Group IIA secreted phospholipase A(2) controls skin carcinogenesis and psoriasis by shaping the gut microbiota

Besides promoting inflammation by mobilizing lipid mediators, group IIA secreted phospholipase A(2) (sPLA(2)-IIA) prevents bacterial infection by degrading bacterial membranes. Here, we show that, despite the restricted intestinal expression of sPLA(2)-IIA in BALB/c mice, its genetic deletion leads to amelioration of cancer and exacerbation of psoriasis in distal skin. Intestinal expression of sPLA(2)-IIA is reduced after treatment with antibiotics or under germ-free conditions, suggesting its upregulation by gut microbiota. Metagenome, transcriptome, and metabolome analyses have revealed that sPLA(2)-IIA deficiency alters the gut microbiota, accompanied by notable changes in to shaping of the gut microbiota. The skin phenotypes in Pla2g2a(-/-) mice are lost (a) when they genotypes, or (b) when they are housed in a more stringent pathogen-free facility, where Pla2g2a identical. Thus, our results highlight a potentially new aspect of sPLA(2)-IIA as a modulator of gut microbiota, perturbation of which affects distal skin responses.