Atopic dermatitis microbiomes stratify into ecologic dermotypes enabling microbial virulence and disease severity

Atopic dermatitis microbiomes stratify into ecologic dermotypes enabling microbial virulence and disease severity

Journal of Allergy and Clinical Immunology

10.1016/j.jaci.2020.09.031

http://dx.doi.org/10.1016/j.jaci.2020.09.031

Angeline S.L. Tay, Chenhao Li, Tannistha Nandi, Kern Rei Chng, Anand Kumar Andiappan, Vijaya Saradhi Mettu, Camille de Cevins, Aarthi Ravikrishnan, Charles-Antoine Dutertre, X.F. Colin C. Wong, Amanda Hui Qi Ng, Sri Anusha Matta, Florent Ginhoux, Olaf Rotzschke, Fook Tim Chew, Mark B.Y. Tang, Yik Weng Yew, Niranjan Nagarajan, John E.A. Common

Genetics and Molecular Biology

08 October 2020

Tay, A. S. L., Li, C., Nandi, T., Chng, K. R., Andiappan, A. K., Mettu, V. S., de Cevins, C., Ravikrishnan, A., Dutertre, C.-A., Wong, X. F. C. C., Ng, A. H. Q., Matta, S. A., Ginhoux, F., Rötzschke, O., Chew, F. T., Tang, M. B. Y., Yew, Y. W., Nagarajan, N., & Common, J. E. A. (2021). Atopic dermatitis microbiomes stratify into ecologic dermotypes enabling microbial virulence and disease severity. Journal of Allergy and Clinical Immunology, 147(4), 1329–1340. https://doi.org/10.1016/j.jaci.2020.09.031

Background Atopic dermatitis (AD) is a common skin disease affecting up to 20% of the global population, with significant clinical heterogeneity and limited information about molecular subtypes and actionable biomarkers. Although alterations in the skin microbiome have been described in subjects with AD during progression to flare state, the prognostic value of baseline microbiome configurations has not been explored. Objective Our aim was to identify microbial signatures on AD skin that are predictive of disease fate. Methods Nonlesional skin of patients with AD and healthy control subjects were sampled at 2 time points separated by at least 4 weeks. Using whole metagenome analysis of skin microbiomes of patients with AD and control subjects (n = 49 and 189 samples), we identified distinct microbiome configurations (dermotypes A and B). Blood was collected for immunophenotyping, and skin surface samples were analyzed for correlations with natural moisturizing factors and antimicrobial peptides. Results Dermotypes were robust and validated across 2 additional cohorts (63 individuals), with strong enrichment of subjects with AD in dermotype B. Dermotype B was characterized by reduced microbial richness, depletion of Cutibacterium acnes, Dermacoccus and Methylobacterium species, individual-specific outlier abundance of Staphylococcus species (eg, S epidermidis, S capitis, S aureus), and enrichment in metabolic pathways (eg, branched chain amino acids and arginine biosynthesis) and virulence genes (eg, β-toxin, δ-toxin) that defined a pathogenic ecology. Skin surface and circulating host biomarkers exhibited a distinct microbial-associated signature that was further reflected in more severe itching, frequent flares, and increased disease severity in patients harboring the dermotype B microbiome. Conclusion We report distinct clusters of microbial profiles that delineate the role of microbiome configurations in AD heterogeneity, highlight a mechanism for ongoing inflammation, and provide prognostic utility toward microbiome-based disease stratification.

Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

This research / project is supported by the National Healthcare Group/ A*STAR /Nanyang Technological University - Skin Research Grant
Grant Reference no. : SRG/14032

This research / project is supported by the A*STAR - IAF-SPF - Skin Biology Basic Research
Grant Reference no. : SPF2013/004

This research / project is supported by the A*STAR - IAF-SPF grants - Genetic Orphan Diseases Adopted: Fostering Innovation Therapy
Grant Reference no. : SFP2012/005

This research / project is supported by the A*STAR - IAF-PP grant - Asian Skin Microbiome Program
Grant Reference no. : H18/01/a0/016

https://oar.a-star.edu.sg/communities-collections/articles/20064

0091-6749

Skin Research Lab