EEN通过活化核心微生物组功能维持内环境稳态的机制研究

全肠内营养(Exclusive enteral nutrition, EEN)诱导克罗恩病（Crohn’s disease, CD）缓解的机制不明。已知食物营养价值与宿主核心微生物组功能相关。我们前期发现EEN治疗：①能诱导成人CD缓解并达黏膜愈合；②促使外周血和肠黏膜促炎细胞因子下降；③改变外周血CD4+T淋巴细胞亚群比例。进一步研究发现EEN治疗时：①肠道菌群多样性显著下降；②菌群整体特征与治疗前无差异；③菌群丰度与治疗前不同；④粪便有机酸浓度较前增加。我们推测EEN提供特定的营养环境活化宿主核心微生物组功能维持内环境稳态。我们拟证实：①要素饮食能活化核心微生物组功能；②要素饮食能改善免疫缺陷宿主核心微生物组功能；③核心微生物组基因簇功能活跃改善内环境稳态。明确EEN功效机制，在体内揭示饮食在不同遗传背景下对核心微生物组功能的影响，为理解饮食因素在IBD发病机制中的作用提供依据。

It was less known about the mechanism of exclusive enteral nutrition (EEN) in remission induction of Crohn's disease (CD). The value of diet was associated with functional potential of the host core microbiome. Our previous study showed that: ① EEN could induce the remission of adult CD patients and mucosa healing; ② EEN treatment could decrease the proportion of proinflammatory cytokines in peripheral blood and biopsies；③ EEN treatment could increase the proportion of Treg cells and B lymphocyte and decrease the proportion of Th1 and Th17. In our pre-experimental study, we found that diversity of intetinal microflora decreased after EEN treatment in CD patients, and composition of microbiota in CD patients were similar after EEN treatment comparing to pre-EEN treatment, the relative abundance of Firmicutes increased and Bacteroidetes relative abundance decreased after EEN treatment, accompanied with the increased concentration of organic acid. Therefore, we hyphothesize that EEN could pattern a special nutritional environment and induce the functional potential activation of host core microbiome and maintain the host homeostasis. Thus, we are going to demonstrate that elementary diet can activate the functional potential of host core microbiome, and elementary diet could ameolirate the functional potential of core microbiome in the context of inflammation, and activation of functional potential in core microbiome could maintain the homeostasis. These will clarify the mechanism of EEN treatment, and reveal the impact of the dietary factor synergize the genetic backgroud on the core microbiome functional potential, and give insights into the pathogenesis of inflammatory bowel disease.