两株乳酸菌对小鼠胃肠道微生态的影响及其对幽门螺杆菌感染的预防作 用

Many researches showed that some lactic acid bacteria have high ability of inhibiting H. pylori in vitro, and can inhibit H. pylori colonization and regeneration in the stomach,and reduce the degree of inflammation. The effectiveness and safety of probiotics in the treatment of inhibiting H. pylori infection has been confirmed by many clinical studies. But because it was not yet completely clear of probiotics behavior and biological characteristics in the upper gastrointestinal tract, the mechanism of the probiotics prophylaxis and treatment of H. pylori is not thorough. At the same time, due to the strain specificity, antagonistic mechanism of H. pylori is different, therefore, there were many reserchs need to do about probiotics disturbing H. pylori infection. In recent years, with the deepening of the study of microbes in the human body, it was found that the gut microbiota and human diseases are closely related, not only including gastrointestinal diseases such as colitis, colon cancer, but also metabolic diseases such as obesity and type II diabetes, autoimmune diseases such as rheumatoid arthritis, mental diseases, but there is no research reports about H. pylori infection associated with intestinal microbial. This research intends to evaluation the abilitiy of Bifidobacterium bifidum and Lactobacillus plantarum inhibition of H. pylori in vivo and in vitro, interpret the treatment and mechanism of two strains of probiotics inhibiting the growth of H. pylori and infection through changes in enteric microorganism analysis. The aim of this study is to provide basic data support and probiotics strain resources for the treatment of disease caused by H. pylori.

研究表明部分乳酸菌外具有高效抑杀幽门螺杆菌的能力，而且在体内能够抑制幽门螺杆菌在胃内定植及繁殖生长，减轻幽门螺杆菌相关炎症程度。但由于益生菌在上消化道的行为和生物学特性仍未完全明确，防治幽门螺杆菌的机制尚不明确；同时，由于菌株特异性，拮抗幽门螺杆菌的作用机制各不相同，因而，对益生菌干预幽门螺杆菌感染仍需进行更多方面研究。随着人体微生物研究的不断深入，人们发现肠道微生物与人体多种疾病息息相关，不仅包括消化道类疾病如结肠炎、结肠癌，还包括代谢类疾病如肥胖，免疫性疾病，精神疾病等，都和肠道菌群关系密切，但目前幽门螺杆菌感染与肠道微生物相关的研究报道还很少。本论文拟建立细胞和动物模型，从体内和体外机制探讨乳酸菌抑菌机理及其治疗幽门螺杆菌感染的效果，以期为益生菌联合治疗或预防幽门螺杆菌引起的相关疾病提供益生菌资源和基础数据支持。

幽门螺杆菌可引发诸多消化道疾病，包括胃溃疡甚至胃癌，被世界卫生组织（WHO）归为I类致癌因子。诸多研究表明，益生菌具有减弱抗菌药副作用并调节消化道微生态平衡等多种功能，能够辅助治疗幽门螺杆菌引发的疾病，对其干预幽门螺杆菌感染的研究受到学术界以及产业界的广泛关注。本研究选取两株潜在益生菌菌株：植物乳杆菌ZDY2013和两歧双歧杆菌WBIN03，分析和评价二者拮抗抑制幽门螺杆菌的机制。研究发现植物乳杆菌ZDY2013和两歧双歧杆菌WBIN03可抑制幽门螺杆菌的生长和对胃癌AGS细胞的粘附，并能调节炎症因子相对表达水平。通过构建幽门螺杆菌感染小鼠模型，发现植物乳杆菌ZDY2013灌胃对幽门螺杆菌感染引起的小鼠胃粘膜炎症反应有预防作用，并能预防幽门螺杆菌导致的小鼠胃微生态菌群多样性及结构的改变，更好地维持胃微生态的稳定，对幽门螺杆菌感染具有预防作用。此外，进行了植物乳杆菌ZDY2013全基因组测序并进行了比较基因组分析，并结合比较转录组研究分析了其可能的耐酸机理。