Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responses

Study information

Needs review

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

38230936

DOI Digital object identifier for electronic documents.

10.1128/spectrum.03190-23

URI

https://journals.asm.org/doi/10.1128/spectrum.03190-23

Authors

Iwase SC, Osawe S, Happel A-U, Gray CM, Holmes SP, Blackburn JM, Abimiku A, Jaspan HB

Journal

Microbiology spectrum

Year

2024

Keywords:

HIV-exposed uninfected infants, Nigeria, South Africa, gut microbiota, tetanus toxoid, vaccine response

Infants 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.

Experiment 1

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Curated date: 2024/03/18

Curator: Aishat

Revision editor(s): Aishat

Subjects

Location of subjects: Nigeria; South Africa

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Blood , Blood plasma , Feces Portion of blood,Vertebrate blood,Whole blood,Blood,blood,Blood plasm,Plasma,Portion of blood plasma,Portion of plasma,Blood plasma,blood plasma,Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: HIV infection [X]Human immunodeficiency virus disease,[X]Human immunodeficiency virus disease (disorder),[X]Unspecified human immunodeficiency virus [HIV] disease,[X]Unspecified human immunodeficiency virus [HIV] disease (disorder),HIV - Human immunodeficiency virus infection,HIV INFECT,HIV Infection,HIV infection,HIV Infections,HIV infectious disease,HTLV III INFECT,HTLV III Infections,HTLV III LAV INFECT,HTLV III LAV Infections,HTLV WIII INFECTIONS,HTLV WIII LAV INFECTIONS,HTLV-III Infection,HTLV-III Infections,HTLV-III-LAV Infection,HTLV-III-LAV Infections,HUMAN IMMUNO VIRUS DIS,human immunodeficiency virus,Human immunodeficiency virus [HIV] disease,HUMAN IMMUNOdeficiency VIRUS [HIV] INFECTION,Human immunodeficiency virus caused disease or disorder,Human immunodeficiency virus disease,Human immunodeficiency virus disease (disorder),Human immunodeficiency virus disease or disorder,Human immunodeficiency virus infection,Human immunodeficiency virus infection (disorder),Human immunodeficiency virus infection, NOS,Human immunodeficiency virus infectious disease,human immunodeficiency virus infectious disease,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,LYMPHOTROPIC VIRUS TYPE III INFECTIONS HUMAN T,T LYMPHOTROPIC VIRUS TYPE III INFECT HUMAN,T Lymphotropic Virus Type III Infections, Human,T-Lymphotropic Virus Type III Infections, Human,Unspecified human immunodeficiency virus [HIV] disease (disorder),hIV infection

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Infants who are HIV unexposed and uninfected iHUU

Group 1 name Corresponds to the case (exposed) group for case-control studies: Infants who are HIV exposed but uninfected iHEU

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Infants born to mothers who have HIV but are not infected with HIV

Group 0 sample size Number of subjects in the control (unexposed) group: 76

Group 1 sample size Number of subjects in the case (exposed) group: 202

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: ANCOM; Chi-Square; LASSO Regression; PERMANOVA

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

Signature 1

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Curated date: 2024/03/18

Curator: Aishat

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Source: Figure 1A

Description: Heatmap of the top 20 taxa in the gut microbiota of South African (n = 63) and Nigerian (n = 141) infants in the first week of age. Study site, HIV exposure status, and community cluster types (based on PAM clustering; k = 3)

Abundance in Group 1: increased abundance in Infants who are HIV exposed but uninfected iHEU

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Corynebacterium accolens
Streptococcus pneumoniae
Haemophilus influenzae

Revision editor(s): Aishat

Signature 2

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Mark reviewed

Your review change was submitted

Needs review

Curated date: 2024/03/18

Curator: Aishat

Revision editor(s): Aishat

Source: Figure 1A

Description: Heatmap of the top 20 taxa in the gut microbiota of South African (n = 63) and Nigerian (n = 141) infants in the first week of age. Study site, HIV exposure status, and community cluster types (based on PAM clustering; k = 3)

Abundance in Group 1: decreased abundance in Infants who are HIV exposed but uninfected iHEU

NCBI	Quality Control	Links
Staphylococcus aureus
Staphylococcus epidermidis
Enterococcus faecalis

Revision editor(s): Aishat