Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responses
ABSTRACTInfants who are exposed to HIV but uninfected (iHEU) have higher risk of infectious morbidity than infants who are HIV-unexposed and uninfected (iHUU), possibly due to altered immunity. As infant gut microbiota may influence immune development, we evaluated the effects of HIV exposure on inf...
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Format: | Article |
Language: | English |
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American Society for Microbiology
2024-02-01
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Series: | Microbiology Spectrum |
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Online Access: | https://journals.asm.org/doi/10.1128/spectrum.03190-23 |
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author | Saori C. Iwase Sophia Osawe Anna-Ursula Happel Clive M. Gray Susan P. Holmes Jonathan M. Blackburn Alash'le Abimiku Heather B. Jaspan |
author_facet | Saori C. Iwase Sophia Osawe Anna-Ursula Happel Clive M. Gray Susan P. Holmes Jonathan M. Blackburn Alash'le Abimiku Heather B. Jaspan |
author_sort | Saori C. Iwase |
collection | DOAJ |
description | ABSTRACTInfants who are exposed to HIV but uninfected (iHEU) have higher risk of infectious morbidity than infants who are HIV-unexposed and uninfected (iHUU), possibly due to altered immunity. As infant gut microbiota may influence immune development, we evaluated the effects of HIV exposure on infant gut microbiota and its association with tetanus toxoid vaccine responses. We evaluated the gut microbiota of 82 South African (61 iHEU and 21 iHUU) and 196 Nigerian (141 iHEU and 55 iHUU) infants at <1 and 15 weeks of life by 16S rRNA gene sequencing. Anti-tetanus antibodies were measured by enzyme-linked immunosorbent assay at matched time points. Gut microbiota in the 278 included infants and its succession were more strongly influenced by geographical location and age than by HIV exposure. Microbiota of Nigerian infants, who were exclusively breastfed, drastically changed over 15 weeks, becoming dominated by Bifidobacterium longum subspecies infantis. This change was not observed among South African infants, even when limiting the analysis to exclusively breastfed infants. The Least Absolute Shrinkage and Selection Operator regression suggested that HIV exposure and gut microbiota were independently associated with tetanus titers at week 15, and that high passively transferred antibody levels, as seen in the Nigerian cohort, may mitigate these effects. In conclusion, in two African cohorts, HIV exposure minimally altered the infant gut microbiota compared to age and setting, but both specific gut microbes and HIV exposure independently predicted humoral tetanus vaccine responses.IMPORTANCEGut microbiota plays an essential role in immune system development. Since infants HIV-exposed and uninfected (iHEU) are more vulnerable to infectious diseases than unexposed infants, we explored the impact of HIV exposure on gut microbiota and its association with vaccine responses. This study was conducted in two African countries with rapidly increasing numbers of iHEU. Infant HIV exposure did not substantially affect gut microbial succession, but geographic location had a strong effect. However, both the relative abundance of specific gut microbes and HIV exposure were independently associated with tetanus titers, which were also influenced by baseline tetanus titers (maternal transfer). Our findings provide insight into the effect of HIV exposure, passive maternal antibody, and gut microbiota on infant humoral vaccine responses. |
first_indexed | 2024-03-08T05:19:26Z |
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institution | Directory Open Access Journal |
issn | 2165-0497 |
language | English |
last_indexed | 2024-03-08T05:19:26Z |
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spelling | doaj.art-def87cd9e69c4d0baa3cd6082d15c7e72024-02-06T14:04:54ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972024-02-0112210.1128/spectrum.03190-23Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responsesSaori C. Iwase0Sophia Osawe1Anna-Ursula Happel2Clive M. Gray3Susan P. Holmes4Jonathan M. Blackburn5Alash'le Abimiku6Heather B. Jaspan7Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South AfricaInstitute of Human Virology-Nigeria, Abuja, NigeriaDivision of Immunology, Department of Pathology, University of Cape Town, Cape Town, South AfricaDivision of Molecular Biology and Human Genetics, Biomedical Research Institute, Stellenbosch University, Cape Town, South AfricaDepartment of Statistics, Stanford University, Stanford, California, USAInstitute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South AfricaInstitute of Human Virology-Nigeria, Abuja, NigeriaDivision of Immunology, Department of Pathology, University of Cape Town, Cape Town, South AfricaABSTRACTInfants who are exposed to HIV but uninfected (iHEU) have higher risk of infectious morbidity than infants who are HIV-unexposed and uninfected (iHUU), possibly due to altered immunity. As infant gut microbiota may influence immune development, we evaluated the effects of HIV exposure on infant gut microbiota and its association with tetanus toxoid vaccine responses. We evaluated the gut microbiota of 82 South African (61 iHEU and 21 iHUU) and 196 Nigerian (141 iHEU and 55 iHUU) infants at <1 and 15 weeks of life by 16S rRNA gene sequencing. Anti-tetanus antibodies were measured by enzyme-linked immunosorbent assay at matched time points. Gut microbiota in the 278 included infants and its succession were more strongly influenced by geographical location and age than by HIV exposure. Microbiota of Nigerian infants, who were exclusively breastfed, drastically changed over 15 weeks, becoming dominated by Bifidobacterium longum subspecies infantis. This change was not observed among South African infants, even when limiting the analysis to exclusively breastfed infants. The Least Absolute Shrinkage and Selection Operator regression suggested that HIV exposure and gut microbiota were independently associated with tetanus titers at week 15, and that high passively transferred antibody levels, as seen in the Nigerian cohort, may mitigate these effects. In conclusion, in two African cohorts, HIV exposure minimally altered the infant gut microbiota compared to age and setting, but both specific gut microbes and HIV exposure independently predicted humoral tetanus vaccine responses.IMPORTANCEGut microbiota plays an essential role in immune system development. Since infants HIV-exposed and uninfected (iHEU) are more vulnerable to infectious diseases than unexposed infants, we explored the impact of HIV exposure on gut microbiota and its association with vaccine responses. This study was conducted in two African countries with rapidly increasing numbers of iHEU. Infant HIV exposure did not substantially affect gut microbial succession, but geographic location had a strong effect. However, both the relative abundance of specific gut microbes and HIV exposure were independently associated with tetanus titers, which were also influenced by baseline tetanus titers (maternal transfer). Our findings provide insight into the effect of HIV exposure, passive maternal antibody, and gut microbiota on infant humoral vaccine responses.https://journals.asm.org/doi/10.1128/spectrum.03190-23HIV-exposed uninfected infantsSouth AfricaNigeriagut microbiotatetanus toxoidvaccine response |
spellingShingle | Saori C. Iwase Sophia Osawe Anna-Ursula Happel Clive M. Gray Susan P. Holmes Jonathan M. Blackburn Alash'le Abimiku Heather B. Jaspan Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responses Microbiology Spectrum HIV-exposed uninfected infants South Africa Nigeria gut microbiota tetanus toxoid vaccine response |
title | Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responses |
title_full | Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responses |
title_fullStr | Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responses |
title_full_unstemmed | Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responses |
title_short | Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responses |
title_sort | longitudinal gut microbiota composition of south african and nigerian infants in relation to tetanus vaccine responses |
topic | HIV-exposed uninfected infants South Africa Nigeria gut microbiota tetanus toxoid vaccine response |
url | https://journals.asm.org/doi/10.1128/spectrum.03190-23 |
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