Delayed gut microbiota maturation in the first year of life is a hallmark of pediatric allergic disease

From BugSigDB
Reviewed Marked as Reviewed by Folakunmi on 2024-1-29
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Hoskinson C, Dai DLY, Del Bel KL, Becker AB, Moraes TJ, Mandhane PJ, Finlay BB, Simons E, Kozyrskyj AL, Azad MB, Subbarao P, Petersen C, Turvey SE
Journal
Nature communications
Year
2023
Allergic diseases affect millions of people worldwide. An increase in their prevalence has been associated with alterations in the gut microbiome, i.e., the microorganisms and their genes within the gastrointestinal tract. Maturation of the infant immune system and gut microbiota occur in parallel; thus, the conformation of the microbiome may determine if tolerant immune programming arises within the infant. Here we show, using deeply phenotyped participants in the CHILD birth cohort (n = 1115), that there are early-life influences and microbiome features which are uniformly associated with four distinct allergic diagnoses at 5 years: atopic dermatitis (AD, n = 367), asthma (As, n = 165), food allergy (FA, n = 136), and allergic rhinitis (AR, n = 187). In a subset with shotgun metagenomic and metabolomic profiling (n = 589), we discover that impaired 1-year microbiota maturation may be universal to pediatric allergies (AD p = 0.000014; As p = 0.0073; FA p = 0.00083; and AR p = 0.0021). Extending this, we find a core set of functional and metabolic imbalances characterized by compromised mucous integrity, elevated oxidative activity, decreased secondary fermentation, and elevated trace amines, to be a significant mediator between microbiota maturation at age 1 year and allergic diagnoses at age 5 years (βindirect = -2.28; p = 0.0020). Microbiota maturation thus provides a focal point to identify deviations from normative development to predict and prevent allergic disease.

Experiment 1


Reviewed Marked as Reviewed by Folakunmi on 2024-1-29

Curated date: 2023/10/11

Curator: Nwajei Edgar

Revision editor(s): Nwajei Edgar

Subjects

Location of subjects
Canada
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
Dermatitis , Asthma , Food allergy , Allergic rhinitis inflammation of skin,inflammation of the skin,inflammation of zone of skin,inflammatory skin disease,skin inflammation,zone of skin inflammation,Dermatitis,dermatitis,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),Asthma,Food Hypersensitivity,Food intolerance,Food allergy,food allergy,allergic form of rhinitis,allergic rhinitis,Alrh,atopic rhinitis,non-seasonal allergic rhinitis,Perenial allergic rhinitis,perennial allergic rhinitis,pollenosis,seasonal allergic rhinitis,Allergic rhinitis
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
Allergic Children
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Children diagnosed by an expert physician at the 5-year scheduled visit with one or more allergic disorders.
Group 0 sample size Number of subjects in the control (unexposed) group
523
Group 1 sample size Number of subjects in the case (exposed) group
592
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
No Antibiotics exclusion was mentioned

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
Random Forest Analysis
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
Matched on Factors on which subjects have been matched on in a case-control study
age

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-1-29

Curated date: 2023/10/11

Curator: Nwajei Edgar

Revision editor(s): Nwajei Edgar, Peace Sandy, Folakunmi

Source: figure 4C

Description: Comparing species abundance within the 1-year microbiota between children who did or did not receive an allergic diagnosis at 5 years

Abundance in Group 1: decreased abundance in Allergic Children

NCBI Quality ControlLinks
Anaerobutyricum hallii
Anaerostipes hadrus
Blautia wexlerae
Fusicatenibacter saccharivorans

Revision editor(s): Nwajei Edgar, Peace Sandy, Folakunmi

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-1-29

Curated date: 2023/10/11

Curator: Nwajei Edgar

Revision editor(s): Nwajei Edgar, Peace Sandy, Folakunmi

Source: figure 4C

Description: Comparing species abundance within the 1-year microbiota between children who did or did not receive an allergic diagnosis at 5 years

Abundance in Group 1: increased abundance in Allergic Children

NCBI Quality ControlLinks
Eggerthella lenta
Enterococcus faecalis
Escherichia coli
[Clostridium] innocuum
[Clostridium] nexile

Revision editor(s): Nwajei Edgar, Peace Sandy, Folakunmi