临床上对糖尿病的治疗主要通过抑制粘膜上皮细胞对糖吸收和转运酶活性控制和通过刺激胰岛素分泌以及补充胰岛素控制血糖升高为治疗手段，由于机体对药物产生耐药和胰岛素抵抗的影响，糖吸收和血糖控制效果不能得以持续，其机制不清楚。最新研究认为肠道优势菌群是维持肠道内环境稳态的“核心菌群”，对粘膜屏障通透性具有重要影响。本研究组前期工作中应用宏基因测序技术发现2型糖尿病患者肠道优势菌群具有明显改变，并观察在动物模型鼠小肠上皮细胞膜表面Na+-K+-ATP酶活性随优势菌群重建而改变明显。本研究拟采用肠道优势菌群分离和重建技术以获得重建靶菌株、基因敲除技术以建立糖尿病动物模型、膜屏障糖通透性评价技术以阐明糖代谢机制，通过重建小肠优势菌群，研究糖尿病模型动物小肠粘膜屏障通透性对糖吸收调节机制，以期通过重建优势菌群调控小肠粘膜通透性影响糖吸收,为糖尿病患者糖代谢紊乱机制的阐明和控制糖吸收治疗提供新策略。

Major method to treat Diabetes is controlling high blood sugar by inhibiting sugar absorption and enzyme activity of transportation on cell membrane,and stimulating secretion and addition insulin,but because of producing tolerance and resistance insulin, the effects of sugar absorption and control high blood sugar can not be continued,and its mechanism is not clear.New study appoints that predominant flora in intestine is a maintain homeostasis “core flora”in internal environment,and a“forgotten organ”which plays importance role in intestinal permeability on membrane barrier.Our group find that predominant flora of type 2 Diabetes is different from health man in intestine,and activity of Na+-K+-ATP enzyme on cell membrane surface changes with predominant flora transform in small intestine.This study will use technique of isolation and reestablishment of intestinal predominant flora to get target flora,and technique of gene knocking out to establish Diabetes animal model,and technique of evaluate of intestinal permeability on membrane barrier to illuminate mechanism of sugar control,and by means of reestablishment predominant flora to study regulation mechanism of intestinal permeability on membrane barrier to sugar absorption so as to via reestablishment predominant flora control change of intestinal permeability on membrane barrier to affect sugar absorption,and to illuminate confusion mechanism of sugar absorption and to provide new strategy in treatment Diabetes.

本研究利用SD大鼠构建糖尿病大鼠模型，并在正常SD大鼠肠道中分离和培养出大鼠肠道优势菌群，将优势菌群回灌给糖尿病大鼠，研究肠道菌群对糖尿病大鼠的影响。按照研究计划，我们分离出11株大鼠肠道优势菌株，构建了糖尿病大鼠模型和糖尿病大鼠肠道菌群紊乱模型，发现糖尿病大鼠与正常大鼠菌群存在明显不同；回灌优势靶菌株重构糖尿病大鼠肠道菌群，发现菌群重建对糖尿病大鼠机能的恢复起到了推动作用。为阐明糖尿病患者糖代谢紊乱机制、病因和治疗提供了新策略，达到了预期目标。目前在整理SCI论文2篇。本研究通过对糖尿病大鼠进行菌群重建发现菌群重建后，糖尿病大鼠的血糖有降低的趋势，接近药物治疗的效果；血清胰岛素水平降低；菌群重建大鼠的血脂水平也比糖尿病模型大鼠有所降低。通过对糖尿病大鼠、糖尿病肠道菌群紊乱大鼠和正常大鼠的十二指肠，空肠和回肠三个肠段进行HE染色观察发现糖尿病菌群失衡组肠粘膜屏障受损最严重；而与糖主动吸收相关性最大的Na+-K+-ATP 酶活性，在糖尿病菌群紊乱组是最高的、糖尿病模型组其次。说明糖尿病菌群结构的改变对糖吸收有促进作用，而通过菌群重建，可以降低这种影响。本研究初步证实了糖尿病大鼠肠道菌群与正常大鼠相比是紊乱的，而对糖尿病大鼠进行菌群重建后，其糖尿病症状有所缓解。为临床上对糖尿病的治疗提供了使用菌群干预的新思路。