沙门氏菌和致病性大肠杆菌等变形菌（Proteobacteria），是断奶仔猪腹泻的重要诱因之一。我们前期研究结果证实，GPR109A在肠道屏障和局部炎症调控中发挥着重要的作用。GPR109A还直接（或间接）地影响着变形菌的丰度，但机制不明。因此，本研究拟从GPR109A与变形菌互作的角度，采用代谢组学、细菌基因组学、转录组学、细胞、分子生物学等研究方法，结合生物信息学手段，探讨沙门氏菌和大肠杆菌对猪肠道GPR109A表达和活化的影响，研究GPR109A的活化对变形菌诱导的炎症信号通路的影响，观察GPR109A对肠道局部代谢水平、免疫功能、屏障功能的调控作用，分析上述改变对沙门氏菌和大肠杆菌的定植、增殖能力的影响。预期结果不仅有利于阐明GPR109A与沙门氏菌和大肠杆菌的互作机制，而且为揭示GPR109A在猪肠道屏障调控中的作用提供实验依据，并且有望为解决断奶仔猪腹泻提供新的思路和治疗靶点。

Improvement of intestinal barrier is regarded useful to solve post weanling diarrhea in piglets. Proteobacteria is one of the largest bacteria community, including many pathogenic bacteria, such as Escherichia coli, Salmonella, which affect local intestinal inflammation and lead to diarrhea in animal by lipopolysaccharide (LPS) and their metabolites. GPR109A is involved in many physiological processes including regulation of cell proliferation, inflammatory reactions and metabolism. GPR109A plays an important role in regulating intestinal barrier. Our previous studies confirmed that GPR109A affects the community of intestinal bacteria especially lower the abundance of Proteobacteria, thereby regulating the inflammatory response and intestinal barrier function in CLP induced sepsis. Thus, we hypothesized that the bacteria and its metabolites, regulates the expression and activation of GPR109A which contribute to colon health. Activation of GPR109A affect the epithelium metabolism rate (especially fatty acid levels) and immune status in colon, which play a selective role on the intestinal flora. This study intends to explore the mechanisms of interaction between GPR109A and intestinal Proteobacteria. Metabonomics, bacterial genomics, transcriptomics, cell biology, molecular biology, bioinformatics methods, will be used to investigate the effect of Salmonella and Escherichia coli on expression and activation of porcine intestinal GPR109A, to explore the effects of GPR109A activation on intestinal metabolism, immune function and colonization of Salmonella or Escherichia coli. Reveal the role of the interaction in maintaining intestinal health is supposed to provide an effective approach and therapeutic targets to solve post weaning diarrhea in piglets.