基于肠道微生物Niche理论研究嘎日迪散调节UC模型小鼠肠道菌群的分子靶点

Ulcerative colitis (UC) is one of the most intractable diseases, and there are no effective therapies currently. Mongolian Herbal Medicine GaRiDi pulvis is the specific medicine in the treatment of UC, with many years of clinical and experimental research. Research group found the difference of intestinal flora was associated with the structure of the colon in the preliminary study on mechanisms of correcting intestinal flora imbalance in UC model rat. The discovery happened to have the same view with the gut microbes Niche theory. We adopt DSS-induced mice UC model. This research, on the basis of previous work, the intestinal mucus inside and outside layer and the intestinal contents flora changing as the breakthrough point of the research, is about to use qRT-PCR method, 16SrRNA gene high-throughput sequencing technologies, Metatranscriptome sequencing technology to analyze the intestinal contents’ microorganism amount, microbial species and abundance of different parts and microbial function variation in the slime layer and the mucous layer. Finally, we are about to clarify the differences among the slime layer, the mucous layer and the intestinal contents on the bacterial species and metabolism, reveal the relationship between the intestinal flora imbalance of different parts and the pathogenesis of UC, clear GaRiDi pulvis’s molecular targets of regulating intestinal flora and explain the theory of “Baoru disease” and the key rule of " Shugan turbidity, decreasing viscosity and detoxification, and transiting Heyi” in Mongolian medicine.

溃疡性结肠炎（UC）是现代难治病之一，目前尚无根治办法。嘎日迪散是治疗UC特效蒙药，具有多年临床和实验研究基础。课题组在前期对嘎日迪散纠正UC模型肠道菌群失衡研究中发现肠道菌群差异似乎与结肠结构相关，该发现与结肠微生物Niche理论不谋而合。本课题在前期工作的基础上，拟以肠道内、外粘液层、及肠道内容物菌群变化为研究的切入点，通过建立DSS诱导的UC小鼠模型，以嘎日迪散为研究载体，利用qRT-PCR方法、菌群16SrRNA基因高通量测序、宏基因组测序等，分析外、内粘液层及肠道内容物微生物总量、各部位微生物种类、丰度及微生物功能变化。最终阐明外粘液层、内粘液层以及肠道内容物在细菌种类、代谢等方面的差别，揭示各部位肠道菌群失衡与UC发病的相互关系，明确嘎日迪散调节肠道菌群的分子作用靶点，深层次阐释蒙医“包如病”理论及“疏肝除浊、消粘解毒、通行赫依”治则的科学内涵。

溃疡性结肠炎（UC）是现代难治病之一，目前尚无根治办法。嘎日迪散是治疗UC特效蒙药，具有多年临床和实验研究基础。课题组在前期对嘎日迪散纠正UC模型肠道菌群失衡研究中发现肠道菌群差异似乎与结肠结构相关，该发现与结肠微生物Niche理论不谋而合。本课题在前期工作的基础上，拟以肠道内、外粘液层、及肠道内容物菌群变化为研究的切入点，通过建立DSS诱导的UC小鼠模型，以嘎日迪散为研究载体，利用qRT-PCR方法、菌群16SrRNA基因高通量测序、宏基因组测序等，分析外、内粘液层及肠道内容物微生物总量、各部位微生物种类、丰度及微生物功能变化。最终阐明外粘液层、内粘液层以及肠道内容物在细菌种类、代谢等方面的差别，揭示各部位肠道菌群失衡与UC发病的相互关系，明确嘎日迪散调节肠道菌群的分子作用靶点，深层次阐释蒙医“包如病”理论及“疏肝除浊、消粘解毒、通行赫依”治则的科学内涵。