Metformin Treatment Protects Mice from Glucose-Promoted Psoriasiform Dermatitis through Enrichment of Akkermansia muciniphila with Modulation of Bacterial Tryptophan Metabolites.

Abstract

Although diet has been regarded as a potential environmental risk factor for psoriasis, the precise contribution of specific dietary components, such as sugar, to its pathogenesis remains uncertain. Metformin, a primary medication for type II diabetes mellitus, has been documented to yield improvements in psoriasis. Earlier research indicates that the antihyperglycemic impact of metformin is associated with changes in gut microbiota. Nonetheless, the role of gut microbiota in the antipsoriatic effects of metformin remains unclear. In this study, we showed that 4 weeks of glucose intake exacerbated psoriasiform dermatitis (PsD) in mice, which resolved with oral metformin treatment. The exacerbation and resolution of PsD were mediated through effects on the gut microbiota. Supplementation with Akkermansia muciniphila, enriched by metformin, or Amuc_1100 improved PsD in glucose-fed mice but not in the control mice. Glucose intake resulted in reduced serum levels of indole-3-acetic acid, a microbial tryptophan metabolite, which were reversed by A muciniphila and Amuc_1100 treatment. Oral administration and intradermal injection of indole-3-acetic acid protected mice from glucose-promoted PsD with suppressed expression of antimicrobial peptides, specifically S100A8, in the epidermis. Collectively, increases of A muciniphila through metformin treatment led to reversal of glucose-promoted PsD in mice, possibly through production of the microbial tryptophan metabolite indole-3-acetic acid.