Whole metagenome profiling reveals skin microbiome-dependent susceptibility to atopic dermatitis flare

Study information

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Reviewed Marked as Reviewed by Lwaldron on 2023-4-1

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

27562258

DOI Digital object identifier for electronic documents.

10.1038/nmicrobiol.2016.106

URI

https://www.nature.com/articles/nmicrobiol2016106

Authors

Chng KR, Tay AS, Li C, Ng AH, Wang J, Suri BK, Matta SA, McGovern N, Janela B, Wong XF, Sio YY, Au BV, Wilm A, De Sessions PF, Lim TC, Tang MB, Ginhoux F, Connolly JE, Lane EB, Chew FT, Common JE, Nagarajan N

Journal

Nature microbiology

Year

2016

Whole metagenome analysis has the potential to reveal functional triggers of skin diseases, but issues of cost, robustness and sampling efficacy have limited its application. Here, we have established an alternative, clinically practical and robust metagenomic analysis protocol and applied it to 80 skin microbiome samples epidemiologically stratified for atopic dermatitis (AD). We have identified distinct non-flare, baseline skin microbiome signatures enriched for Streptococcus and Gemella but depleted for Dermacoccus in AD-prone versus normal healthy skin. Bacterial challenge assays using keratinocytes and monocyte-derived dendritic cells established distinct IL-1-mediated, innate and Th1-mediated adaptive immune responses with Staphylococcus aureus and Staphylococcus epidermidis. Bacterial differences were complemented by perturbations in the eukaryotic community and functional shifts in the microbiome-wide gene repertoire, which could exacerbate a dry and alkaline phenotype primed for pathogen growth and inflammation in AD-susceptible skin. These findings provide insights into how the skin microbial community, skin surface microenvironment and immune system cross-modulate each other, escalating the destructive feedback cycle between them that leads to AD flare.

Experiment 1

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Reviewed Marked as Reviewed by Lwaldron on 2023-4-1

Curated date: 2023/03/26

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Lwaldron

Subjects

Location of subjects

Singapore

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

Skin epithelium Skin epithelium,skin epithelium

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Eczema Eczema,eczema

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

Atopic dermatitis case group

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Atopic dermatitis case group with volunteers reporting past atopic dermatitis episodes

Group 0 sample size Number of subjects in the control (unexposed) group

15

Group 1 sample size Number of subjects in the case (exposed) group

19

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

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)?

Yes

Matched on Factors on which subjects have been matched on in a case-control study

age, sex

Alpha Diversity

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

unchanged

Signature 1

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Curated date: 2023/03/30

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Lwaldron, WikiWorks

Source: Supplementary Table 5

Description: Differential microbial abundance between controls and AD case group

Abundance in Group 1: decreased abundance in Atopic dermatitis case group

NCBI	Quality Control	Links
Gemella
Haemophilus
Streptococcus
Veillonella

Revision editor(s): Ufuoma Ejite, Lwaldron, WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Lwaldron on 2023-4-2

Curated date: 2023/03/30

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Lwaldron, WikiWorks

Source: Supplementary Table 5

Description: Differential microbial abundance between controls and AD case group

Abundance in Group 1: increased abundance in Atopic dermatitis case group

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Dermacoccus
Methylobacterium
Deinococcus

Revision editor(s): Ufuoma Ejite, Lwaldron, WikiWorks

Experiment 2

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Reviewed Marked as Reviewed by Lwaldron on 2023-4-1

Curated date: 2023/03/26

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Lwaldron

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Females (controls)

Group 1 name Corresponds to the case (exposed) group for case-control studies

Females (cases)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Atopic dermatitis (AD) case females

Group 0 sample size Number of subjects in the control (unexposed) group

7

Group 1 sample size Number of subjects in the case (exposed) group

11

Lab analysis

Statistical Analysis

Signature 1

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Curated date: 2023/03/30

Curator: Ufuoma Ejite

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Source: Supplementary Figure 6B

Description: Differential microbial abundance between female controls and female AD case group

Abundance in Group 1: decreased abundance in Females (cases)

NCBI	Quality Control	Links
Dermacoccus
Methylobacterium

Revision editor(s): Ufuoma Ejite, Lwaldron, WikiWorks

Experiment 3

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Reviewed Marked as Reviewed by Lwaldron on 2023-4-1

Curated date: 2023/03/26

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Lwaldron

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Males (control)

Group 1 name Corresponds to the case (exposed) group for case-control studies

Males (case)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Atopic dermatitis (AD) case males

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

Matched on Factors on which subjects have been matched on in a case-control study

Not specified

Signature 1

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Reviewed Marked as Reviewed by Lwaldron on 2023-4-2

Curated date: 2023/03/30

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Lwaldron, WikiWorks

Source: Supplementary Figure 6B

Description: Differential microbial abundance between male controls and male AD case group

Abundance in Group 1: decreased abundance in Males (case)

NCBI	Quality Control	Links
Deinococcus
Dermacoccus

Revision editor(s): Ufuoma Ejite, Lwaldron, WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Lwaldron on 2023-4-2

Curated date: 2023/03/30

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Lwaldron, WikiWorks

Source: Supplementary Figure 6B

Description: Differential microbial abundance between male controls and male AD case group

Abundance in Group 1: increased abundance in Males (case)

NCBI	Quality Control	Links
Streptococcus
Gemella
Veillonella
Haemophilus

Revision editor(s): Ufuoma Ejite, Lwaldron, WikiWorks

Experiment 4

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Reviewed Marked as Reviewed by Lwaldron on 2023-4-1

Curated date: 2023/03/30

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Lwaldron

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Normal control

Group 1 name Corresponds to the case (exposed) group for case-control studies

AD cases with no reported cream usage

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

AD cases with no reported cream usage (no emollient creams or topical corticosteroids)

Group 0 sample size Number of subjects in the control (unexposed) group

15

Group 1 sample size Number of subjects in the case (exposed) group

11

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).

Not specified

Signature 1

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Reviewed Marked as Reviewed by Lwaldron on 2023-4-2

Curated date: 2023/03/30

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Lwaldron, WikiWorks

Source: Supplementary Figure 6C

Description: Differential microbial abundance between controls and AD case group with no cream usage

Abundance in Group 1: decreased abundance in AD cases with no reported cream usage

NCBI	Quality Control	Links
Dermacoccus
Methylobacterium

Revision editor(s): Ufuoma Ejite, Lwaldron, WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Lwaldron on 2023-4-2

Curated date: 2023/03/30

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Lwaldron, WikiWorks

Source: Supplementary Figure 6C

Description: Differential microbial abundance between controls and AD case group with no cream usage

Abundance in Group 1: increased abundance in AD cases with no reported cream usage

NCBI	Quality Control	Links
Streptococcus
Gemella
Veillonella
Haemophilus

Revision editor(s): Ufuoma Ejite, Lwaldron, WikiWorks