Meconium microbiome analysis identifies bacteria correlated with premature birth

Study information

Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

24614698

DOI Digital object identifier for electronic documents.

10.1371/journal.pone.0090784

URI Uniform resource identifier for web resources.

Authors

Ardissone AN, de la Cruz DM, Davis-Richardson AG, Rechcigl KT, Li N, Drew JC, Murgas-Torrazza R, Sharma R, Hudak ML, Triplett EW, Neu J

Journal

PloS one

Year

2014

BACKGROUND: Preterm birth is the second leading cause of death in children under the age of five years worldwide, but the etiology of many cases remains enigmatic. The dogma that the fetus resides in a sterile environment is being challenged by recent findings and the question has arisen whether microbes that colonize the fetus may be related to preterm birth. It has been posited that meconium reflects the in-utero microbial environment. In this study, correlations between fetal intestinal bacteria from meconium and gestational age were examined in order to suggest underlying mechanisms that may contribute to preterm birth. METHODS: Meconium from 52 infants ranging in gestational age from 23 to 41 weeks was collected, the DNA extracted, and 16S rRNA analysis performed. Resulting taxa of microbes were correlated to clinical variables and also compared to previous studies of amniotic fluid and other human microbiome niches. FINDINGS: Increased detection of bacterial 16S rRNA in meconium of infants of <33 weeks gestational age was observed. Approximately 61·1% of reads sequenced were classified to genera that have been reported in amniotic fluid. Gestational age had the largest influence on microbial community structure (R = 0·161; p = 0·029), while mode of delivery (C-section versus vaginal delivery) had an effect as well (R = 0·100; p = 0·044). Enterobacter, Enterococcus, Lactobacillus, Photorhabdus, and Tannerella, were negatively correlated with gestational age and have been reported to incite inflammatory responses, suggesting a causative role in premature birth. INTERPRETATION: This provides the first evidence to support the hypothesis that the fetal intestinal microbiome derived from swallowed amniotic fluid may be involved in the inflammatory response that leads to premature birth.

Experiment 1

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Shaimaa, WikiWorks

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: Meconium Meconium

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: cesarean section caesarean section,cesarean section

Group 0 name Corresponds to the control (unexposed) group for case-control studies: vaginal delivery
Group 1 name Corresponds to the case (exposed) group for case-control studies: C-section
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: the study groups are devided into two groups acc to the gestational age. 1) gestational age < 33 weeks. 2) gestational age >/= 33 weeks
Group 0 sample size Number of subjects in the control (unexposed) group: 19
Group 1 sample size Number of subjects in the case (exposed) group: 33

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: Ion Torrent

Statistical Analysis

Statistical test: Mann-Whitney (Wilcoxon)

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: birth weight, chorioamnionitis, sex, Confounders controlled for: "infant antibiotic" 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.infant antibiotic, Confounders controlled for: "maternal antibiotic" 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.maternal antibiotic, Confounders controlled for: "feeding procedure" 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.feeding procedure, Confounders controlled for: "insurance" 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.insurance, Confounders controlled for: "ROM>18 h" 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.ROM>18 h

Alpha Diversity

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

Signature 1

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Curated date: 2021/01/10

Curator: Rimsha Azhar

Revision editor(s): WikiWorks

Source: Table S6 in File S1

Description: Meconium microbiome related to mode of delivery in premature infants

Abundance in Group 1: increased abundance in C-section

NCBI	Links
Leuconostoc ⚠
Negativicoccus
Vagococcus
Butyrivibrio

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Experiment 2

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Reviewed Marked as Reviewed by Fatima on 2021/07/16

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Rimsha, WikiWorks

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: Meconium Meconium

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: premature birth Birth, Premature,Birth, Preterm,Births, Premature,Births, Preterm,Premature Births,Preterm Birth,Preterm Births,premature birth

Group 0 name Corresponds to the control (unexposed) group for case-control studies: >/=33 weeks
Group 1 name Corresponds to the case (exposed) group for case-control studies: infants <33 weeks gestational age
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: the study groups are devided into two groups acc to the gestational age. 1) gestational age < 33 weeks. 2) gestational age >/= 33 weeks
Group 0 sample size Number of subjects in the control (unexposed) group: 17
Group 1 sample size Number of subjects in the case (exposed) group: 35

Lab analysis

Sequencing type: 16S

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Ion Torrent

Statistical Analysis

Statistical test: Spearman Correlation

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: birth weight, Confounders controlled for: "infant antibiotic" 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.infant antibiotic, sex, Confounders controlled for: "maternal antibiotic" 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.maternal antibiotic, Confounders controlled for: "feeding procedure" 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.feeding procedure, Confounders controlled for: "insurance" 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.insurance, chorioamnionitis, Confounders controlled for: "ROM>18 h" 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.ROM>18 h

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

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Rimsha Azhar

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Source: Table 1

Description: Phyla, family, and genera taxonomy significantly correlated with gestational age

Abundance in Group 1: increased abundance in infants <33 weeks gestational age

NCBI	Links
Bacillota
Bacillaceae
Staphylococcaceae
Enterococcaceae
Lactobacillaceae
Lactobacillaceae
Clostridiaceae
Peptostreptococcaceae
Veillonellaceae
Erysipelotrichaceae
Bifidobacteriaceae
Enterobacteriaceae
Bacillus ⚠
Staphylococcus
Enterococcus
Vagococcus
Lactobacillus
Leuconostoc ⚠
Clostridium
Veillonella
Negativicoccus
Bifidobacterium
Enterobacter ⚠
Citrobacter
Erwinia ⚠
Klebsiella ⚠
Raoultella
Pantoea
Photorhabdus
Tannerella
Actinomycetota