Shifts in Lachnospira and Clostridium sp. in the 3-month stool microbiome are associated with preschool age asthma

Study information

Needs review

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

27634868

DOI Digital object identifier for electronic documents.

10.1042/CS20160349

URI Uniform resource identifier for web resources.

Authors

Stiemsma LT, Arrieta MC, Dimitriu PA, Cheng J, Thorson L, Lefebvre DL, Azad MB, Subbarao P, Mandhane P, Becker A, Sears MR, Kollmann TR, Mohn WW, Finlay BB, Turvey SE

Journal

Clinical science (London, England : 1979)

Year

2016

Asthma is a chronic disease of the airways affecting one in ten children in Westernized countries. Recently, our group showed that specific bacterial genera in early life are associated with atopy and wheezing in 1-year-old children. However, little is known about the link between the early life gut microbiome and the diagnosis of asthma in preschool age children. To determine the role of the gut microbiota in preschool age asthma, children up to 4 years of age enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) study were classified as asthmatic (n=39) or matched healthy controls (n=37). 16S rRNA sequencing and quantitative PCR (qPCR) were used to analyse the composition of the 3-month and 1-year gut microbiome of these children. At 3 months the abundance of the genus, Lachnospira (L), was decreased (P=0.008), whereas the abundance of the species, Clostridium neonatale (C), was increased (P=0.07) in asthmatics. Quartile analysis of stool composition at 3-months revealed a negative association between the ratio of these two bacteria (L/C) and asthma risk by 4 years of age [quartile 1: odds ratio (OR)=15, P=0.02, CI (confidence interval)= 1.8-124.7; quartile 2: OR=1.0, ns; quartile 3: OR=0.37, ns]. We conclude that opposing shifts in the relative abundances of Lachnospira and C. neonatale in the first 3 months of life are associated with preschool age asthma, and that the L/C ratio may serve as a potential early life biomarker to predict asthma development.

Experiment 1

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Subjects

Location of subjects: Canada

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: 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 controls
Group 1 name Corresponds to the case (exposed) group for case-control studies: asthma at 3 months
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: physician diagnosis of asthma by 4 years of age or was prescribed inhaled asthma medications (inhaled corticosteroids or bronchodilators) from 3 to 4 years of age
Group 0 sample size Number of subjects in the control (unexposed) group: 37
Group 1 sample size Number of subjects in the case (exposed) group: 39

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

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
Matched on Factors on which subjects have been matched on in a case-control study: cesarean section, antibiotic exposure, feeding practices, sex

Alpha Diversity

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

Signature 1

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Source: Figure 1a

Description: Differentially abundant OTUs Identified by Deseq2 analysis at 3 months

Abundance in Group 1: increased abundance in asthma at 3 months

NCBI	Links
Bacillota
Clostridiaceae

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Signature 2

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Source: Figure 1a

Description: Differentially abundant OTUs Identified by Deseq2 analysis at 3 months

Abundance in Group 1: decreased abundance in asthma at 3 months

NCBI	Links
Eubacteriales

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Experiment 2

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Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies: asthma at 1 year

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study: sex, Matched on: "birth mode" is not in the list (abdominalhernia, abnormal glucose tolerance, accute-on-chronic liver failure, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, ...) of allowed values.birth mode, feeding practices, antibiotic exposure