Temporal dynamics of skin microbiota and immune correlates in psoriasis patients receiving systemic treatment

Abstract

ABSTRACTBackgroundHow skin microbiota in psoriasis patients responded to systematic therapeutics remained unknown.ObjectivesTo profile temporal shifts in transcriptionally active skin microbiota in psoriasis patients receiving systemic therapies.MethodsWe prospectively enrolled 61 psoriasis patients and 29 skin-healthy controls in 2015-2019. Using RNA-based 16S rRNA gene sequencing, we analyzed 969 samples from skin lesions and compared microbial abundance and diversity by therapeutic classes and disease severity.ResultsLesional microbiota in patients on conventional systemics and TNF-αinhibitor was different in relative abundances in Firmicutes (7.83% higher, adjusted P < 0.001) and Proteobacteria (6.98% lower, adjusted P < 0.01) from that in patients on anti-interleukin monoclonal antibodies (anti-ILAb) at baseline. The only difference during treatment was a 1.47% lower abundance in Bacteroides associated with nonbiologics use (adjusted P < 0.01). We identified no indicator taxa by disease severity at baseline yet noticed that a minor relative reduction inCorynebacteriumsp. was associated with clinical responses to treatment.Compared to anti-ILAb, TNF-αinhibitor and nonbiologics were associated with -0.21 lower Shannon Diversity (adjusted P < 0.01) and 0.03 higher Shannon Evenness (adjusted P < 0.01). Results of ordinated principal coordinates analysis revealed that, lesional microbiota from patients of these 3 therapeutic groups was compositionally distinct. Our work also demonstrated concurrent changes in clonal shifts in systemic T cell receptor clonotypes that were associated with systemic use of biologics.ConclusionsCommunity abundances and diversities of skin microbiota may be useful in distinguishing skin microbiota from patients receiving different systemic therapeutics. Specifically, use of anti-ILAb and TNF-αinhibitor was associated with sample-wise microbial abundances and diversities, but not richness, over time. These findings highlighted the potential utility of skin microbiota as biomarkers for personalized treatment plans in patients with moderate-to-severe psoriasis.