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We aimed to better understand the underlying mechanisms of psoriasis, using a systems biology approach based on transcriptomics and microbiome profiling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We collected the skin tissue biopsies and swabs in both lesional and non\u2010lesional skin of 13 patients with psoriasis, 15 patients with psoriatic arthritis and healthy skin from 12 patients with ankylosing spondylitis. To study the similarities and differences in the molecular profiles between these three conditions, and the associations between the host defence and microbiota composition, we performed high\u2010throughput RNA\u2010sequencing to quantify the gene expression profile in tissues. The metagenomic composition of 16S on local skin sites was quantified by clustering amplicon sequences and counted into operational taxonomic units. We further analysed associations between the transcriptome and microbiome profiling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that lesional and non\u2010lesional samples were remarkably different in terms of their transcriptome profiles. The functional annotation of differentially expressed genes showed a major enrichment in <jats:italic>neutrophil activation<\/jats:italic>. By using co\u2010expression gene networks, we identified a gene module that was associated with local psoriasis severity at the site of biopsy. From this module, we found a \u2018core\u2019 set of genes that was functionally involved in <jats:italic>neutrophil activation<\/jats:italic>, <jats:italic>epidermal cell differentiation<\/jats:italic> and <jats:italic>response to bacteria<\/jats:italic>. Skin microbiome analysis revealed that the abundances of <jats:italic>Enhydrobacter<\/jats:italic>, <jats:italic>Micrococcus<\/jats:italic> and <jats:italic>Leptotrichia<\/jats:italic> were significantly correlated with the genes in <jats:italic>core network<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified a core gene network that associated with local disease severity and microbiome composition, involved in the inflammation and hyperkeratinization in psoriatic skin.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.976","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T04:28:26Z","timestamp":1671510506000},"source":"Crossref","is-referenced-by-count":18,"title":["Multi\u2010omics integration reveals a core network involved in host defence and hyperkeratinization in 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