Gut microbiota dysbiosis and altered bile acid catabolism lead to metabolic disorder in psoriasis mice

Abstract

Abstract Patients with psoriasis tend to have significant comorbidities, such as hypertension, diabetes mellitus and obesity, which belong to metabolic disorder. The specific pathways through which psoriasis increases metabolic disorder risk is uncertain. The gut microbiome and gut associated metabolites as important regulators of host energy and substrate metabolism are intricately linked to host metabolic homeostasis. Here we demonstrated that the dysbiotic gut microbiota of aged psoriasis-like model mice(6 months K14-VEGF) exacerbated psoriasis disease and induced the emergence of metabolic disorder when transferred into young mice(2 months K14-VEGF). We used 16S rRNA gene sequencing detected the decrease of Parabacteroides distasonis, an intestinal bacterium, in aged K14-VEGF mice. It has been reported that Parabacteroides distasonis can affect the distribution of bile acid metabolism and benefits the metabolism of host. Metabolomic screening identified an altered distribution of bile acid metabolites, including a decrease in chenodeoxycholic acid(CDCA) in the feces of transferred mice. In addition, supplement with dietary CDCA prevented metabolic disease in K14-VEGF mice. Consequently, we found that aberrant bile acid metabolism may contribute to metabolic disorder in K14-VEGF mice, indicating the possibility to prevent and treat the metabolic disorder by targeting gut microbial metabolites in psoriasis mice.