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Innate Immune Responses and Gut Microbiomes Distinguish HIV-Exposed from HIV-Unexposed Children in a
Nelly Amenyogbe1,2, Pedro Dimitriu3, Patricia Cho4
1Department of Experimental Medicine, The University of British Columbia, Vancouver, British Columbia V5Z 1M9, Canada; n.akuvy@gmail.com wmohn@mail.ubc.ca.
Insights
Children born to mothers with HIV (HEU) show altered immunity and gut microbiomes, varying by geographic location. Maternal HIV infection impacts HEU children
Area of Science:
- Immunology
- Microbiology
- Global Health
Background:
- Children born to HIV-positive mothers who are HIV-negative (HEU) exhibit increased infection susceptibility compared to unexposed children (HUU).
- Innate immunity and gut microbiome composition differ geographically and influence each other.
- The interplay between maternal HIV, geographic location, and immune-microbiome profiles in HEU children remains understudied.
Purpose of the Study:
- To investigate biogeographical immune-microbiome correlations in HEU children.
- To compare innate immune responses and stool microbiomes of HEU and HUU children across Belgium, Canada, and South Africa.
- To test if region-specific immune alterations correlate with microbiome differences in HEU children.
Main Methods:
- Comparative analysis of innate immune responses and stool microbiome composition.
- Study included 2-year-old HEU and HUU children from distinct global settings.
- Statistical analysis to identify immune-microbiome associations.
Main Results:
- No universal immune or microbiome signature distinguished HEU from HUU children across all populations.
- Population-specific differences in stool microbiomes were observed, including reduced short-chain fatty acid-producing bacteria in Canadian HEU children.
- No consistent innate immune-microbiome associations differentiating HEU from HUU children were found in any population.
Conclusions:
- Maternal HIV infection is associated with population-specific alterations in both innate immunity and the gut microbiome of HEU children.
- Geographic location plays a significant role in shaping these immune and microbiome differences.
- Findings highlight the complex, location-dependent impact of maternal HIV on child health outcomes.
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.
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