{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:35:43Z","timestamp":1791588943123,"version":"4.3.4"},"reference-count":75,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea government","award":["RS-2023-00263429"],"award-info":[{"award-number":["RS-2023-00263429"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The gut\u2013skin axis is increasingly implicated in psoriasis pathogenesis, yet the cross-compartment convergence of molecular programs remains incompletely defined. We constructed a conceptual \u201cTriple-Hit\u201d multi-omics framework by integrating five independent public datasets spanning gut microbial functional remodeling (shotgun metagenomics), systemic immune cell methylomes (PBMC and CD8+ T-cell EPIC 850K), and lesional skin regulatory layers (miRNA and bulk RNA-seq). In the gut compartment, functional profiles exhibited a selective reduction in microbial lipid catabolic potential, including decreased fatty acid degradation and a lowered composite lipid degradation score, alongside heterogeneous shifts across SCFA-associated metabolic pathways. Systemically, PBMC methylomes revealed widespread regional remodeling (45,396 DMRs) enriched for membrane-proximal signaling and cytoskeletal programs, while CD8+ T cells showed specific epigenetic alterations in lipid- and glycosphingolipid-associated loci, suggesting a systemic metabolic\u2013epigenetic alignment. In the skin, we identified a compact miRNA signature (168 DE-miRNAs) and a mechanistically interpretable, directionality-constrained miRNA\u2013mRNA bridge that aligns with an AMP-dominant inflammatory transcriptome, consistent with reduced post-transcriptional restraint. Collectively, these findings support a convergent multi-omics framework linking putative microbial metabolic remodeling, systemic immune priming, and cutaneous effector programs. This study provides a systems-level perspective on psoriasis pathogenesis, highlighting the metabolic\u2013epigenetic\u2013transcriptional convergence as a potential avenue for therapeutic intervention.<\/jats:p>","DOI":"10.3390\/life16030516","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T10:49:58Z","timestamp":1774003798000},"page":"516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Triple-Hit Multi-Omics Framework for Psoriasis: Microbial Metabolic Remodeling and Immune Cell Methylome Signature Associated with an AMP-Dominant Lesional Program"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7781-9229","authenticated-orcid":false,"given":"Yoon Kyeong","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju 28644, Republic of Korea"},{"name":"Department of Advanced Bio-Convergence, Chungbuk Health & Science University, Cheongju 28150, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hak Yong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju 28644, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0223-595X","authenticated-orcid":false,"given":"Donghwan","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/S0140-6736(14)61909-7","article-title":"Psoriasis","volume":"386","author":"Boehncke","year":"2015","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1056\/NEJMra0804595","article-title":"Psoriasis","volume":"361","author":"Nestle","year":"2009","journal-title":"N. 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