肠易激综合征（IBS）是一种发病机制不完全清楚的功能性胃肠病。IBS患者的肠道菌群整体上参与了肠屏障的破坏和肠道微炎症，但庞大的宏基因组中具体哪种细菌或蛋白存在致病性尚不清楚。本研究中我们结合前期工作基础，提出部分IBS患者肠道菌群中存在具核梭杆菌的异常增殖，其表达包括FomA蛋白在内的毒力因子，可能通过TLR2调节肠道ILC3细胞的数量或功能，降低IL-22的分泌和/或增加促炎因子的表达，进而导致IBS患者肠屏障受损和粘膜免疫异常。本研究将在克隆FomA蛋白的基础上，通过流式细胞术、免疫组化、高通量测序等多种研究方法，结合IL-22选择性敲除小鼠模型，验证上述假说。本研究将明确IBS肠道菌群调节的目标、提供新的治疗靶点、奠定新的肠道菌群理论基础。

Irritable bowel syndrome is a functional gastrointestinal disease with unclear pathogenesis. The IBS patients’ gut microbiota as a whole contributed to the intestinal barrier disruption and micro-inflammation. The unknown is which strains or proteins of the huge metagenome is more critically pathogenic. In this protocol, we summarized our previous findings and proposed that: 1) the Fusobacterium nucleatum (FN) over proliferated in the IBS microbiota, 2) the FomA protein, along with other FN virulence factors, might regulate the innate lymphoid cell group 3 (ILC3) via the TLR2 receptor, 3) the decreased IL-22 or increased pro-inflammatory cytokines leads to intestinal barrier disruption and abnormal mucosal immunity. We have cloned the FomA protein and plan to further validate the this hypothesis using multiple methods including flowcytometry, immunohistochemistry, high-through sequencing and IL-22 selective knock mice model. This study will clarify the goal of microbiota modification, provide new therapeutic target, and lay the theoretic found of gut microbiota.