title: Whole metagenome profiling reveals skin microbiome-dependent susceptibility to atopic dermatitis flare.
abstract: 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.
authors: Genome Institute of Singapore, Singapore 138672, Singapore.
authors: Kern Rei
authors: KR
authors: Chng
authors: Institute of Medical Biology, Singapore 138648, Singapore.
authors: Angeline Su Ling
authors: AS
authors: Tay
authors: Genome Institute of Singapore, Singapore 138672, Singapore.
authors: Chenhao
authors: C
authors: Li
authors: Genome Institute of Singapore, Singapore 138672, Singapore.
authors: Amanda Hui Qi
authors: AH
authors: Ng
authors: Institute of Molecular and Cell Biology, Singapore 138673, Singapore.|Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450001, China.|Institute of Biomedical Studies, Baylor University, Waco, Texas 76798, USA.
authors: Jingjing
authors: J
authors: Wang
authors: Department of Biological Sciences, National University of Singapore, Singapore 117543.
authors: Bani Kaur
authors: BK
authors: Suri
authors: Department of Biological Sciences, National University of Singapore, Singapore 117543.
authors: Sri Anusha
authors: SA
authors: Matta
authors: Singapore Immunology Network, Singapore 138648, Singapore.
authors: Naomi
authors: N
authors: McGovern
authors: Singapore Immunology Network, Singapore 138648, Singapore.
authors: Baptiste
authors: B
authors: Janela
authors: Institute of Medical Biology, Singapore 138648, Singapore.
authors: Xuan Fei Colin C
authors: XF
authors: Wong
authors: Department of Biological Sciences, National University of Singapore, Singapore 117543.
authors: Yang Yie
authors: YY
authors: Sio
authors: Institute of Molecular and Cell Biology, Singapore 138673, Singapore.
authors: Bijin Veonice
authors: BV
authors: Au
authors: Genome Institute of Singapore, Singapore 138672, Singapore.
authors: Andreas
authors: A
authors: Wilm
authors: Genome Institute of Singapore, Singapore 138672, Singapore.
authors: Paola Florez
authors: PF
authors: De Sessions
authors: Division of Plastic, Reconstructive &Aesthetic Surgery, National University Health System, Singapore 119074, Singapore.
authors: Thiam Chye
authors: TC
authors: Lim
authors: National Skin Centre, Singapore 308205, Singapore.
authors: Mark Boon Yang
authors: MB
authors: Tang
authors: Singapore Immunology Network, Singapore 138648, Singapore.
authors: Florent
authors: http://orcid.org/0000-0002-2857-7755
authors: F
authors: Ginhoux
authors: Institute of Molecular and Cell Biology, Singapore 138673, Singapore.|Institute of Biomedical Studies, Baylor University, Waco, Texas 76798, USA.|Department of Microbiology and Immunology, National University of Singapore, Singapore 117545, Singapore.
authors: John E
authors: JE
authors: Connolly
authors: Institute of Medical Biology, Singapore 138648, Singapore.
authors: E Birgitte
authors: EB
authors: Lane
authors: Department of Biological Sciences, National University of Singapore, Singapore 117543.
authors: Fook Tim
authors: http://orcid.org/0000-0003-1337-5146
authors: FT
authors: Chew
authors: Institute of Medical Biology, Singapore 138648, Singapore.
authors: John E A
authors: http://orcid.org/0000-0002-3280-7365
authors: JE
authors: Common
authors: Genome Institute of Singapore, Singapore 138672, Singapore.
authors: Niranjan
authors: N
authors: Nagarajan
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D000818:Animals; D003713:Dendritic Cells / Q000473:pathology; D003876:Dermatitis, Atopic / Q000276:immunology / Q000382:microbiology*; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D008297:Male; D054892:Metagenome; D056186:Metagenomics; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000235:genetics*; D012867:Skin / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000276:immunology*; D013212:Staphylococcus epidermidis / Q000276:immunology*; D055815:Young Adult
chemical_list: D007375:Interleukin-1