Saori Iwase
PhD student; University of Cape Town
Obtained Honours and Master’s degrees in medical science in Japan before moving to South Africa to pursue a PhD at the University of Cape Town, South Africa. Research interests include TB infection, gut microbiome and epigenetic modification among HIV-exposed uninfected infants.
Abstract
Introduction: Infants exposed to HIV (iHEU) have altered immunity compared with HIV-unexposed infants (iHUU) despite not having HIV. As the gut microbiome shapes the developing immune system, we hypothesized that altered microbiome may contribute to this vulnerability. Therefore, we assessed the infant gut microbiota by geographical site and HIV-exposure status and related these to tetanus vaccine titers.
Methods: Infant-mother pairs were recruited from Jos, Nigeria (n=196) and Cape Town, South Africa (n=82). Bacterial DNA was extracted from birth and week 15 stool samples and subjected to 16S rRNA gene sequencing (Illumina Miseq, v3-v4 region). Plasma IgG anti-Tetanus antibody titers were measured by ELISA (TECAN, IBL International GmbH). Data were analyzed using DADA2, phyloseq, DESEq2 and glm.
Results: Socioeconomic status, including mothers’ education level, occupation, and housing, were significantly different between sites (p<0.001). Mothers in Nigeria were older (28 vs 31 years; p=0.001), had higher gravidity (2 vs 3 p<0.001), and were more likely to still exclusively breastfeed at week 15 (61% vs 100%; p<0.001). Both alpha and beta diversity of the infant gut microbiota were strongly influenced by age and site, but less so by HIV-exposure status. Nigerian infants had lower alpha diversity at both time points, which significantly decreased over time, whereas South African infants had an increase in diversity over time. There was a significant increase in Bifidobacterium longum in Nigerian infants during the first 15 weeks of life. At 15 weeks, Bifidobacterium longum was particularly enriched in Nigerian iHUU compared to Nigerian iHEU (p<0.01). There was a stronger correlation between maternal and infant tetanus titers at birth in iHUU compared to iHEU (correlation coefficient: 0.94 vs 0.71). iHUU also showed higher tetanus titers than iHEU at 15 weeks of age. Lastly, a generalized linear model suggested that stool taxa at birth, including Haemophilus parainfluenzae and genus Olsenella, were associated with the Tetanus response at 15 weeks of age, independent of maternal HIV status or other demographic features.
Conclusion: The gut microbial difference was strongly driven by geographical location and infant age. Maternal HIV influenced tetanus titers, but gut microbiota influenced tetanus response independent of HIV-exposure status.