Dynamics of the infant gut microbiota in the first 18 months of life: the impact of maternal HIV infection and breastfeeding

Abstract

Background Access to antiretroviral therapy (ART) during pregnancy and breastfeeding for mothers with HIV has resulted in fewer children acquiring HIV peri- and postnatally, resulting in an increase in the number of children who are exposed to the virus but are not infected (HEU). HEU infants have an increased likelihood of childhood infections and adverse growth outcomes, as well as increased mortality compared to their HIV-unexposed (HUU) peers. We explored potential differences in the gut microbiota in a cohort of 272 Nigerian infants born to HIV-positive and negative mothers in this study during the first 18 months of life. Results The taxonomic composition of the maternal vaginal and gut microbiota showed no significant differences based on HIV status, and the composition of the infant gut microbiota at birth was similar between HUU and HEU. Longitudinal taxonomic composition of the infant gut microbiota and weight-for-age z-scores (WAZ) differed depending on access to breast milk. HEU infants displayed overall lower WAZ than HUU infants at all time points. We observed a significantly lower relative abundance of Bifidobacterium in HEU infants at 6 months postpartum. Breast milk composition also differed by time point and HIV infection status. The antiretroviral therapy drugs, lamivudine and nevirapine, as well as kynurenine, were significantly more abundant in the breast milk of mothers with HIV. Levels of tiglyl carnitine (C5) were significantly lower in the breast milk of mothers without HIV. ART drugs in the breast milk of mothers with HIV were associated with a lower relative abundance of Bifidobacterium longum. Conclusions Maternal HIV infection was associated with adverse growth outcomes of HEU infants in this study, and these differences persist from birth through at least 18 months, which is a critical window for the development of the immune and central nervous systems. We observed that the relative abundance of Bifidobacterium spp. was significantly lower in the gut microbiota of all HEU infants over the first 6 months postpartum, even if HEU infants were receiving breast milk. Breastfeeding was of benefit in our HEU infant cohort in the first weeks postpartum; however, ART drug metabolites in breast milk were associated with a lower abundance of Bifidobacterium.

Age-specific associations with dental caries in HIV-infected, exposed but uninfected and HIV-unexposed uninfected children in Nigeria

“…It is likely that HUU children in this study population might have heightened levels of unmeasured risk factors that include nutritional status, immunological markers and genetics associated with caries compared to HI and HEU children. In addition, although speculative, it is reasonable to posit as a hypothesis that the development and training of the immune system via the oral microbiota [ 20 ], and perhaps the gut microbiota [ 58 ], in HEU children via maternal ART exposure in-utero and lower likelihood of breast feeding (observed in mothers of HEU children) might be protective of caries [ 4 ]. Our thoughts are based on results from a previous analysis of younger children suggesting a higher odds of caries in children delivered after a spontaneous membrane rupture and in those who were breastfed for longer durations [ 4 ].…”

Bifidobacterium infantis associates with T cell immunity in human infants and is sufficient to enhance antigen-specific T cells in mice

“…Previous studies have profiled vaccine responses in HIV-exposed versus unexposed infants ( 40 , 41 ), but none has dissected the causal role of the gut microbiota within iHEU in driving the spectrum of immune alterations, despite reports of their altered gut microbiota ( 12 , 42 ). Binarizing infants into HRs versus LRs allowed us to assess microbiota variation within iHEU and tease out the effects of gut microbes on immunity independent of other potential confounders such as antiretroviral post-exposure prophylaxis, which may associate with immune phenotypes.…”

Infant feeding: emerging concepts to prevent HIV transmission

“…This study reconfirmed higher maternal viraemia during breastfeeding to be associated with increased transmission risk [11 && ]. Maternal HIV and/or ART (or other antimicrobials) may affect breastmilk composition and the infant microbiome [12,13] with potential implications for infant health, growth and development. How this impacts HIV transmission risk remains to be determined.…”