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
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
Keywords:
HIV, HIV-exposed uninfected infants, breast milk microbiome, gut microbiome, human immunodeficiency virus, pregnant women with HIV
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
Reviewed Marked as Reviewed by Atrayees on 2023-6-2
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
- HIV mother to child transmission HIV MTCT,HIV mother to child transmission,hIV mother to child transmission
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- HIV-unexposed infants (HUU) at 6 weeks
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HIV-exposed uninfected infants (HEU) at 6 weeks
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- In utero-HIV exposed uninfected infants (HEU) at 6 weeks
- 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 that did not pass the sequence quality control, those on antibiotics, and HEU infants on Bactrim after 6 weeks of birth.
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).
- raw counts
- 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
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
Reviewed Marked as Reviewed by Atrayees on 2023-6-2
Source: Figure 2d
Description: Genera with significantly different relative abundances between HEU and HUU at 6-weeks.
Abundance in Group 1: increased abundance in HIV-exposed uninfected infants (HEU) at 6 weeks
| NCBI | Quality Control | Links |
|---|---|---|
| Barnesiella | ||
| Blautia | ||
| Eggerthella | ||
| Odoribacter | ||
| Sneathia | ||
| unclassified Bacillota | ||
| unclassified Oscillospiraceae |
Revision editor(s): BLESSING123
Signature 2
Reviewed Marked as Reviewed by Atrayees on 2023-6-2
Source: Figure 2d
Description: Genera with significantly different relative abundances between HEU and HUU at 6-weeks.
Abundance in Group 1: decreased abundance in HIV-exposed uninfected infants (HEU) at 6 weeks
| NCBI | Quality Control | Links |
|---|---|---|
| Candidatus Saccharibacteria genomosp. TM7-H1 | ||
| Catenibacterium | ||
| Enterobacter | ||
| Megamonas | ||
| unclassified Bacteroidota |
Revision editor(s): BLESSING123
Experiment 2
Reviewed Marked as Reviewed by Atrayees on 2023-6-2
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- HIV-unexposed infants (HUU) at 28 weeks
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HIV-exposed uninfected infants (HEU) at 28 weeks
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- In utero-HIV exposed uninfected infants (HEU)
- 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)
- Unexposed Infants who had been on antibiotics and HIV-exposed uninfected infants that had not been on Bactrim after 28 weeks of birth were excluded
Lab analysis
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- 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
Reviewed Marked as Reviewed by Atrayees on 2023-6-2
Source: Figure 2d
Description: Genera with significantly different relative abundances between HEU and HUU at 28-weeks.
Abundance in Group 1: increased abundance in HIV-exposed uninfected infants (HEU) at 28 weeks
| NCBI | Quality Control | Links |
|---|---|---|
| Candidatus Epulonipiscium sp. | ||
| Klebsiella | ||
| Lactococcus | ||
| Megamonas | ||
| Parasutterella | ||
| unclassified Eubacteriales |
Revision editor(s): BLESSING123
Signature 2
Reviewed Marked as Reviewed by Atrayees on 2023-6-2
Source: Figure 2d
Description: Genera with significantly different relative abundances between HEU and HUU at 28-weeks.
Abundance in Group 1: decreased abundance in HIV-exposed uninfected infants (HEU) at 28 weeks
| NCBI | Quality Control | Links |
|---|---|---|
| Atopobium | ||
| Gardnerella | ||
| Gemella | ||
| Mobiluncus | ||
| Parvimonas | ||
| Sneathia |
Revision editor(s): BLESSING123
Experiment 3
Reviewed Marked as Reviewed by Atrayees on 2023-6-2
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- HIV-unexposed infants (HUU) at 62 weeks
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HIV-exposed uninfected infants (HEU) at 62 weeks
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- In utero-HIV exposed uninfected infants (HEU) at 62 weeks
- 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 and HIV-exposed uninfected infants that had not been on Bactrim after 62 weeks of birth were excluded
Lab analysis
Statistical Analysis
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
Reviewed Marked as Reviewed by Atrayees on 2023-6-2
Source: Figure 2d
Description: Genera with significantly different relative abundances between HEU and HUU at the indicated time points (FDR P < 0.05). 62 weeks
Abundance in Group 1: decreased abundance in HIV-exposed uninfected infants (HEU) at 62 weeks
| NCBI | Quality Control | Links |
|---|---|---|
| Proteus | ||
| unclassified Coriobacteriaceae |
Revision editor(s): BLESSING123
Experiment 4
Reviewed Marked as Reviewed by Atrayees on 2023-6-2
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy controls at delivery
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HIV-infected mothers at delivery
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Mothers infected with HIV at delivery time point
- 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
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- raw counts
- Matched on Factors on which subjects have been matched on in a case-control study
- sex
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Not specified
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
Reviewed Marked as Reviewed by Atrayees on 2023-6-2
Source: Figure 3F
Description: Genera with significantly different relative abundances between mothers with and without HIV at the indicated time points (FDR P < 0.05). Delivery
Abundance in Group 1: increased abundance in HIV-infected mothers at delivery
Revision editor(s): BLESSING123, Folakunmi
Signature 2
Reviewed Marked as Reviewed by Atrayees on 2023-6-2
Source: Figure 3F
Description: Genera with significantly different relative abundances between mothers with and without HIV at the indicated time points (FDR P < 0.05). Delivery
Abundance in Group 1: decreased abundance in HIV-infected mothers at delivery
| NCBI | Quality Control | Links |
|---|---|---|
| Asteroleplasma | ||
| Elusimicrobium | ||
| Faecalibacterium | ||
| Haemophilus | ||
| unclassified Clostridiales Family XVII. |
Revision editor(s): BLESSING123
Experiment 5
Reviewed Marked as Reviewed by Atrayees on 2023-6-2
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy controls at 62 weeks
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HIV-infected mothers at 62 weeks
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Mothers infected with HIV at 62 weeks time point
- 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
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Not specified
Lab analysis
Statistical Analysis
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
Reviewed Marked as Reviewed by Folakunmi on 2024-2-9
Source: Figure 3F
Description: Genera with significantly different relative abundances between mothers with and without HIV at the indicated time points (FDR P < 0.05). 62 weeks
Abundance in Group 1: increased abundance in HIV-infected mothers at 62 weeks
Revision editor(s): BLESSING123, Folakunmi
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-2-9
Source: Figure 3F
Description: Genera with significantly different relative abundances between mothers with and without HIV at the indicated time points (FDR P < 0.05). 62 weeks
Abundance in Group 1: decreased abundance in HIV-infected mothers at 62 weeks
| NCBI | Quality Control | Links |
|---|---|---|
| Acinetobacter | ||
| Elusimicrobium | ||
| Gemella | ||
| Prevotella | ||
| Staphylococcus | ||
| Veillonella | ||
| unclassified Corynebacteriaceae | ||
| unclassified Veillonellaceae |
Revision editor(s): BLESSING123
Experiment 6
Reviewed Marked as Reviewed by Folakunmi on 2024-2-9
Differences from previous experiment shown
Subjects
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Milk Mammary gland milk,Milk,milk
- 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
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
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
Reviewed Marked as Reviewed by Folakunmi on 2024-2-9
Source: Figure 4F
Description: Genera with significantly different abundances in mothers with and without HIV (FDR P < 0.05).
Abundance in Group 1: decreased abundance in HIV-infected mothers
| NCBI | Quality Control | Links |
|---|---|---|
| unclassified Peptostreptococcaceae |
Revision editor(s): BLESSING123
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-2-9
Source: Figure 4F
Description: Genera with significantly different abundances in mothers with and without HIV (FDR P < 0.05).
Abundance in Group 1: increased abundance in HIV-infected mothers
Revision editor(s): BLESSING123
Experiment 7
Reviewed Marked as Reviewed by Folakunmi on 2024-2-9
Differences from previous experiment shown
Subjects
- 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
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Exclusively breastfed HIV-unexposed infants (HUU) at 28 weeks
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Exclusively breastfed HIV-exposed uninfected infants (HEU) at 28 weeks
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Exclusively breastfed In utero-HIV exposed uninfected infants (HEU) at 28 weeks
- Group 0 sample size Number of subjects in the control (unexposed) group
- 40
- Group 1 sample size Number of subjects in the case (exposed) group
- 52
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Unexposed Infants who had been on antibiotics and HIV-exposed uninfected infants that had not been on Bactrim after 28 weeks of birth were excluded
Lab analysis
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- raw counts
- Matched on Factors on which subjects have been matched on in a case-control study
- Not specified
- 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
Reviewed Marked as Reviewed by Folakunmi on 2024-2-9
Source: Figure 2e
Description: Genera with significantly different relative abundances between HEU and HUU exclusively (Excl.) breastfed at 28 weeks of life
Abundance in Group 1: increased abundance in Exclusively breastfed HIV-exposed uninfected infants (HEU) at 28 weeks
| NCBI | Quality Control | Links |
|---|---|---|
| Candidatus Epulonipiscium |
Revision editor(s): Folakunmi
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-2-9
Source: Figure 2e
Description: Genera with significantly different relative abundances between HEU and HUU exclusively (Excl.) breastfed at 28 weeks of life
Abundance in Group 1: decreased abundance in Exclusively breastfed HIV-exposed uninfected infants (HEU) at 28 weeks
| NCBI | Quality Control | Links |
|---|---|---|
| Sneathia |
Revision editor(s): Folakunmi
Experiment 8
Reviewed Marked as Reviewed by Folakunmi on 2024-2-9
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Not exclusively breastfed HIV-unexposed infants (HUU) at 28 weeks
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Not exclusively breastfed HIV-exposed uninfected infants (HEU) at 28 weeks
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Not exclusively breastfed (formula feeding) In utero-HIV exposed uninfected infants (HEU) at 28 weeks
- Group 0 sample size Number of subjects in the control (unexposed) group
- 9
- Group 1 sample size Number of subjects in the case (exposed) group
- 19
Lab analysis
Statistical Analysis
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
Reviewed Marked as Reviewed by Folakunmi on 2024-2-9
Source: Figure 2e
Description: Genera with significantly different relative abundances between HEU and HUU not exclusively (Excl.) breastfed at 28 weeks of lif
Abundance in Group 1: increased abundance in Not exclusively breastfed HIV-exposed uninfected infants (HEU) at 28 weeks
| NCBI | Quality Control | Links |
|---|---|---|
| Candidatus Epulonipiscium | ||
| unclassified_E01-9C-26unclassified_E01-9C-26 | ||
| Klebsiella | ||
| Pasteurella |
Revision editor(s): Folakunmi
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-2-9
Source: figure 2e
Description: Genera with significantly different relative abundances between HEU and HUU not exclusively (Excl.) breastfed at 28 weeks of life
Abundance in Group 1: decreased abundance in Not exclusively breastfed HIV-exposed uninfected infants (HEU) at 28 weeks
| NCBI | Quality Control | Links |
|---|---|---|
| Gardnerella | ||
| Mobiluncus | ||
| Alistipes | ||
| Catenibacterium | ||
| Dialister | ||
| Finegoldia | ||
| Gemella | ||
| Peptococcus | ||
| Peptostreptococcus | ||
| Solobacterium | ||
| Sneathia |
Revision editor(s): Folakunmi
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