在体示踪益生菌治疗肠易激综合征的微生态动力学研究

项目名称： 在体示踪益生菌治疗肠易激综合征的微生态动力学研究

项目编号： No.81330012

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 医药、卫生

项目作者： 李延青

作者单位： 山东大学

项目金额： 290万元

中文摘要： 肠道菌群在肠稳态维持和肠易激综合征（IBS）等多种疾病的发病机制中起重要作用。我们前期研究发现腹泻型IBS患者存在肠上皮屏障功能异常，短期应用乳酸杆菌治疗可以调节IBS患者异常的小肠粘膜的屏障功能，改善患者的腹痛和腹胀症状，并降低患者的总体IBS症状评分。然而益生菌摄入后，益生菌如何在肠道内定植以及益生菌如何影响肠道微生态尚不清楚，益生菌如何调节IBS的发病机制也尚不明确。本课题在前期研究成果的基础上，设计并构建了“示踪基因”，通过在体及离体定位示踪eGFP标记的益生菌体内定植和空间位置变化，并联合16S rDNA高通量测序和宏基因组学研究方法定量分析益生菌和肠道菌群的动态变化，建立消化道菌群的“微生态动力学（microbiodynamics）”， 并进一步探讨微生态影响肠道功能的机制。其研究结果将揭示益生菌对肠道菌群的动力学作用，深入阐明益生菌治疗IBS的机制，优化益生菌的临床应用。

中文关键词： 肠易激综合征;益生菌;微生态动力学;宏基因组;在体示踪

英文摘要： The gut microbiota is both physiologically and pathologically important to intestinal homeostasis and the pathogenesis of irritable bowel syndrome (IBS), among other diseases. We previously found that D-IBS patients are associated with mucosal barrier defect , and that short-term active lactic acid bacteria treatment for D-IBS modulates the patients’ aberrant mucosal barrier function, and reduces abdominal pain and flatulence, thus then reduces the global IBS scores. However, how they colonize in the intestines after administration and affect microbiota are still largely unknown. Further, how the microbiota modulates the IBS pathophysiology is also unknown. Here we will innovatively construct “tracing genes” to track in vivo the colonization and translocation of eGFP labelled probiotics using endomicroscope and laser scanning microscope (LSM), and thus will quantitatively analyze the probiotics in the context of microbiota via 16S rDNA and marcogenome high throughput sequencing. We aim to establish the “microbiodynamics”in the gastrointestinal tract, and elucidate how microbiota modulates intestinal function. This proposal will demonstrate the probiotics’ effect on microbiota and provide insights into mechanisms of treating IBS, which will streamline the clinical application of probiotics.

英文关键词： Irritable Bowel Syndrome;Probiotics;microbiodynamics;Metagenome;In vivo tracking