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

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Reviewed Marked as Reviewed by Svetlana up on 2024-6-25
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
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


Reviewed Marked as Reviewed by Svetlana up on 2024-6-25

Curated date: 2024/03/18

Curator: Aishat

Revision editor(s): Aishat, Victoria, Scholastica

Subjects

Location of subjects
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
Feces 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
Gut microbiome measurement Gut microbiome measurement,gut microbiome measurement
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Infants who are HIV unexposed and uninfected (iHUU) at week 1
Group 1 name Corresponds to the case (exposed) group for case-control studies
Infants who are HIV exposed but uninfected (iHEU) at week 1
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Infants at 1 week of age born to mothers from South Africa who have HIV but are not themselves infected with HIV
Group 0 sample size Number of subjects in the control (unexposed) group
21
Group 1 sample size Number of subjects in the case (exposed) group
61
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
None

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).
centered log-ratio
Statistical test
ANCOM
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-6-25

Curated date: 2024/03/18

Curator: Aishat

Revision editor(s): Aishat, Scholastica

Source: Table 2

Description: Differentially abundant ASVs (adj P < 0.05) among iHEU (infants who are HIV exposed but uninfected) relative to iHUU (infants who are HIV unexposed and uninfected) at 1 week of age in South Africa

Abundance in Group 1: increased abundance in Infants who are HIV exposed but uninfected (iHEU) at week 1

NCBI Quality ControlLinks
Klebsiella variicola
unclassified Sutterella
unclassified Holdemanella
Parabacteroides merdae
unclassified Catenibacterium
Blautia obeum
unclassified Senegalimassilia
Bifidobacterium breve
Klebsiella quasipneumoniae
unclassified Parolsenella
unclassified Blautia
[Ruminococcus] torques
Collinsella aerofaciens
unclassified Subdoligranulum
Phocaeicola vulgatus
Klebsiella pneumoniae
unclassified Megamonas
Romboutsia ilealis
unclassified Faecalibacterium
Fusobacterium mortiferum
Enterococcus faecium
Parabacteroides distasonis

Revision editor(s): Aishat, Scholastica

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-6-25

Curated date: 2024/03/18

Curator: Aishat

Revision editor(s): Aishat, Scholastica

Source: Table 2

Description: Differentially abundant ASVs (adj P < 0.05) among iHEU (infants who are HIV exposed but uninfected) relative to iHUU (infants who are HIV unexposed and uninfected) at 1 week of age in South Africa

Abundance in Group 1: decreased abundance in Infants who are HIV exposed but uninfected (iHEU) at week 1

NCBI Quality ControlLinks
unclassified Actinomyces
Parabacteroides distasonis

Revision editor(s): Aishat, Scholastica

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2024-6-25

Curated date: 2024/06/24

Curator: Scholastica

Revision editor(s): Scholastica

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Infants who are HIV unexposed and uninfected (iHUU) at week 15
Group 1 name Corresponds to the case (exposed) group for case-control studies
Infants who are HIV exposed but uninfected (iHEU) at week 15
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Infants at 15 weeks of age born to mothers from South Africa who have HIV but are not themselves infected with HIV adjusted by mode of feeding

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Confounders controlled for: "mode of feeding" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.mode of feeding

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-6-25

Curated date: 2024/06/24

Curator: Scholastica

Revision editor(s): Scholastica

Source: Table 2

Description: Differentially abundant ASVs (adj P < 0.05) among iHEU (infants who are HIV exposed but uninfected) relative to iHUU (infants who are HIV unexposed and uninfected) at 15 weeks of age in South Africa adjusted by mode of feeding

Abundance in Group 1: increased abundance in Infants who are HIV exposed but uninfected (iHEU) at week 15

NCBI Quality ControlLinks
Bifidobacterium adolescentis
Collinsella aerofaciens
Dorea formicigenerans
Enterococcus faecalis
Enterococcus gilvus
Enterococcus raffinosus
Faecalibacterium prausnitzii
Klebsiella quasipneumoniae
Lactococcus lactis
Streptococcus gallolyticus
Veillonella atypica
unclassified Enterococcus
unclassified Granulicatella
unclassified Staphylococcus
unclassified Clostridium innocuum groupunclassified Clostridium innocuum group

Revision editor(s): Scholastica

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-6-25

Curated date: 2024/06/24

Curator: Scholastica

Revision editor(s): Scholastica

Source: Table 2

Description: Differentially abundant ASVs (adj P < 0.05) among iHEU (infants who are HIV exposed but uninfected) relative to iHUU (infants who are HIV unexposed and uninfected) at 15 weeks of age in South Africa adjusted by mode of feeding

Abundance in Group 1: decreased abundance in Infants who are HIV exposed but uninfected (iHEU) at week 15

NCBI Quality ControlLinks
Bacteroides caccae
Klebsiella michiganensis
Lacticaseibacillus rhamnosus
Lactobacillus gasseri
Megasphaera elsdenii
Segatella copri
[Ruminococcus] torques
unclassified Olsenella
unclassified Prevotella

Revision editor(s): Scholastica

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2024-6-25

Curated date: 2024/06/24

Curator: Scholastica

Revision editor(s): Scholastica

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Infants at 15 weeks of age born to mothers from South Africa who have HIV but are not themselves infected with HIV when adjusted for reported antibiotic (co-trimoxazole) prophylaxis history adjusted by mode of feeding and reported antibiotics history

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
antibiotic exposure, Confounders controlled for: "mode of feeding" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.mode of feeding

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-6-25

Curated date: 2024/06/24

Curator: Scholastica

Revision editor(s): Scholastica

Source: Supplementary Table S2

Description: Differentially abundant ASVs (adj P < 0.05) among iHEU (infants who are HIV exposed but uninfected) relative to iHUU (infants who are HIV unexposed and uninfected) at 15 weeks of age in South Africa adjusted by mode of feeding and reported antibiotics history

Abundance in Group 1: increased abundance in Infants who are HIV exposed but uninfected (iHEU) at week 15

NCBI Quality ControlLinks
Collinsella aerofaciens
Klebsiella quasipneumoniae
Bifidobacterium adolescentis
Streptococcus gallolyticus
Enterococcus gilvus
Lactococcus lactis
Enterococcus raffinosus
unclassified Clostridium innocuum groupunclassified Clostridium innocuum group
Dorea formicigenerans
Corynebacterium propinquum
Faecalibacterium prausnitzii
Leuconostoc lactis
unclassified Granulicatella
Rothia mucilaginosa
Streptococcus salivarius
Streptococcus peroris

Revision editor(s): Scholastica

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-6-25

Curated date: 2024/06/24

Curator: Scholastica

Revision editor(s): Scholastica

Source: Supplementary Table S2

Description: Differentially abundant ASVs (adj P < 0.05) among iHEU (infants who are HIV exposed but uninfected) relative to iHUU (infants who are HIV unexposed and uninfected) at 15 weeks of age in South Africa adjusted by mode of feeding and reported antibiotics history

Abundance in Group 1: decreased abundance in Infants who are HIV exposed but uninfected (iHEU) at week 15

NCBI Quality ControlLinks
Limosilactobacillus vaginalis
Limosilactobacillus fermentum
Parabacteroides distasonis
Lacticaseibacillus rhamnosus
unclassified Veillonella
Enterococcus gilvus
Megasphaera elsdenii
unclassified Olsenella
unclassified Senegalimassilia
Klebsiella michiganensis
Bacteroides caccae
unclassified Prevotella
Veillonella parvula
[Ruminococcus] torques

Revision editor(s): Scholastica