born to HIV-positive mothers were significantly different from infants born to HIV-negative women in the same community. The relative microbial maturity of the HIV-exposed uninfected infants’ stool was significantly lower than that observed in the infants born to HIV-negative women. The bacterial composition of infant stool was the most altered on the basis of the mother’s HIV status. Changes at the family level included higher populations of Prevotellaceae, Desulfovibrionaceae, and Alcaligenaceae in the stool of non-exposed uninfected infants compared to that of HIV-exposed uninfected infants.
As the gut bacterial communities of mothers with and without HIV infection in the cohort were relatively similar, perturbations in the infants’ gut microbiomes were not completely explained by the mother-to-infant transfer. The researchers characterized milk oligosaccharide composition in breast milk samples from HIV-infected and uninfected mothers. HMO composition of breast milk was altered in HIV-positive compared to HIV-negative women. It is also worth mentioning that specific HMOs in breast milk correlated with the infant stool bacteria. These correlations were distinct and dependent on the mother’s HIV status, which shows that the infant microbiome was disrupted based on maternal HIV infection. In this line, a previous study has found that higher concentrations of HMOs in milk were associated with protection against postnatal HIV transmission, independent of other known risk factors.
To sum up, maternal HIV infection is associated with changes in the microbiome of HIV-exposed uninfected infants and human breast milk oligosaccharides in the mothers were associated with specific bacterial species in these high-risk infants. This infants’ microbiome dysbiosis may contribute to the increases morbidity and mortality observed for HIV-exposed uninfected infants. Long-term outcomes of changes to the infant’s microbiome should be studied.
Bender JM, Li F, Martelly S, et al. Maternal HIV infection influences the microbiome of HIV-uninfected infants. Sci Transl Med. 2016; 8(349):349ra100. doi:10.1126/scitranslmed.aaf5103.
Bode L, Kuhn L, Kim HY, et al. Human milk oligosaccharide concentration and risk of postnatal transmission of HIV through breastfeeding. Am J Clin Nutr. 2012; 96(4):831-9. doi: 10.3945/ajcn.112.039503.