Drug design, development and therapy · 2025
PSORI-CM02 Restores Epidermal Differentiation in Psoriasis via the Gut Microbiota-Sphingolipid Axis.
СтатьяНазвание и аннотация: Перевод в очереди
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Wu Yuan, Pan Simin, Yin Chubo, Kong Yunqi, Huo Wanhua, Wang Qiuyue, Wu Jingjing, Li Li, Wei Jianan, Lu Chuanjian, Han Ling, Lu Yue
Аннотация
BACKGROUND: Psoriasis is linked to gut dysbiosis and disturbed sphingolipid metabolism. PSORI-CM02 improves epidermal differentiation, yet its impact on the microbiota-sphingolipid axis remains unknown.
METHODS: Transcriptomics of patient keratinocytes, Carmofur inhibition in IMQ mice, and multi-omics (metabolomics, metagenomics) of skin, lymph nodes and gut were combined. SPF, PGF and GF mice underwent FMT to test microbiota dependency.
RESULTS: Psoriatic lesions showed sphingolipid pathway enrichment. Carmofur enhanced differentiation. PSORI-CM02 lowered PASI, spleen index, and tissue levels of ceramide, S1P, C1P and sphingomyelin while restoring Flg, Krt10 and Krt14. It reduced Turicibacter, Bacteroides, Bifidobacterium and Acetobacter. PSORI-CM02-derived microbiota reproduced therapeutic effects in all FMT settings.
CONCLUSION: PSORI-CM02 reshapes gut microbiota, normalizes sphingolipid metabolism and improves epidermal differentiation to treat psoriasis.
METHODS: Transcriptomics of patient keratinocytes, Carmofur inhibition in IMQ mice, and multi-omics (metabolomics, metagenomics) of skin, lymph nodes and gut were combined. SPF, PGF and GF mice underwent FMT to test microbiota dependency.
RESULTS: Psoriatic lesions showed sphingolipid pathway enrichment. Carmofur enhanced differentiation. PSORI-CM02 lowered PASI, spleen index, and tissue levels of ceramide, S1P, C1P and sphingomyelin while restoring Flg, Krt10 and Krt14. It reduced Turicibacter, Bacteroides, Bifidobacterium and Acetobacter. PSORI-CM02-derived microbiota reproduced therapeutic effects in all FMT settings.
CONCLUSION: PSORI-CM02 reshapes gut microbiota, normalizes sphingolipid metabolism and improves epidermal differentiation to treat psoriasis.