Bifidobacteria support optimal infant vaccine responses

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
Ryan FJ, Clarke M, Lynn MA, Benson SC, McAlister S, Giles LC, Choo JM, Rossouw C, Ng YY, Semchenko EA, Richard A, Leong LEX, Taylor SL, Blake SJ, Mugabushaka JI, Walker M, Wesselingh SL, Licciardi PV, Seib KL, Tumes DJ, Richmond P, Rogers GB, Marshall HS, Lynn DJ
Journal
Nature
Year
2025
Accumulating evidence indicates that antibiotic exposure may lead to impaired vaccine responses1-4; however, the mechanisms underlying this association remain poorly understood. Here we prospectively followed 191 healthy, vaginally born, term infants from birth to 15 months, using a systems vaccinology approach to assess the effects of antibiotic exposure on immune responses to vaccination. Exposure to direct neonatal but not intrapartum antibiotics was associated with significantly lower antibody titres against various polysaccharides in the 13-valent pneumococcal conjugate vaccine and the Haemophilus influenzae type b polyribosylribitol phosphate and diphtheria toxoid antigens in the combined 6-in-1 Infanrix Hexa vaccine at 7 months of age. Blood from infants exposed to neonatal antibiotics had an inflammatory transcriptional profile before vaccination; in addition, faecal metagenomics showed reduced abundance of Bifidobacterium species in these infants at the time of vaccination, which was correlated with reduced vaccine antibody titres 6 months later. In preclinical models, responses to the 13-valent pneumococcal conjugate vaccine were strongly dependent on an intact microbiota but could be restored in germ-free mice by administering a consortium of Bifidobacterium species or a probiotic already widely used in neonatal units. Our data suggest that microbiota-targeted interventions could mitigate the detrimental effects of early-life antibiotics on vaccine immunogenicity.

Experiment 1


Needs review

Curated date: 2025/04/07

Curator: ShadeAkinremi

Revision editor(s): ShadeAkinremi, Chloe, Victoria

Subjects

Location of subjects
Australia
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
Response to antibiotic Response to antibiotic,response to antibiotic
Group 0 name Corresponds to the control (unexposed) group for case-control studies
No Antibiotic (No-ABX) group [Week-1]
Group 1 name Corresponds to the case (exposed) group for case-control studies
Intrapartum Antibiotic (IP-ABX) group [Week-1]
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Infants whose mothers received intrapartum antibiotics (within 28 days before or during delivery) and had no direct infant antibiotic exposure up to 6 weeks of age.
Group 0 sample size Number of subjects in the control (unexposed) group
80
Group 1 sample size Number of subjects in the case (exposed) group
49

Lab analysis

Sequencing type
WMS
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
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
Linear Regression
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)?
No
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Confounders controlled for: "collection day" 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.collection day, sex, formula feeding

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/04/10

Curator: ShadeAkinremi

Revision editor(s): ShadeAkinremi, Victoria

Source: Extented figure 6(g, h, i) And Supplementary Table 11a&b

Description: Differentially abundant microbial species in stool samples collected from IP-ABX infants at week 1 compared to No-ABX infants. Only taxa detected in >5% of samples are considered for differential abundance analysis.

Abundance in Group 1: increased abundance in Intrapartum Antibiotic (IP-ABX) group [Week-1]

NCBI Quality ControlLinks
Atlantibacter hermannii
Citrobacter amalonaticus
Citrobacter freundii
Citrobacter koseri
Citrobacter youngae
Enterobacter
Enterobacter chengduensis
Enterobacter cloacae
Enterobacter hormaechei
Enterobacter ludwigii
Enterococcus raffinosus
Haemophilus
Haemophilus parainfluenzae
Klebsiella aerogenes
Klebsiella pneumoniae
Neisseria subflava
Pantoea septica
Schaalia odontolytica
Streptococcus infantis
Streptococcus peroris
Veillonella sp002959755Veillonella sp002959755
Veillonella sp900550175Veillonella sp900550175
Haemophilus sp900756875Haemophilus sp900756875
Neisseria sp000186165Neisseria sp000186165
Haemophilus sp900755445Haemophilus sp900755445
Haemophilus sp001679485Haemophilus sp001679485
Lancefieldella sp000564995Lancefieldella sp000564995
Haemophilus sp001815355Haemophilus sp001815355

Revision editor(s): ShadeAkinremi, Victoria

Signature 2

Needs review

Curated date: 2025/04/10

Curator: ShadeAkinremi

Revision editor(s): ShadeAkinremi, Victoria

Source: Extented figure 6(g, h, i) And Supplementary Table 11a&b

Description: Differentially abundant microbial species in stool samples collected from IP-ABX infants at week 1 compared to No-ABX infants. Only taxa detected in >5% of samples are considered for differential abundance analysis.

Abundance in Group 1: decreased abundance in Intrapartum Antibiotic (IP-ABX) group [Week-1]

NCBI Quality ControlLinks
Bacteroides
Bifidobacterium
Bifidobacterium breve
Bifidobacterium catenulatum
Bifidobacterium longum subsp. infantis
Bifidobacterium pseudocatenulatum
Parabacteroides
Phocaeicola
Bifidobacterium sp002742445Bifidobacterium sp002742445

Revision editor(s): ShadeAkinremi, Victoria

Experiment 2


Needs review

Curated date: 2025/04/14

Curator: ShadeAkinremi

Revision editor(s): ShadeAkinremi, Victoria

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Neonatal Antibotic (Neo-ABX) group [Week-1]
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Infants who received at least 48 h of antibiotic treatment in the neonatal period (the first 28 days after birth), with or without maternal antibiotic exposure.
Group 1 sample size Number of subjects in the case (exposed) group
32

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/04/14

Curator: ShadeAkinremi

Revision editor(s): ShadeAkinremi, Victoria

Source: Supplementary Table 11b

Description: Differentially abundant microbial species in stool samples collected from Neo-ABX infants at week 1 compared to No-ABX infants. Only taxa detected in >5% of samples are considered for differential abundance analysis.

Abundance in Group 1: increased abundance in Neonatal Antibotic (Neo-ABX) group [Week-1]

NCBI Quality ControlLinks
Citrobacter
Enterobacter
Enterococcus
Escherichia
Haemophilus
Klebsiella
Staphylococcus

Revision editor(s): ShadeAkinremi, Victoria

Signature 2

Needs review

Curated date: 2025/04/15

Curator: ShadeAkinremi

Revision editor(s): ShadeAkinremi, Victoria

Source: Supplementary Table 11a

Description: Differentially abundant microbial species in stool samples collected from Neo-ABX infants at week 1 compared to No-ABX infants. Only taxa detected in >5% of samples are considered for differential abundance analysis.

Abundance in Group 1: decreased abundance in Neonatal Antibotic (Neo-ABX) group [Week-1]

NCBI Quality ControlLinks
Bifidobacterium adolescentis
Bifidobacterium angulatum
Bifidobacterium pseudocatenulatum
Collinsella aerofaciens
Collinsella sp003458415Collinsella sp003458415
Collinsella sp002232035Collinsella sp002232035
Streptococcus sp001556435Streptococcus sp001556435

Revision editor(s): ShadeAkinremi, Victoria

Experiment 3


Needs review

Curated date: 2025/04/15

Curator: ShadeAkinremi

Revision editor(s): ShadeAkinremi, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
No Antibiotic (No-ABX) group [Week-6]
Group 1 name Corresponds to the case (exposed) group for case-control studies
Neonatal Antibotic (Neo-ABX) group [Week-6]

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

Signature 1

Needs review

Curated date: 2025/04/15

Curator: ShadeAkinremi

Revision editor(s): ShadeAkinremi, Victoria

Source: Extented figure 6(j, k, l) And Supplementary Table 11a&b

Description: Differentially abundant microbial species in stool samples collected from Neo-ABX infants at week 6 compared to No-ABX infants. Only taxa detected in >5% of samples are considered for differential abundance analysis.

Abundance in Group 1: decreased abundance in Neonatal Antibotic (Neo-ABX) group [Week-6]

NCBI Quality ControlLinks
Bifidobacterium
Bifidobacterium adolescentis
Bifidobacterium angulatum
Bifidobacterium bifidum
Bifidobacterium breve
Bifidobacterium pseudocatenulatum
Collinsella aerofaciens
Collinsella sp002232035Collinsella sp002232035
Collinsella sp900540095Collinsella sp900540095
Bifidobacterium sp002742445Bifidobacterium sp002742445

Revision editor(s): ShadeAkinremi, Victoria