Evolution of the Gut Microbiome in HIV-Exposed Uninfected and Unexposed Infants during the First Year of Life

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Jackson CL, Frank DN, Robertson CE, Ir D, Kofonow JM, Montlha MP, Mutsaerts EAML, Nunes MC, Madhi SA, Ghosh D, Weinberg A
Journal
mBio
Year
2022
HIV-exposed uninfected infants (HEU) have abnormal immunologic functions and increased infectious morbidity in the first 6 months of life, which gradually decreases thereafter. The mechanisms underlying HEU immune dysfunctions are unknown. We hypothesized that unique characteristics of the HEU gut microbiota associated with maternal HIV status may underlie the HEU immunologic dysfunctions. We characterized the infant gut, maternal gut, and breast milk microbiomes of mother-infant pairs, including 123 with HEU and 117 with HIV-uninfected infants (HUU), from South Africa. Pan-bacterial 16S rRNA gene sequencing was performed on (i) infant stool at 6, 28, and 62 weeks; (ii) maternal stool at delivery and 62 weeks; and (iii) breast milk at 6 weeks. Infant gut alpha and beta diversities were similar between groups. Microbial composition significantly differed, including 12 genera, 5 families and 1 phylum at 6 weeks; 12 genera and 2 families at 28 weeks; and 2 genera and 2 families at 62 weeks of life. Maternal gut microbiomes significantly differed in beta diversity and microbial composition, and breast milk microbiomes differed in microbial composition only. Infant gut microbiotas extensively overlapped with maternal gut and minimally with breast milk microbiotas. Nevertheless, exclusively breastfed HEU and HUU had less divergent microbiomes than nonexclusively breastfed infants. Feeding pattern and maternal gut microbiome imprint the HEU gut microbiome. Compared to HUU, the HEU gut microbiome prominently differs in early infancy, including increased abundance of taxa previously observed to be present in excess in adults with HIV. The HEU and HUU gut microbiome compositions converge over time, mirroring the kinetics of HEU infectious morbidity risk. IMPORTANCE HIV-exposed uninfected infants (HEU) are highly vulnerable to infections in the first 6 months of life, and this vulnerability decreases to the age of 24 months. Because the microbiome plays a critical role in the education of the infant immune system, which protects them against infections, we characterized the gut microbiomes of HEU and HIV-unexposed infants (HUU) in the first year of life. The HEU and HUU gut microbiomes showed prominent differences at 6 and 28 weeks of life but converged at 62 weeks of life, mirroring the time course of the HEU excess infectious morbidity and suggesting a potential association between the infant gut microbiome structure and susceptibility to infections. Infant gut microbiotas extensively overlapped with maternal gut and minimally with breast milk microbiotas. Moreover, exclusively breastfed HEU and HUU had less divergent microbiomes at 6 and 28 weeks than nonexclusively breastfed HEU and HUU. The factors that affect the HEU gut microbiome, maternal gut microbiome and exclusive breastfeeding, may be targeted by interventions.

Experiment 1


Needs review

Curated date: 2023/03/09

Curator: BLESSING123

Revision editor(s): BLESSING123

Subjects

Location of subjects
South Africa
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
HIV mother to child transmission HIV MTCT,HIV mother to child transmission
Group 0 name Corresponds to the control (unexposed) group for case-control studies
HIV- unexposed uninfected controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
HIV-exposed uninfected
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Infants exposed to HIV from their birth mothers but uninfected
Group 0 sample size Number of subjects in the control (unexposed) group
78
Group 1 sample size Number of subjects in the case (exposed) group
76
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Infants who had been on antibiotics or HIV-exposed uninfected infants that had been on Bactrim after 6 weeks of birth were excluded.

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
DESeq2
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
Matched on Factors on which subjects have been matched on in a case-control study
age, sex
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
antibiotic exposure


Signature 1

Needs review

Curated date: 2023/03/09

Curator: BLESSING123

Revision editor(s): BLESSING123

Source: Figure 2d

Description: Increased abundance in HIV-exposed uninfected infants

Abundance in Group 1: increased abundance in HIV-exposed uninfected

NCBI Links
Eggerthella
Barnesiella
Odoribacter
Blautia
Sneathia
unclassified Bacillota
unclassified Oscillospiraceae

Revision editor(s): BLESSING123

Signature 2

Needs review

Curated date: 2023/03/09

Curator: BLESSING123

Revision editor(s): BLESSING123

Source: Figure 2d

Description: Decreased abundance in HIV-exposed uninfected infants

Abundance in Group 1: decreased abundance in HIV-exposed uninfected

NCBI Links
Catenibacterium
Megamonas
Enterobacter
Candidatus Saccharibacteria genomosp. TM7-H1
unclassified Bacteroidota

Revision editor(s): BLESSING123

Experiment 2


Needs review

Curated date: 2023/03/09

Curator: BLESSING123

Revision editor(s): BLESSING123

Subjects

Location of subjects
South Africa
Host species Species from which microbiome was sampled (if applicable)
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
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
HIV mother to child transmission HIV MTCT,HIV mother to child transmission
Group 0 name Corresponds to the control (unexposed) group for case-control studies
HIV- unexposed uninfected controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
HIV-exposed uninfected
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Infants exposed to HIV from their birth mothers but uninfected
Group 0 sample size Number of subjects in the control (unexposed) group
74
Group 1 sample size Number of subjects in the case (exposed) group
71
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Infants who had been on antibiotics or HIV-exposed uninfected infants that had not been on Bactrim after 28 weeks of birth were excluded

Lab analysis

Sequencing type
16S
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
DESeq2
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
Matched on Factors on which subjects have been matched on in a case-control study
age, sex
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
antibiotic exposure

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Richness Number of species
increased

Signature 1

Needs review

Curated date: 2023/03/09

Curator: BLESSING123

Revision editor(s): BLESSING123

Source: Figure 2d

Description: Increased abundance in HIV-exposed uninfected infants

Abundance in Group 1: increased abundance in HIV-exposed uninfected

NCBI Links
Candidatus Epulonipiscium
Klebsiella
Lactococcus
Megamonas
Parasutterella
unclassified Eubacteriales

Revision editor(s): BLESSING123

Signature 2

Needs review

Curated date: 2023/03/09

Curator: BLESSING123

Revision editor(s): BLESSING123

Source: Figure 2d

Description: Decreased abundance in HIV-exposed uninfected infants

Abundance in Group 1: decreased abundance in HIV-exposed uninfected

NCBI Links
Atopobium
Gardnerella
Gemella
Mobiluncus
Parvimonas
Sneathia

Revision editor(s): BLESSING123

Experiment 3


Needs review

Curated date: 2023/03/09

Curator: BLESSING123

Revision editor(s): BLESSING123

Subjects

Location of subjects
South Africa
Host species Species from which microbiome was sampled (if applicable)
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
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
HIV mother to child transmission HIV MTCT,HIV mother to child transmission
Group 0 name Corresponds to the control (unexposed) group for case-control studies
HIV- unexposed uninfected controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
HIV-exposed uninfected
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Infants exposed to HIV from their birth mothers but uninfected
Group 0 sample size Number of subjects in the control (unexposed) group
70
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)
Infants who had been on antibiotics or HIV-exposed uninfected infants that had not been on Bactrim after 62 weeks of birth were excluded

Lab analysis

Sequencing type
16S
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
DESeq2
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
Matched on Factors on which subjects have been matched on in a case-control study
age, sex
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
antibiotic exposure

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Richness Number of species
unchanged

Signature 1

Needs review

Curated date: 2023/03/09

Curator: BLESSING123

Revision editor(s): BLESSING123

Source: Figure 2d

Description: Decreased abundance in HIV-exposed uninfected infants

Abundance in Group 1: decreased abundance in HIV-exposed uninfected

NCBI Links
Proteus
unclassified Coriobacteriaceae

Revision editor(s): BLESSING123

Experiment 4


Needs review

Curated date: 2023/03/10

Curator: BLESSING123

Revision editor(s): BLESSING123

Subjects

Location of subjects
South Africa
Host species Species from which microbiome was sampled (if applicable)
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
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
HIV mother to child transmission HIV MTCT,HIV mother to child transmission
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
HIV-infected mothers
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Mothers infected with HIV
Group 0 sample size Number of subjects in the control (unexposed) group
110
Group 1 sample size Number of subjects in the case (exposed) group
119
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Mothers on antibiotics as at the time of delivery

Lab analysis

Sequencing type
16S
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
PERMANOVA
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
Matched on Factors on which subjects have been matched on in a case-control study
sex


Signature 1

Needs review

Curated date: 2023/03/10

Curator: BLESSING123

Revision editor(s): BLESSING123

Source: Figure 3F

Description:

Abundance in Group 1: increased abundance in HIV-infected mothers

NCBI Links
unclassified Corynebacteriaceae
Corynebacterium
Bacteroides
Acidaminococcus
Anaerococcus
unclassified Bacilli
Blautia
unclassified Erysipelotrichaceae
Flavonifractor
Granulicatella
unclassified Lachnospiraceae
Staphylococcus
unclassified Fusobacteriales
Fusobacterium
Bilophila
unclassified Burkholderiales
Klebsiella
Sutterella
Mycoplasma

Revision editor(s): BLESSING123

Signature 2

Needs review

Curated date: 2023/03/13

Curator: BLESSING123

Revision editor(s): BLESSING123

Source: Figure 3F

Description:

Abundance in Group 1: decreased abundance in HIV-infected mothers

NCBI Links
Elusimicrobium
Asteroleplasma
unclassified Clostridiales Family XVII.
Faecalibacterium
Haemophilus

Revision editor(s): BLESSING123

Experiment 5


Needs review

Curated date: 2023/03/10

Curator: BLESSING123

Revision editor(s): BLESSING123

Subjects

Location of subjects
South Africa
Host species Species from which microbiome was sampled (if applicable)
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
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
HIV mother to child transmission HIV MTCT,HIV mother to child transmission
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
HIV-infected mothers
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Mothers infected with HIV
Group 0 sample size Number of subjects in the control (unexposed) group
65
Group 1 sample size Number of subjects in the case (exposed) group
71

Lab analysis

Sequencing type
16S
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
PERMANOVA
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
Matched on Factors on which subjects have been matched on in a case-control study
age, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Richness Number of species
unchanged

Signature 1

Needs review

Curated date: 2023/03/13

Curator: BLESSING123

Revision editor(s): BLESSING123

Source: Figure 3F

Description:

Abundance in Group 1: increased abundance in HIV-infected mothers

NCBI Links
Collinsella
Parabacteroides
Acidaminococcus
Anaerostipes
Blautia
Dorea
Faecalibacterium
Flavonifractor
Megamonas
Subdoligranulum
Thalassospira
unclassified Synergistaceae

Revision editor(s): BLESSING123

Signature 2

Needs review

Curated date: 2023/03/13

Curator: BLESSING123

Revision editor(s): BLESSING123

Source: Figure 3F

Description:

Abundance in Group 1: decreased abundance in HIV-infected mothers

NCBI Links
unclassified Corynebacteriaceae
Prevotella
Elusimicrobium
Gemella
Staphylococcus
Veillonella
unclassified Veillonellaceae
Acinetobacter

Revision editor(s): BLESSING123

Experiment 6


Needs review

Curated date: 2023/03/10

Curator: BLESSING123

Revision editor(s): BLESSING123

Subjects

Location of subjects
South Africa
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Milk Mammary gland milk,Milk
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
HIV mother to child transmission HIV MTCT,HIV mother to child transmission
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
HIV-infected mothers
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Mothers 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
88

Lab analysis

Sequencing type
16S
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
PERMANOVA
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
Matched on Factors on which subjects have been matched on in a case-control study
sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Richness Number of species
unchanged

Signature 1

Needs review

Curated date: 2023/03/13

Curator: BLESSING123

Revision editor(s): BLESSING123

Source: Figure 4F

Description:

Abundance in Group 1: decreased abundance in HIV-infected mothers

NCBI Links
unclassified Peptostreptococcaceae

Revision editor(s): BLESSING123

Signature 2

Needs review

Curated date: 2023/03/13

Curator: BLESSING123

Revision editor(s): BLESSING123

Source: Figure 4F

Description:

Abundance in Group 1: increased abundance in HIV-infected mothers

NCBI Links
Anaerococcus
Arthrobacter
Atopobium
Bacillus
Blastococcus
Brevibacterium
Chryseobacterium
Corynebacterium
Enterococcus
Exiguobacterium
Faecalibacterium
Finegoldia
Gardnerella
Hymenobacter
Micrococcus
Nocardioides
Prevotella
Propionibacterium
Pseudonocardia
Rubrobacter
unclassified Acidimicrobiales
unclassified Bacillales
unclassified Carnobacteriaceae
unclassified Chitinophagaceae
unclassified Corynebacteriales
unclassified Geodermatophilaceae
unclassified Microbacteriaceae
unclassified Micromonosporaceae
unclassified Nocardiaceae
unclassified Lachnospiraceae
unclassified Lactobacillales
Peptoniphilus
Pseudobutyrivibrio
Lactococcus
unclassified Oscillospiraceae
Staphylococcus
unclassified Enterobacteriaceae
Herbaspirillum
Massilia
Methylobacterium
Microvirga
Moraxella
Neisseria
unclassified Neisseriaceae
unclassified Oxalobacteraceae
Rubellimicrobium
unclassified Sphingomonadales
unclassified Xanthomonadaceae

Revision editor(s): BLESSING123