Infant airway microbiota and topical immune perturbations in the origins of childhood asthma

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/28
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Thorsen J, Rasmussen MA, Waage J, Mortensen M, Brejnrod A, Bønnelykke K, Chawes BL, Brix S, Sørensen SJ, Stokholm J, Bisgaard H
Journal
Nature communications
Year
2019
Asthma is believed to arise through early life aberrant immune development in response to environmental exposures that may influence the airway microbiota. Here, we examine the airway microbiota during the first three months of life by 16S rRNA gene amplicon sequencing in the population-based Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort consisting of 700 children monitored for the development of asthma since birth. Microbial diversity and the relative abundances of Veillonella and Prevotella in the airways at age one month are associated with asthma by age 6 years, both individually and with additional taxa in a multivariable model. Higher relative abundance of these bacteria is furthermore associated with an airway immune profile dominated by reduced TNF-α and IL-1β and increased CCL2 and CCL17, which itself is an independent predictor for asthma. These findings suggest a mechanism of microbiota-immune interactions in early infancy that predisposes to childhood asthma.

Experiment 1


Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/28

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Rimsha, Claregrieve1, WikiWorks

Subjects

Location of subjects
Denmark
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
Hypopharynx Laryngeal pharynx,Laryngopharynx,Pars laryngea pharyngis,Hypopharynx
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
asthma Airway hyperreactivity,asthma,Asthma (disorder),Asthma NOS,Asthma NOS (disorder),ASTHMA NOS W (AC) EXAC,Asthma unspecified,Asthma unspecified (disorder),Asthma, Bronchial,Asthma, unspecified,Asthma, unspecified type, with acute exacerbation,Asthma, unspecified type, without mention of status asthmaticus,Asthmas,Asthmatic,BHR - Bronchial hyperreactivity,Bronchial asthma,Bronchial Hyperreactivities,Bronchial hyperreactivity,bronchial hyperreactivity,Bronchial hyperresponsiveness,Bronchial hypersensitivity,chronic obstructive asthma,chronic obstructive asthma with acute exacerbation,chronic obstructive asthma with status asthmaticus,DUST PNEUMONOPATHY NEC,Exercise induced asthma,exercise induced asthma,Exercise-induced asthma,exercise-induced asthma,Exercise-induced asthma (disorder),Hyperreactive airway disease,Hyperreactive airways disease,Hyperreactivities, Bronchial,Hyperreactivity, Bronchial,Other forms of asthma,Pneumonopathy due to inhalation of other dust,Pneumopathy due to inhalation of other dust,Pneumopathy due to inhalation of other dust (disorder),Pneumopathy due to inhalation of other dust NOS,Pneumopathy due to inhalation of other dust NOS (disorder)
Group 0 name Corresponds to the control (unexposed) group for case-control studies
healthy control
Group 1 name Corresponds to the case (exposed) group for case-control studies
child with asthma at age 6
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
asthma at age 6 years diagnosed using a pre-defined validated quantitative symptom algorithm based on parental registration of troublesome lung symptoms on structured daily diary cards from birth, verified by study pediatricians at each clinic visit
Group 0 sample size Number of subjects in the control (unexposed) group
438
Group 1 sample size Number of subjects in the case (exposed) group
135

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

Statistical test
Cox Proportional-Hazards 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)?
Yes


Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/28

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): Claregrieve1, WikiWorks

Source: Supplemental Table 1

Description: Associations between log-relative abundances at one month and asthma development by age six years, assessed with Cox proportional hazards regression

Abundance in Group 1: increased abundance in child with asthma at age 6

NCBI Links
Prevotella
Veillonella

Revision editor(s): Claregrieve1, WikiWorks