PSORI-CM02 Restores Epidermal Differentiation in Psoriasis via the Gut Microbiota-Sphingolipid Axis.

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.