Feeding-Related Gut Microbial Composition Associates With Peripheral T-Cell Activation and Mucosal Gene Expression in African Infants

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Reviewed Marked as Reviewed by Svetlana up on 2024-12-11
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Wood LF, Brown BP, Lennard K, Karaoz U, Havyarimana E, Passmore JS, Hesseling AC, Edlefsen PT, Kuhn L, Mulder N, Brodie EL, Sodora DL, Jaspan HB
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Year
2018
BACKGROUND: Exclusive breastfeeding reduces the rate of postnatal human immunodeficiency virus (HIV) transmission compared to nonexclusive breastfeeding; however, the mechanisms of this protection are unknown. Our study aimed to interrogate the mechanisms underlying the protective effect of exclusive breastfeeding. METHODS: We performed a prospective, longitudinal study of infants from a high-HIV-prevalence, low-income setting in South Africa. We evaluated the role of any non-breast milk feeds, excluding prescribed medicines on stool microbial communities via 16S rRNA gene sequencing, peripheral T-cell activation via flow cytometry, and buccal mucosal gene expression via quantitative polymerase chain reaction assay. RESULTS: A total of 155 infants were recruited at birth with mean gestational age of 38.9 weeks and mean birth weight of 3.2 kg. All infants were exclusively breastfed (EBF) at birth, but only 43.5% and 20% remained EBF at 6 or 14 weeks of age, respectively. We observed lower stool microbial diversity and distinct microbial composition in exclusively breastfed infants. These microbial communities, and the relative abundance of key taxa, were correlated with peripheral CD4+ T-cell activation, which was lower in EBF infants. In the oral mucosa, gene expression of chemokine and chemokine receptors involved in recruitment of HIV target cells to tissues, as well as epithelial cytoskeletal proteins, was lower in EBF infants. CONCLUSIONS: These data suggest that nonexclusive breastfeeding alters the gut microbiota, increasing T-cell activation and, potentially, mucosal recruitment of HIV target cells. Study findings highlight a biologically plausible mechanistic explanation for the reduced postnatal HIV transmission observed in EBF infants.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2024-12-11

Curated date: 2024/10/20

Curator: Adwan

Revision editor(s): Adwan, Tosin

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
Non-exclusively breastfed (NEBF) infants at 6 weeks
Group 1 name Corresponds to the case (exposed) group for case-control studies
Exclusively breastfed (EBF) infants at 6 weeks.
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
EBF infants defined as infants fed breast milk only (except for prescribed medicine) from birth to the study visit(6 weeks).
Group 0 sample size Number of subjects in the control (unexposed) group
55
Group 1 sample size Number of subjects in the case (exposed) group
44

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
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

Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-11

Curated date: 2024/10/20

Curator: Adwan

Revision editor(s): Adwan, Tosin

Source: Text: Gut Microbiota Is Altered by Feeding Modality- At 6 weeks, EBF infants had lower relative abundance of Streptococcus luteciae and supplementary Figure 2

Description: Specific taxa differentially abundant in (exclusively breastfed) EBF versus (non-exclusively breastfed) NEBF infants at 6 Weeks. This study represents the gut microbial composition changes observed in non-exclusively breastfed (NEBF) infants compared to exclusively breastfed (EBF) infants.

Abundance in Group 1: decreased abundance in Exclusively breastfed (EBF) infants at 6 weeks.

NCBI Quality ControlLinks
Streptococcus lutetiensis

Revision editor(s): Adwan, Tosin

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2024-12-11

Curated date: 2024/10/20

Curator: Adwan

Revision editor(s): Adwan, Tosin

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Non-exclusively breastfed (NEBF) infants at 14 weeks.
Group 1 name Corresponds to the case (exposed) group for case-control studies
Exclusively breastfed (EBF) infants at 14 weeks.
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
EBF infants defined as infants fed breast milk only (except for prescribed medicine) from birth to the study visit(14 weeks).
Group 0 sample size Number of subjects in the control (unexposed) group
67
Group 1 sample size Number of subjects in the case (exposed) group
17

Lab analysis

Statistical Analysis

Alpha Diversity

Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-11

Curated date: 2024/10/22

Curator: Tosin

Revision editor(s): Tosin

Source: Text: Gut Microbiota Is Altered by Feeding Modality- (At 14 weeks, EBF infants had higher relative abundance of Streptococcus lactarius, as well as Actinomyces and Atopobium) and Supplementary Figure 2.

Description: Specific taxa differentially abundant in (exclusively breastfed) EBF versus (non-exclusively breastfed) NEBF infants at 14 Weeks. This study represents the gut microbial composition changes observed in non-exclusively breastfed (NEBF) infants compared to exclusively breastfed (EBF) infants.

Abundance in Group 1: increased abundance in Exclusively breastfed (EBF) infants at 14 weeks.

NCBI Quality ControlLinks
Actinomyces
Atopobium
Streptococcus lactarius

Revision editor(s): Tosin

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-11

Curated date: 2024/10/22

Curator: Tosin

Revision editor(s): Tosin

Source: Text: Gut Microbiota Is Altered by Feeding Modality- At 14 weeks, EBF infants had lower relative abundance of two Bacteroides OTUs and supplementary Figure 2.

Description: Specific taxa differentially abundant in (exclusively breastfed) EBF versus (non-exclusively breastfed) NEBF infants at 14 Weeks. This study represents the gut microbial composition changes observed in non-exclusively breastfed (NEBF) infants compared to exclusively breastfed (EBF) infants.

Abundance in Group 1: decreased abundance in Exclusively breastfed (EBF) infants at 14 weeks.

NCBI Quality ControlLinks
Bacteroides

Revision editor(s): Tosin

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2024-12-11

Curated date: 2024/10/22

Curator: Tosin

Revision editor(s): Tosin

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Cell activation Cell activation,cell activation
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Infants with Low HL-ADR (Human Leukocyte Antigen - DR isotype) expression on CD4 + T-cell
Group 1 name Corresponds to the case (exposed) group for case-control studies
Infants with High HL-ADR (Human Leukocyte Antigen - DR isotype) expression on CD4 + T-cell
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Infants with high CD4+HLA-DR+ T-cell frequency
Group 0 sample size Number of subjects in the control (unexposed) group
Not specified
Group 1 sample size Number of subjects in the case (exposed) group
Not specified

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age


Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-11

Curated date: 2024/10/24

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 4B

Description: Gut microbial composition partially explains peripheral blood CD4+ T-cell activation. Significantly differentially abundant OTUs merged at the lowest taxonomic level in infants with high HLA-DR expression vs those with low HLA-DR expression, as computed by DeSeq2.

Abundance in Group 1: increased abundance in Infants with High HL-ADR (Human Leukocyte Antigen - DR isotype) expression on CD4 + T-cell

NCBI Quality ControlLinks
Akkermansia muciniphila

Revision editor(s): Tosin

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-11

Curated date: 2024/10/24

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 4B

Description: Gut microbial composition partially explains peripheral blood CD4+ T-cell activation. Significantly differentially abundant OTUs merged at the lowest taxonomic level in infants with high HLA-DR expression vs those with low HLA-DR expression, as computed by DeSeq2.

Abundance in Group 1: decreased abundance in Infants with High HL-ADR (Human Leukocyte Antigen - DR isotype) expression on CD4 + T-cell

NCBI Quality ControlLinks
Streptococcus
Bifidobacterium bifidum
Streptococcus lactarius
Gemellaceae
Staphylococcus
Pantoea agglomerans

Revision editor(s): Tosin