Atopic dermatitis microbiomes stratify into ecologic dermotypes enabling microbial virulence and disease severity.
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.
['Tay|Angeline S L|ASL|', 'Li|Chenhao|C|', 'Nandi|Tannistha|T|', 'Chng|Kern Rei|KR|', 'Andiappan|Anand Kumar|AK|', 'Mettu|Vijaya Saradhi|VS|', 'de Cevins|Camille|C|', 'Ravikrishnan|Aarthi|A|', 'Dutertre|Charles-Antoine|CA|', 'Wong|X F Colin C|XFCC|', 'Ng|Amanda Hui Qi|AHQ|', 'Matta|Sri Anusha|SA|', 'Ginhoux|Florent|F|', 'Rötzschke|Olaf|O|', 'Chew|Fook Tim|FT|', 'Tang|Mark B Y|MBY|', 'Yew|Yik Weng|YW|', 'Nagarajan|Niranjan|N|', 'Common|John E A|JEA|']
D000293:Adolescent D000328:Adult D001419:Bacteria D015415:Biomarkers D016207:Cytokines D003876:Dermatitis, Atopic D005260:Female D006801:Humans D008297:Male D064307:Microbiota D008875:Middle Aged D010641:Phenotype D012720:Severity of Illness Index D012867:Skin D012882:Skin Tests D014774:Virulence D014867:Water D055815:Young Adult
Atopic dermatitis microbiome skin biomarkers nonlesional stratification