Data_Sheet_1_Gut Microbiota Dysbiosis and Altered Bile Acid Catabolism Lead to Metabolic Disorder in Psoriasis Mice.docx

Patients with psoriasis tend to have significant comorbidities, such as hyperlipemia, diabetes mellitus, and obesity, which belong to metabolic disorders. The specific mechanism through which psoriasis increases the metabolic disorder risk is uncertain. In this study, we demonstrated that the dysbiotic gut microbiota of 6-month-old psoriasis-like model mice (K14-VEGF-A-transgenic) exacerbated psoriasis disease and induced metabolic disorder when transferred into 2-month-old mice. By 16S rRNA gene sequencing, we confirmed that the Parabacteroides distasonis decreased with age in K14-VEGF mice, and P. distasonis also decreased in the transferred mice. Metabolomic screening identified an altered bile acid profile, including a decrease in chenodeoxycholic acid (CDCA) in the feces of transferred mice. Additionally, CDCA supplements prevented metabolic disorders in K14-VEGF-A-transgenic mice. Consequently, we found that aberrant bile acid metabolism may contribute to metabolic disorder in K14-VEGF-A-transgenic mice, indicating the possibility to prevent and treat the metabolic disorder in psoriasis mice by targeting gut microbial metabolites.

银屑病患者往往伴随多种严重共病，如高脂血症、糖尿病及肥胖，此类病症均属于代谢紊乱范畴。目前银屑病升高代谢紊乱风险的具体机制尚不明确。本研究证实，将6月龄银屑病样模型小鼠（K14-血管内皮生长因子A转基因（K14-VEGF-A-transgenic）的失调肠道菌群移植至2月龄小鼠体内后，可加重银屑病病情并诱发代谢紊乱。通过16S rRNA基因测序，本研究证实K14-VEGF小鼠体内的狄氏副拟杆菌（Parabacteroides distasonis）随年龄增长而丰度降低，且移植受体小鼠体内该菌的丰度同样出现下降。代谢组学筛查显示，移植受体小鼠粪便中的胆汁酸谱发生改变，其中鹅去氧胆酸（chenodeoxycholic acid，CDCA）水平显著降低。此外，补充CDCA可改善K14-VEGF-A转基因小鼠的代谢紊乱。综上，本研究发现异常胆汁酸代谢可能参与K14-VEGF-A转基因小鼠的代谢紊乱进程，提示可通过靶向肠道微生物代谢产物，实现银屑病小鼠代谢紊乱的预防与治疗。