Key Points
Innate immune and stool microbiome signatures of HEU children are region specific.
Differences in HEU immune responses were unrelated to the microbiome.
Future immune studies of HEU children must be studied across diverse settings.
Abstract
In both high- and low-income countries, HIV-negative children born to HIV-positive mothers (HIV exposed, uninfected [HEU]) are more susceptible to severe infection than HIV-unexposed, uninfected (HUU) children, with altered innate immunity hypothesized to be a cause. Both the gut microbiome and systemic innate immunity differ across biogeographically distinct settings, and the two are known to influence each other. And although the gut microbiome is influenced by HIV infection and may contribute to altered immunity, the biogeography of immune-microbiome correlations among HEU children have not been investigated. To address this, we compared the innate response and the stool microbiome of 2-y-old HEU and HUU children from Belgium, Canada, and South Africa to test the hypothesis that region-specific immune alterations directly correlate to differences in their stool microbiomes. We did not detect a universal immune or microbiome signature underlying differences between HEU versus HUU that was applicable to all children. But as hypothesized, population-specific differences in stool microbiomes were readily detected and included reduced abundances of short-chain fatty acid–producing bacteria in Canadian HEU children. Furthermore, we did not identify innate immune-microbiome associations that distinguished HEU from HUU children in any population. These findings suggest that maternal HIV infection is independently associated with differences in both innate immunity and the stool microbiome in a biogeographical population-specific way.
Footnotes
This work was supported by grants from the Canadian Institutes of Health Research (PJT-148781 and HET-85515) and The University of British Columbia (F0906208).
The sequences presented in this article have been submitted to the National Center for Biotechnology Information Sequence Read Archive (https://www.ncbi.nlm.nih.gov/bioproject/) under accession number PRJNA660015.
The online version of this article contains supplemental material.
- Received January 14, 2020.
- Accepted September 15, 2020.
- Copyright © 2020 by The American Association of Immunologists, Inc.
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