Evolution of the Gut Microbiome in HIV-Exposed Uninfected and Unexposed Infants during the First Year of Life
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
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.
Statistical test
DESeq2
Statistical test
DESeq2
Statistical test
DESeq2
Statistical test
PERMANOVA
Statistical test
PERMANOVA
Statistical test
PERMANOVA
Experiment 1
Needs review
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
- 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
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
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
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
- 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
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
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
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
- 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
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
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
- 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
Source: Figure 3F
Description:
Abundance in Group 1: increased abundance in HIV-infected mothers
Revision editor(s): BLESSING123
Signature 2
Needs review
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
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
- 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
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
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
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
- 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
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
Source: Figure 4F
Description:
Abundance in Group 1: increased abundance in HIV-infected mothers
Revision editor(s): BLESSING123
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