Features of the bronchial bacterial microbiome associated with atopy, asthma, and responsiveness to inhaled corticosteroid treatment

From BugSigDB
Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/13
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Durack J, Lynch SV, Nariya S, Bhakta NR, Beigelman A, Castro M, Dyer AM, Israel E, Kraft M, Martin RJ, Mauger DT, Rosenberg SR, Sharp-King T, White SR, Woodruff PG, Avila PC, Denlinger LC, Holguin F, Lazarus SC, Lugogo N, Moore WC, Peters SP, Que L, Smith LJ, Sorkness CA, Wechsler ME, Wenzel SE, Boushey HA, Huang YJ
Journal
The Journal of allergy and clinical immunology
Year
2017
Keywords:
16S ribosomal RNA, Asthma, T(H)2 inflammation, atopy, bacteria, corticosteroids, metabolic pathways, microbiome, short-chain fatty acids, three-gene mean
BACKGROUND: Compositional differences in the bronchial bacterial microbiota have been associated with asthma, but it remains unclear whether the findings are attributable to asthma, to aeroallergen sensitization, or to inhaled corticosteroid treatment. OBJECTIVES: We sought to compare the bronchial bacterial microbiota in adults with steroid-naive atopic asthma, subjects with atopy but no asthma, and nonatopic healthy control subjects and to determine relationships of the bronchial microbiota to phenotypic features of asthma. METHODS: Bacterial communities in protected bronchial brushings from 42 atopic asthmatic subjects, 21 subjects with atopy but no asthma, and 21 healthy control subjects were profiled by using 16S rRNA gene sequencing. Bacterial composition and community-level functions inferred from sequence profiles were analyzed for between-group differences. Associations with clinical and inflammatory variables were examined, including markers of type 2-related inflammation and change in airway hyperresponsiveness after 6 weeks of fluticasone treatment. RESULTS: The bronchial microbiome differed significantly among the 3 groups. Asthmatic subjects were uniquely enriched in members of the Haemophilus, Neisseria, Fusobacterium, and Porphyromonas species and the Sphingomonodaceae family and depleted in members of the Mogibacteriaceae family and Lactobacillales order. Asthma-associated differences in predicted bacterial functions included involvement of amino acid and short-chain fatty acid metabolism pathways. Subjects with type 2-high asthma harbored significantly lower bronchial bacterial burden. Distinct changes in specific microbiota members were seen after fluticasone treatment. Steroid responsiveness was linked to differences in baseline compositional and functional features of the bacterial microbiome. CONCLUSION: Even in subjects with mild steroid-naive asthma, differences in the bronchial microbiome are associated with immunologic and clinical features of the disease. The specific differences identified suggest possible microbiome targets for future approaches to asthma treatment or prevention.

Experiment 1


Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/13

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, ChiomaBlessing

Subjects

Location of subjects
United States of America
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
Bronchus Bronchi,Bronchial tissue,Bronchial trunk,Bronchus,bronchus
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Atopic asthma allergic asthma,Atopic asthma,atopic asthma
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
atopic asthma
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients who have atopic asthma
Group 0 sample size Number of subjects in the control (unexposed) group
21
Group 1 sample size Number of subjects in the case (exposed) group
42
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 months

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

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
raw counts
Statistical test
Negative Binomial Regression
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.1
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/13

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): Claregrieve1, WikiWorks

Source: Figure 2a, Supplemental Table S4

Description: Differentially abundant microbial taxa in atopic asthmatic (AA) subjects compared with healthy controls (HC)

Abundance in Group 1: increased abundance in atopic asthma

NCBI Quality ControlLinks
Actinomyces
Alloprevotella tannerae
Anaerovorax
Campylobacter
Fusobacterium
Haemophilus
Kingella
Lactobacillus iners
Neisseria
Neisseria subflava
Porphyromonas
Prevotella
Segatella copri
Sphingopyxis
Sphingopyxis alaskensis
Treponema
Treponema amylovorum
Veillonella
Veillonella dispar

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/13

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): Claregrieve1, WikiWorks

Source: Figure 2a, Supplemental Table S4

Description: Differential microbial abundance between atopic asthmatic (AA) subjects compared with healthy controls (HC)

Abundance in Group 1: decreased abundance in atopic asthma

NCBI Quality ControlLinks
Actinobacillus
Kocuria palustris
Lacticaseibacillus zeae
Lactobacillus
Leptotrichia
Methylobacterium
Peptostreptococcus

Revision editor(s): Claregrieve1, WikiWorks

Experiment 2


Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/13

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
atopic no asthma
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
atopic nonasthmatic subjects
Group 1 sample size Number of subjects in the case (exposed) group
21

Lab analysis

Statistical Analysis

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/13

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): Claregrieve1, WikiWorks

Source: Figure 2b, Supplemental Table S5

Description: Differential microbial abundance between atopic nonasthmatic (ANA) subjects compared with healthy controls (HC)

Abundance in Group 1: increased abundance in atopic no asthma

NCBI Quality ControlLinks
Actinomyces
Aggregatibacter
Aggregatibacter segnis
Corynebacterium
Flexispira
Fusobacterium
Granulicatella
Haemophilus
Haemophilus influenzae
Moraxella
Prevotella melaninogenica
Hoylesella nanceiensis
Selenomonas
Sharpea
Sphingopyxis
Sphingopyxis alaskensis
Treponema amylovorum
Veillonella
Veillonella dispar

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/13

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): Claregrieve1, WikiWorks

Source: Figure 2b, Supplemental Table S5

Description: Differential microbial abundance between atopic nonasthmatic (ANA) subjects compared with healthy controls (HC)

Abundance in Group 1: decreased abundance in atopic no asthma

NCBI Quality ControlLinks
Helicobacter
Lacticaseibacillus zeae
Lactobacillus
Leptotrichia
Parvimonas
Porphyromonas
Prevotella
Pseudomonas
Streptococcus

Revision editor(s): Claregrieve1, WikiWorks

Experiment 3


Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/13

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
atopic no asthma
Group 1 name Corresponds to the case (exposed) group for case-control studies
atopic asthma
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
atopic asthma subjects
Group 1 sample size Number of subjects in the case (exposed) group
42

Lab analysis

Statistical Analysis

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/13

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): Claregrieve1, WikiWorks

Source: Figure 2c, Supplemental Table S6

Description: Differential microbial abundance between atopic asthmatic (AA) subjects compared with atopic nonasthmatic (ANA) subjects

Abundance in Group 1: increased abundance in atopic asthma

NCBI Quality ControlLinks
Dialister
Fusobacterium
Haemophilus
Leptotrichia
Mycoplasma
Neisseria subflava
Prevotella
Prevotella intermedia
Selenomonas

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/13

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): Claregrieve1, WikiWorks

Source: Figure 2c, Supplemental Table S6

Description: Differential microbial abundance between atopic asthmatic (AA) subjects compared with atopic nonasthmatic (ANA) subjects

Abundance in Group 1: decreased abundance in atopic asthma

NCBI Quality ControlLinks
Aggregatibacter
Aggregatibacter segnis
Allobaculum
Bacteroides fragilis
Capnocytophaga ochracea
Corynebacterium
Flavobacterium columnare
Flexispira
Haemophilus influenzae
Haemophilus parainfluenzae
Lacticaseibacillus zeae
Lactobacillus
Porphyromonas
Segatella copri
Hoylesella nanceiensis
Sharpea
Sphingopyxis
Sphingopyxis alaskensis
Streptococcus
Treponema amylovorum
Mediterraneibacter gnavus

Revision editor(s): Claregrieve1, WikiWorks

Experiment 4


Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
nonresponder
Group 1 name Corresponds to the case (exposed) group for case-control studies
inhaled corticosteroid responder
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
inhaled corticosteroid (ICS) responder
Group 0 sample size Number of subjects in the control (unexposed) group
10
Group 1 sample size Number of subjects in the case (exposed) group
15

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): Claregrieve1, WikiWorks, Merit

Source: Figure 6b

Description: Differential relative taxon abundance in inhaled corticosteroid (ICS) responders versus nonresponders among those with atopic asthma

Abundance in Group 1: increased abundance in inhaled corticosteroid responder

NCBI Quality ControlLinks
Streptococcaceae
Erysipelotrichaceae
Fusobacteriaceae
Lachnospiraceae
Moraxellaceae
Neisseriaceae
Peptostreptococcaceae
Sphingomonadaceae
Veillonellaceae
unclassified Mogibacterium
Streptococcus

Revision editor(s): Claregrieve1, WikiWorks, Merit

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): Claregrieve1, WikiWorks

Source: Figure 6b

Description: Differential relative taxon abundance in inhaled corticosteroid (ICS) responders versus nonresponders among those with atopic asthma

Abundance in Group 1: decreased abundance in inhaled corticosteroid responder

NCBI Quality ControlLinks
Actinomycetaceae
Aerococcaceae
Azotobacter group
Flavobacteriaceae
Lactobacillaceae
Microbacteriaceae
Mycoplasmataceae
Pasteurellaceae
Porphyromonadaceae
Prevotellaceae
Spirochaetaceae
Weeksellaceae
Gemella

Revision editor(s): Claregrieve1, WikiWorks

Experiment 5


Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
baseline (corticosteroid treatment group)
Group 1 name Corresponds to the case (exposed) group for case-control studies
post inhaled corticosteroid treatment
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
asthma patients after inhaled corticosteroid treatment
Group 0 sample size Number of subjects in the control (unexposed) group
8
Group 1 sample size Number of subjects in the case (exposed) group
8

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): WikiWorks

Source: Text, Figure 6d

Description: Taxa differentially expressed in asthmatic subjects who responded to treatment after inhaled corticosteroid (ICS) treatment

Abundance in Group 1: increased abundance in post inhaled corticosteroid treatment

NCBI Quality ControlLinks
Microbacteriaceae
Neisseria
Moraxella
Spirochaetaceae
Actinomycetaceae
Mycoplasmataceae

Revision editor(s): WikiWorks

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): WikiWorks

Source: Text, Figure 6d

Description: Taxa differentially expressed in asthmatic subjects who responded to treatment after inhaled corticosteroid (ICS) treatment

Abundance in Group 1: decreased abundance in post inhaled corticosteroid treatment

NCBI Quality ControlLinks
Acholeplasmataceae
Lactobacillaceae
Prevotellaceae
Lachnospiraceae
Peptostreptococcaceae
Fusobacterium
Dialister

Revision editor(s): WikiWorks

Experiment 6


Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
baseline (placebo group)
Group 1 name Corresponds to the case (exposed) group for case-control studies
post placebo treatment
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
placebo treatment

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): WikiWorks

Source: Text, Figure 6d

Description: Taxa differentially expressed in asthmatic subjects after placebo treatment

Abundance in Group 1: increased abundance in post placebo treatment

NCBI Quality ControlLinks
Eikenella
Spirochaetaceae
Mycoplasmataceae

Revision editor(s): WikiWorks

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): WikiWorks

Source: Text, Figure 6d

Description: Taxa differentially expressed in asthmatic subjects after placebo treatment

Abundance in Group 1: decreased abundance in post placebo treatment

NCBI Quality ControlLinks
Acinetobacter
Actinomycetaceae
Prevotellaceae
Peptostreptococcaceae

Revision editor(s): WikiWorks

Experiment 7


Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

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
atopic asthma
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
atopic asthma subjects
Group 0 sample size Number of subjects in the control (unexposed) group
21
Group 1 sample size Number of subjects in the case (exposed) group
42

Lab analysis

Statistical Analysis

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): WikiWorks

Source: Supplemental Figure E4a

Description: Bacterial phylum significantly enriched or depleted in relative abundance in atopic asthmatic (AA) subjects compared with healthy controls (HC)

Abundance in Group 1: increased abundance in atopic asthma

NCBI Quality ControlLinks
Actinomycetota
Bacteroidota
Fusobacteriota
Pseudomonadota
Spirochaetota

Revision editor(s): WikiWorks

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): WikiWorks

Source: Supplemental Figure E4a

Description: Bacterial phylum significantly enriched or depleted in relative abundance in atopic asthmatic (AA) subjects compared with healthy controls (HC)

Abundance in Group 1: decreased abundance in atopic asthma

NCBI Quality ControlLinks
Bacillota

Revision editor(s): WikiWorks

Experiment 8


Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
atopic no asthma
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
atopic no asthma
Group 1 sample size Number of subjects in the case (exposed) group
21

Lab analysis

Statistical Analysis

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): WikiWorks

Source: Supplemental Figure E4b

Description: Bacterial phylum significantly enriched or depleted in relative abundance in atopic nonasthmatic (ANA) subjects compared with healthy controls (HC)

Abundance in Group 1: increased abundance in atopic no asthma

NCBI Quality ControlLinks
Actinomycetota
Bacillota
Pseudomonadota

Revision editor(s): WikiWorks

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): WikiWorks

Source: Supplemental Figure E4b

Description: Bacterial phylum significantly enriched or depleted in relative abundance in atopic nonasthmatic (ANA) subjects compared with healthy controls (HC)

Abundance in Group 1: decreased abundance in atopic no asthma

NCBI Quality ControlLinks
Bacteroidota
Fusobacteriota
Spirochaetota

Revision editor(s): WikiWorks

Experiment 9


Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
atopic no asthma
Group 1 name Corresponds to the case (exposed) group for case-control studies
atopic asthma
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
atopic asthma subjects
Group 1 sample size Number of subjects in the case (exposed) group
42

Lab analysis

Statistical Analysis

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): WikiWorks

Source: Supplemental Figure E4c

Description: Bacterial phylum significantly enriched or depleted in relative abundance in atopic asthmatic (AA) subjects compared with atopic nonasthmatic (ANA)

Abundance in Group 1: increased abundance in atopic asthma

NCBI Quality ControlLinks
Bacteroidota
Fusobacteriota

Revision editor(s): WikiWorks

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/14

Curated date: 2021/01/10

Curator: Lucy Mellor

Revision editor(s): WikiWorks

Source: Supplemental Figure E4c

Description: Bacterial phylum significantly enriched or depleted in relative abundance in atopic asthmatic (AA) subjects compared with atopic nonasthmatic (ANA)

Abundance in Group 1: decreased abundance in atopic asthma

NCBI Quality ControlLinks
Actinomycetota
Bacillota
Pseudomonadota
Spirochaetota

Revision editor(s): WikiWorks