Fig. 3

The dysbiosis of gut microbiota and diet may induce mild and chronic inflammation in psoriasis (by Figdraw, www.figdraw.com). “Leaky gut”, characterized by an increase in intestinal permeability, can induce the release of potent inflammagens such as LPS, LTA, ET, and PG, as well as the intestinal bacterial DNA translocation into blood. Additionally, Citrobacter infections can stimulate the production of IL-22 and IL-17A by ILC3s, thereby contributing to mucosal immunity. The function of ILC3s is also influenced by microbial metabolites SCFAs (including acetate, butyrate, and propionate). Acetate and propionate interact with the FFAR2 receptor on colonic ILC3s, resulting in the activation of AKT or ERK signaling pathways and the subsequent release of IL-22 through the STAT3 axis, while butyrate decreases the amount of ILC3s. Simultaneously, butyrate enhances the differentiation of Treg cells and folate contributes to the maintenance of Tregs, while MCFAs and LCFAs support the cell differentiation of naïve T to Th1 and Th17. The alteration in osmolarity due to a high salt diet leads to the activation of P38/MAPK pathway, subsequently upregulating downstream targets NFAT5 and SGK1, which in turn drive the expression of transcription factors RORγt, IL-23R, IL-17A, and IL-17F, leading to the differentiation of Th17. The upregulated SGK1 promotes IL-23R expression and stabilizes Th17 differentiation through Foxo1 phosphorylation