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...

Full description

Bibliographic Details
Main Authors: Saori C. Iwase, Sophia Osawe, Anna-Ursula Happel, Clive M. Gray, Susan P. Holmes, Jonathan M. Blackburn, Alash'le Abimiku, Heather B. Jaspan
Format: Article
Language:English
Published: American Society for Microbiology 2024-02-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/spectrum.03190-23
_version_ 1797322797222985728
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
format Article
id doaj.art-def87cd9e69c4d0baa3cd6082d15c7e7
institution Directory Open Access Journal
issn 2165-0497
language English
last_indexed 2024-03-08T05:19:26Z
publishDate 2024-02-01
publisher American Society for Microbiology
record_format Article
series Microbiology Spectrum
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
work_keys_str_mv AT saoriciwase longitudinalgutmicrobiotacompositionofsouthafricanandnigerianinfantsinrelationtotetanusvaccineresponses
AT sophiaosawe longitudinalgutmicrobiotacompositionofsouthafricanandnigerianinfantsinrelationtotetanusvaccineresponses
AT annaursulahappel longitudinalgutmicrobiotacompositionofsouthafricanandnigerianinfantsinrelationtotetanusvaccineresponses
AT clivemgray longitudinalgutmicrobiotacompositionofsouthafricanandnigerianinfantsinrelationtotetanusvaccineresponses
AT susanpholmes longitudinalgutmicrobiotacompositionofsouthafricanandnigerianinfantsinrelationtotetanusvaccineresponses
AT jonathanmblackburn longitudinalgutmicrobiotacompositionofsouthafricanandnigerianinfantsinrelationtotetanusvaccineresponses
AT alashleabimiku longitudinalgutmicrobiotacompositionofsouthafricanandnigerianinfantsinrelationtotetanusvaccineresponses
AT heatherbjaspan longitudinalgutmicrobiotacompositionofsouthafricanandnigerianinfantsinrelationtotetanusvaccineresponses