Neonates exposed to HIV but uninfected exhibit an altered gut microbiota and inflammation associated with impaired breast milk antibody function

BackgroundInfants exposed to HIV but uninfected have altered immune profiles which include heightened systemic inflammation. The mechanism(s) underlying this phenomenon is unknown. Here, we investigated differences in neonatal gut bacterial and viral microbiome and associations with inflammatory biomarkers in plasma. Further, we tested whether HIV exposure impacts antibody-microbiota binding in neonatal gut and whether antibodies in breast milk impact the growth of commensal bacteria.ResultsNeonates exposed to HIV but uninfected (nHEU) exhibited altered gut bacteriome and virome compared to unexposed neonates (nHU). In addition, HIV exposure differentially impacted IgA-microbiota binding in neonates. The relative abundance of Blautia spp. in the whole stool or IgA-bound microbiota was positively associated with plasma concentrations of C-reactive protein. Finally, IgA from the breast milk of mothers living with HIV displayed a significantly lower ability to inhibit the growth of Blautia coccoides which was associated with inflammation in nHEU.ConclusionnHEU exhibits profound alterations in gut bacterial microbiota with a mild impact on the enteric DNA virome. Elevated inflammation in nHEU could be due to a lower capacity of breast milk IgA from mothers living with HIV to limit growth the of gut bacteria associated with inflammation.BDUn311MBkuDfDvveFNavEVideo AbstractConclusionnHEU exhibits profound alterations in gut bacterial microbiota with a mild impact on the enteric DNA virome. Elevated inflammation in nHEU could be due to a lower capacity of breast milk IgA from mothers living with HIV to limit growth the of gut bacteria associated with inflammation.BDUn311MBkuDfDvveFNavEVideo Abstract