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

Background How skin microbiota in psoriasis patients responded to systematic therapeutics remained unknown. Objectives To profile temporal shifts in transcriptionally active skin microbiota in psoriasis patients receiving systemic therapies. Methods We 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. Results Lesional microbiota in patients on conventional systemics and TNF- α inhibitor 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 in Corynebacterium sp. was associated with clinical responses to treatment. Compared to anti-ILAb, TNF- α inhibitor 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. Conclusions Community 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- α inhibitor 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study was supported by Ministry of Science and Technology, Taiwan [MOST 104-2314-B-182-002, 105-2628-B-182-006, 107-2314-B-418-015 to S Liu]; Chang Gung Medical Foundation [CMRPG3E1971-72 and BMRPE29 to S Liu]; Far Eastern Memorial Hospital [FMRP107-2314B418015 to S Liu]. The funders had no role in preparing or submitting the current work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of two academic centers (Chang Gung Memorial Hospital and National Taiwan University Hospital) where patients were prospectively enrolled gave ethical approval for this work (CGMH 103-6837B, 104-9746B, 201702308B0C501; NTUH 201809061RINB). All patient consent has been obtained. No patient or sample identifiers could be used to identify individual participant in the study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.