炎性肠病（IBD），是一类由于机体对肠道细菌异常且持续的免疫反应而引起的自身免疫性疾病，目前尚不能治愈而且容易反复发作。临床用于治疗和缓解IBD的药物主要是TNF抑制剂，而这类药物往往会带来较为严重的毒副作用。肠道菌可以通过分泌次级代谢产物对于宿主的生理功能进行调控，而宿主某些基因的缺陷或过表达也会很大程度地影响IBD的发生和发展。前期研究表明，肠道菌B. fragilis所分泌的PSA以及对于宿主SPAK基因的抑制处理均能够有效抑制IBD的发生或发展。本研究中，我们将首次从肠道共生菌-基因缺陷型宿主相互作用的角度出发，对于肠道菌B.fragilis次级代谢产物组分与SPAK基因缺陷型宿主在IBD病理过程中的分子调控机制进行深入研究。同时希望能够在肠道菌的次级代谢产物中发现有效的SPAK（或相关信号分子）抑制剂或激动剂，以用于后续研究中IBD动物模型的构建和临床药物的研发。

Inflammatory bowel diseases (IBDs) are series of auto-immune diseases caused by inappropriate and continuing immune responses to intestinal bacteria. IBD are incurable thus far but with frequent relapse, tumor necrosis factor (TNF) inhibitors are prevalently used for the treatment and remission of IBDs, but such drugs often lead to serious adverse effects. Intestinal bacteria can regulate physiological function of their host through secreting secondary metabolites, defect or overexpression of certain host genes can greatly affect the occurrence and development of IBD. Previous studies showed that the PSA secreted by intestinal bacteria-Bacteroides fragilis (B. fragilis) or inhibition of host gene SPAK can effectively suppress the occurrence or development of IBD. In this study, we will focus comprehensively on the molecular mechanisms underlying the interaction between B. fragilis secondary metabolites and SPAK deficiency on the pathogenesis of IBD. At the meantime time, try to find an effective inhibitors/agonists of SPAK (or related signaling molecules) in the secondary metabolites of intestinal bacteria for subsequent research to build an animal model of IBD and for clinical drug development.