Abstract
BackgroundPsoriasis is a common chronic inflammatory disease of the skin. We sought to characterize and compare the cutaneous microbiota of psoriatic lesions (lesion group), unaffected contralateral skin from psoriatic patients (unaffected group), and similar skin loci in matched healthy controls (control group) in order to discern patterns that govern skin colonization and their relationship to clinical diagnosis.ResultsUsing high-throughput 16S rRNA gene sequencing, we assayed the cutaneous bacterial communities of 51 matched triplets and characterized these samples using community data analysis techniques. Intragroup Unifrac β diversity revealed increasing diversity from control to unaffected to lesion specimens. Likewise, principal coordinates analysis (PCoA) revealed separation of the lesion samples from unaffected and control along the first axis, suggesting that psoriasis is a major contributor to the observed diversity. The taxonomic richness and evenness decreased in both lesion and unaffected communities compared to control. These differences are explained by the combined increased abundance of the four major skin-associated genera (Corynebacterium, Propionibacterium, Staphylococcus, and Streptococcus), which present a potentially useful predictor for clinical skin type. Psoriasis samples also showed significant univariate decreases in relative abundances and strong classification performance of Cupriavidus, Flavisolibacter, Methylobacterium, and Schlegelella genera versus controls. The cutaneous microbiota separated into two distinct clusters, which we call cutaneotypes: (1) Proteobacteria-associated microbiota, and (2) Firmicutes-associated and Actinobacteria-associated microbiota. Cutaneotype 2 is enriched in lesion specimens compared to control (odds ratio 3.52 (95% CI 1.44 to 8.98), P <0.01).ConclusionsOur results indicate that psoriasis induces physiological changes both at the lesion site and at the systemic level, which select for specific differential microbiota among the assayed clinical skin types. These differences in microbial community structure in psoriasis patients are potentially of pathophysiologic and diagnostic significance.
Highlights
Psoriasis is a common chronic inflammatory disease of the skin
The relevant nature of the independence violation is that the individual significance values for the univariate tests are potentially positively correlated. An example of such correlations is a situation where a statistically significant increase in one taxon abundance between two conditions is accompanied by a balancing decrease in one or more other taxa to have the abundances sum to a constant (1). The effect of this independence violation on the validity of the univariate findings is only mild for the following reasons: (1) the compositional constraint does not remove any true positive association, it only inflates the false negative rates, (2) false negatives are controlled by the False discovery rate (FDR) multiple testing correction procedure, which is designed to take into account positive correlations in P values; (3) the effect of compositional constraint is minimized by the fact that we only focus on highly abundant taxa
Psoriatic lesions trend to decreased taxonomic diversity To assess the changes in α diversity related to psoriasis, we examined the diversity of cutaneous microbiota at the three clinical skin types, in terms of taxonomical richness and evenness at phylum, class, order, family and genus taxonomical level, as well as at the level of Operational taxonomical unit (OTU) defined as sequences with 97% identity to each other
Summary
Psoriasis is a common chronic inflammatory disease of the skin. We sought to characterize and compare the cutaneous microbiota of psoriatic lesions (lesion group), unaffected contralateral skin from psoriatic patients (unaffected group), and similar skin loci in matched healthy controls (control group) in order to discern patterns that govern skin colonization and their relationship to clinical diagnosis. There have been only limited studies of the microbiota in psoriasis patients using molecular methods for the detection of bacterial and fungal taxa [2,3,4,5]. Such studies have involved relatively small numbers of subjects [2], relatively low-throughput bacterial community identification technologies [3,4,5] and unmatched study designs [2]. The major effort through the Human Microbiome Project (HMP) of the US National Institutes of Health (NIH) has resulted in microbial identification of communities in 300 healthy individuals across multiple body sites including several skin sites [16,18,19]
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