肠道菌群在肥胖相关性银屑病中的作用机制研究

中国银屑病发病率与肥胖随着饮食习惯的改变日趋增加。大量的研究表明银屑病与肥胖紧密联系，然而具体机制有待解决。肠道菌群与健康密切相关，主要通过与宿主间的相互作用维持机体稳态。前期研究显示银屑病患者的肠道菌群(如Akker丰度降低) 发生显著改变。而Akker丰度在肥胖、代谢综合症等慢性炎症性疾病中显著降低。我们提高Akker丰度能够显著性抑制IMQ诱导的小鼠银屑病模型，提示肠道菌群在银屑病发生过程中发挥重要作用。本项目将围绕银屑病与肠道菌群，通过16SrRNA及宏基因组测序研究肥胖患者的肠道菌群紊乱；从肠道壁通透性以及细菌代谢产物的角度研究肠道菌群紊乱对于角质形成细胞以及T细胞功能的影响，阐明肠道菌群在银屑病发生过程中的作用和地位；揭示Akker等关键菌群及其代谢产物对于银屑病的作用，构建其相关的菌群互作网络，从一个新的角度阐明银屑病的发病机制，为探讨新的治疗和干预手段提供重要理论基础。

The incidence of psoriasis and obesity in China is increasing with the change of dietary habits. Accumulating evidences demonstrate that obesity is closed to psoriasis pathogenesis, but the details is unclear. The gut microbiota is closely related to health and maintain the body's homeostasis through the interaction with the host. Our previous study showed that gut microbiota had been significantly changed including reduction of Akker abundance in psoriasis patients, compared with healthy control. It was well-known that the Akker abundance is significantly reduced in chronic inflammatory diseases such as obesity and metabolic syndrome. Our previous result showed increasing Akker abundance could attenuate IMQ induced psoriatic like inflammation, suggesting gut microbiota plays key roles in psoriasis development. This study focus on relationship between obesity and psoriasis including investigation gut microbiota disorder in obese patients by 16S and metagenomic sequencing, investigates effect of gut microbiota on keratinocyte and T cell function through intestinal permeability and microbiota products, which illustrate the mechanism about gut microbiota regulation pathogenesis of psoriasis. In addition, we will study the role of Akker etc and its products in psoriasis procedure and generate interaction network about Akker etc. This proposal investigate pathogenesis of psoriasis from a novel perspective and provide solid foundation for developing novel clinical treatments or interventions for psoriasis.