青稞全谷物介导肠道微生态预防小鼠营养性肥胖的机制研究

Giving the situation that obesity has become a serious global public health problem, it is critical to find practical preventive interventions. Cereals, as the major components of human diet, are closely related to human health. Especially, the inverse relationship between consumption of whole cereal grains and occurrences of chronic diseases has gained increasing attention. Additionally, it is accepted that diet influences human health through modulating the gut microbial ecosystem, particularly through shaping the composition of gut microbiota. Tibetan hull-less barley, uniquely grown in the Tibetan plateau of China, is proved to be effective in preventing development of dietary-induced obesity. In this project, we intend to reveal the mechanism of Tibetan hull-less barley on preventing obesity through observing the interaction of gut microbiota with the host. Both the PCR-DGGE molecular biological squenching technology and NMR / TOF-MS metabolomic technology will be applied to screen the specific gut microbiota that modulated by Tibetan hull-less barley. Despite evaluating the influence of Tibetan hull-less barley on gut microbiota, we will also investigate several main factors that influence gut microbiota on host energy and fat storage metabolism via metabolites- PPAR-γ/NF-ƙB and metabolites- Fiaf signal pathway. We propose to clarify the mechanism of Tibetan hull-less barley on prevention of dietary-induced obesity in mice through the modulation of gut microbiota and its metabolism. As an original research based on Tibetan plant resource, the achievement can help develop whole grain foods with Chinese characteristics. Since stability of the grain market and dietary healthiness of all people are becoming more and more important nowadays, health benefits of Tibetan hull-less barley should be an important subject of both practical and theoretical significance.

肥胖是全球性的公共健康问题，迫切需要寻找切实可行的防治措施。谷物作为人类最基本的膳食组成，与人体健康有着密切关系，其中全谷物对慢性疾病的预防作用备受瞩目。膳食通过肠道内微生物生态系统，尤其是对肠道菌群的调节，是其影响人体健康的重要途径。本课题立足我国特有的谷物资源——青稞，将肠道菌群作为切入点，利用PCR-DGGE分子生物技术和NMR、TOF-MS代谢组学技术进行肠道微生态（肠道菌群结构及其代谢产物）共变异分析，鉴定青稞所调节的特征性肠道细菌。进一步关联肠道微生态与脂肪存储和炎症反应通路中的相关因子（Fiaf、PPAR-γ和NF-κB），最终阐明“青稞全谷物-肠道菌群-肥胖”三者的关系。这是一项我国藏区资源特色的原创性课题，目的在于为创造性地研究开发中国特色的全谷物食品提供理论依据。在“粮食安全”和“全民健康”的时代背景下，本课题的设立彰显出重要的理论和实践价值。

体外模拟消化和发酵研究发现，青稞全谷物（WB）与精制谷物（RB）相比，含有较多能够促进双歧杆菌增殖并提高厚壁菌门/拟杆菌门的比例的益生元成分。建立肠道菌群人源化小鼠，分别以高脂高糖饮食诱导无菌小鼠（GF）和菌群人源化小鼠（HFA）营养性肥胖，而提高WB的摄入量能显著降低由高脂饮食引起的总胆固醇和低密度脂蛋白胆固醇的升高，在一定程度上抑制由高脂饮食造成的脂肪细胞肥大。虽然在高脂高糖饮食中添加WB能够形成一个与高脂高糖饮食相区别的微生物菌群，恢复肥胖小鼠肠道中Megamonas, Parasutterella, Butyricimonas 和Flavonifractor等菌的相对丰度，使菌群结构与普通饲料喂养小鼠的肠道菌群更相似，但该调节作用比较平缓。WB通过上调肝脏中CYP7A1、下调HMG-CoA的表达而降低体内胆固醇水平；通过激活PPARγ、AMPK促进脂肪酸分解代谢来减少脂肪积累，该作用不依赖于肠道菌群。