Specific class of intrapartum antibiotics relates to maturation of the infant gut microbiota: a prospective cohort study

Study information

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study design

prospective cohort

Citation

PMID PubMed identifier for scientific articles.

31006170

DOI Digital object identifier for electronic documents.

10.1111/1471-0528.15799

URI Uniform resource identifier for web resources.

Authors

Coker MO, Hoen AG, Dade E, Lundgren S, Li Z, Wong AD, Zens MS, Palys TJ, Morrison HG, Sogin ML, Baker ER, Karagas MR, Madan JC

Journal

BJOG : an international journal of obstetrics and gynaecology

Year

2020

OBJECTIVE: To evaluate the potential impact of intrapartum antibiotics, and their specific classes, on the infant gut microbiota in the first year of life. DESIGN: Prospective study of infants in the New Hampshire Birth Cohort Study (NHBCS). SETTINGS: Rural New Hampshire, USA. POPULATION OR SAMPLE: Two hundred and sixty-six full-term infants from the NHBCS. METHODS: Intrapartum antibiotic use during labour and delivery was abstracted from medical records. Faecal samples collected at 6 weeks and 1 year of age were characterised by 16S rRNA sequencing, and metagenomics analysis in a subset of samples. EXPOSURES: Maternal exposure to antibiotics during labour and delivery. MAIN OUTCOME MEASURE: Taxonomic and functional profiles of faecal samples. RESULTS: Infant exposure to intrapartum antibiotics, particularly to two or more antibiotic classes, was independently associated with lower microbial diversity scores as well as a unique bacterial community at 6 weeks (GUnifrac, P = 0.02). At 1 year, infants in the penicillin-only group had significantly lower α diversity scores than infants not exposed to intrapartum antibiotics. Within the first year of life, intrapartum exposure to penicillins was related to a significantly lower increase in several taxa including Bacteroides, use of cephalosporins was associated with a significantly lower rise over time in Bifidobacterium and infants in the multi-class group experienced a significantly higher increase in Veillonella dispar. CONCLUSIONS: Our findings suggest that intrapartum antibiotics alter the developmental trajectory of the infant gut microbiome, and specific antibiotic types may impact community composition, diversity and keystone immune training taxa. TWEETABLE ABSTRACT: Class of intrapartum antibiotics administered during delivery relates to maturation of infant gut microbiota.

Experiment 1

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Curator: WikiWorks743

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Subjects

Location of subjects

United States of America

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

antimicrobial agent antibiotic,antibiotics,Antibiotika,Antibiotikum,antibiotique,antimicrobial,antimicrobial agents,microbicide,microbicides,antimicrobial agent

Group 0 name Corresponds to the control (unexposed) group for case-control studies

infants (6-weeks) to mothers unexposed to intrapartum antibiotic

Group 1 name Corresponds to the case (exposed) group for case-control studies

infants(6-weeks) to mothers exposed to intrapartum antibiotic

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

vaginally delivered at full-term (>37 weeks of gestation)

Group 0 sample size Number of subjects in the control (unexposed) group

179

Group 1 sample size Number of subjects in the case (exposed) group

87

Lab analysis

Sequencing type

16S

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

V4-V5

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

Illumina

Statistical Analysis

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)?

No

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness

decreased

Simpson Estimator of species richness and species evenness: more weight on species evenness

decreased

Signature 1

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Mark reviewed

Your review change was submitted

Needs review

Curated date: 2020-06-22

Curator: Mst Afroza Parvin

Revision editor(s): WikiWorks743

Source: Table S1, Figure S2 & Text, Figure 1

Description: MZILN results for any intrapartum MZILN model estimates (P<0.05) for ASVs that were significantly associated with intrapartum antibiotic use; Boxplots of alpha diversity scores based on intrapartum antibiotic exposure at (A) 6 weeks (N=266); and (B) 1 year (N=152).

Abundance in Group 1: increased abundance in infants(6-weeks) to mothers exposed to intrapartum antibiotic

NCBI	Links
Oscillospira
Pseudoramibacter ⚠
Varibaculum ⚠
Veillonella dispar

Revision editor(s): WikiWorks743

Signature 2

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Curated date: 2020-06-22

Curator: Mst Afroza Parvin

Revision editor(s): WikiWorks743

Source: Table S1, Figure S2 & Text, Figure 1

Description: MZILN results for any intrapartum MZILN model estimates (P<0.05) for ASVs that were significantly associated with intrapartum antibiotic use; Boxplots of alpha diversity scores based on intrapartum antibiotic exposure at (A) 6 weeks (N=266); and (B) 1 year (N=152).

Abundance in Group 1: decreased abundance in infants(6-weeks) to mothers exposed to intrapartum antibiotic

NCBI	Links
Bacteroides
Bifidobacterium
Blautia
Roseburia
Ruminococcus

Revision editor(s): WikiWorks743

Experiment 2

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Subjects

Location of subjects

United States of America

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

antimicrobial agent antibiotic,antibiotics,Antibiotika,Antibiotikum,antibiotique,antimicrobial,antimicrobial agents,microbicide,microbicides,antimicrobial agent

Group 0 name Corresponds to the control (unexposed) group for case-control studies

infants (1-year) to mothers unexposed to intrapartum antibiotic

Group 1 name Corresponds to the case (exposed) group for case-control studies

infants(1-year) to mothers exposed to intrapartum antibiotic

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

vaginally delivered at full-term (>37 weeks of gestation)

Group 0 sample size Number of subjects in the control (unexposed) group

179

Group 1 sample size Number of subjects in the case (exposed) group

87

Lab analysis

Sequencing type

16S

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

Illumina

Statistical Analysis

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)?

No

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness

decreased

Simpson Estimator of species richness and species evenness: more weight on species evenness

decreased

Signature 1

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2020-06-22

Curator: Mst Afroza Parvin

Revision editor(s): WikiWorks743

Source: Table S1, Figure S2 & Text, Figure 1

Description: MZILN results for any intrapartum MZILN model estimates (P<0.05) for ASVs that were significantly associated with intrapartum antibiotic use; Boxplots of alpha diversity scores based on intrapartum antibiotic exposure at (A) 6 weeks (N=266); and (B) 1 year (N=152).

Abundance in Group 1: increased abundance in infants(1-year) to mothers exposed to intrapartum antibiotic

NCBI	Links
Oscillospira
Pseudoramibacter ⚠
Varibaculum ⚠
Veillonella dispar

Revision editor(s): WikiWorks743

Signature 2

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2020-06-22

Curator: Mst Afroza Parvin

Revision editor(s): WikiWorks743

Source: Table S1, Figure S2 & Text, Figure 1

Description: MZILN results for any intrapartum MZILN model estimates (P<0.05) for ASVs that were significantly associated with intrapartum antibiotic use; Boxplots of alpha diversity scores based on intrapartum antibiotic exposure at (A) 6 weeks (N=266); and (B) 1 year (N=152).

Abundance in Group 1: decreased abundance in infants(1-year) to mothers exposed to intrapartum antibiotic

NCBI	Links
Bacteroides
Bifidobacterium
Blautia
Roseburia

Revision editor(s): WikiWorks743

Experiment 3

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Curated date: 2021/01/10

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Subjects

Location of subjects

United States of America

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

antimicrobial agent antibiotic,antibiotics,Antibiotika,Antibiotikum,antibiotique,antimicrobial,antimicrobial agents,microbicide,microbicides,antimicrobial agent

Group 0 name Corresponds to the control (unexposed) group for case-control studies

infants (6-weeks) to mothers unexposed to antibiotic

Group 1 name Corresponds to the case (exposed) group for case-control studies

infants(6-weeks) to mothers exposed to antibiotics (amoxicillin, penicillin or ampicillin)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

vaginally delivered at full-term (>37 weeks of gestation)

Group 0 sample size Number of subjects in the control (unexposed) group

179

Group 1 sample size Number of subjects in the case (exposed) group

55

Lab analysis

Sequencing type

16S

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

Illumina

Statistical Analysis

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)?

No

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness

unchanged

Simpson Estimator of species richness and species evenness: more weight on species evenness

unchanged

Signature 1

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2020-06-22

Curator: Mst Afroza Parvin

Revision editor(s): WikiWorks743

Source: Table S1, Figure S2 & Text, Figure 1, Figure 3

Description: MZILN results for any intrapartum MZILN model estimates (P<0.05) for ASVs that were significantly associated with intrapartum antibiotic use; Boxplots of alpha diversity scores based on intrapartum antibiotic exposure at (A) 6 weeks (N=266); and (B) 1 year (N=152).

Abundance in Group 1: decreased abundance in infants(6-weeks) to mothers exposed to antibiotics (amoxicillin, penicillin or ampicillin)

NCBI	Links
Bacteroides
Bacteroides ovatus
Bifidobacterium

Revision editor(s): WikiWorks743

Experiment 4

EditHistoryDelete

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Your review change was submittedDuplicate this ExperimentAdd a new Signature

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Curated date: 2021/01/10

Curator: WikiWorks743

Revision editor(s): WikiWorks753, WikiWorks743

Subjects

Location of subjects

United States of America

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

antimicrobial agent antibiotic,antibiotics,Antibiotika,Antibiotikum,antibiotique,antimicrobial,antimicrobial agents,microbicide,microbicides,antimicrobial agent

Group 0 name Corresponds to the control (unexposed) group for case-control studies

infants (1-year) to mothers unexposed to antibiotic

Group 1 name Corresponds to the case (exposed) group for case-control studies

infants(1-year) to mothers exposed to antibiotics (amoxicillin, penicillin or ampicillin)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

vaginally delivered at full-term (>37 weeks of gestation)

Group 0 sample size Number of subjects in the control (unexposed) group

179

Group 1 sample size Number of subjects in the case (exposed) group

55

Lab analysis

Sequencing type

16S

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

Illumina

Statistical Analysis

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)?

No

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness

unchanged

Simpson Estimator of species richness and species evenness: more weight on species evenness

unchanged

Signature 1

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2020-06-22

Curator: Mst Afroza Parvin

Revision editor(s): WikiWorks743

Source: Table S1, Figure S2 & Text, Figure 1, Figure 3

Description: MZILN results for any intrapartum MZILN model estimates (P<0.05) for ASVs that were significantly associated with intrapartum antibiotic use; Boxplots of alpha diversity scores based on intrapartum antibiotic exposure at (A) 6 weeks (N=266); and (B) 1 year (N=152).

Abundance in Group 1: increased abundance in infants(1-year) to mothers exposed to antibiotics (amoxicillin, penicillin or ampicillin)

NCBI	Links
Coprococcus
[Ruminococcus] gnavus

Revision editor(s): WikiWorks743

Signature 2

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2020-06-22

Curator: Mst Afroza Parvin

Revision editor(s): WikiWorks743

Source: Table S1, Figure S2 & Text, Figure 1, Figure 3

Description: MZILN results for any intrapartum MZILN model estimates (P<0.05) for ASVs that were significantly associated with intrapartum antibiotic use; Boxplots of alpha diversity scores based on intrapartum antibiotic exposure at (A) 6 weeks (N=266); and (B) 1 year (N=152).

Abundance in Group 1: decreased abundance in infants(1-year) to mothers exposed to antibiotics (amoxicillin, penicillin or ampicillin)

NCBI	Links
Bacteroides
Bacteroides fragilis
Clostridium
Megamonas
Streptococcus

Revision editor(s): WikiWorks743

Experiment 5

EditHistoryDelete

Mark reviewed

Your review change was submittedDuplicate this ExperimentAdd a new Signature

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Curated date: 2021/01/10

Curator: WikiWorks743

Revision editor(s): WikiWorks753, WikiWorks743

Subjects

Location of subjects

United States of America

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

antimicrobial agent antibiotic,antibiotics,Antibiotika,Antibiotikum,antibiotique,antimicrobial,antimicrobial agents,microbicide,microbicides,antimicrobial agent

Group 0 name Corresponds to the control (unexposed) group for case-control studies

infants (6-weeks) to mothers unexposed to antibiotic

Group 1 name Corresponds to the case (exposed) group for case-control studies

infants(6-weeks) to mothers exposed to multi-class antibiotics

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

vaginally delivered at full-term (>37 weeks of gestation)

Group 0 sample size Number of subjects in the control (unexposed) group

179

Group 1 sample size Number of subjects in the case (exposed) group

12

Lab analysis

Sequencing type

16S

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

Illumina

Statistical Analysis

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)?

No

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness

increased

Simpson Estimator of species richness and species evenness: more weight on species evenness

unchanged

Signature 1

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2020-06-22

Curator: Mst Afroza Parvin

Revision editor(s): WikiWorks743

Source: Table S1, Figure S2 & Text, Figure 1, Figure 3

Description: MZILN results for any intrapartum MZILN model estimates (P<0.05) for ASVs that were significantly associated with intrapartum antibiotic use; Boxplots of alpha diversity scores based on intrapartum antibiotic exposure at (A) 6 weeks (N=266); and (B) 1 year (N=152).

Abundance in Group 1: increased abundance in infants(6-weeks) to mothers exposed to multi-class antibiotics

NCBI	Links
Veillonella dispar

Revision editor(s): WikiWorks743