肠道菌群与糖尿病

摘要： 近年来, 肠道菌群与糖尿病的关系成为研究热点。随着对肠道菌群认识的深入, 肠道菌群作为环境因素在调节免疫及代谢性疾病发生中的作用逐渐被大家认识。目前国内外已有大量研究关注肠道菌群影响肥胖和糖尿病的发病机制, 也有研究发现肠道菌群能够从食物难以消化的成分中获取能量, 从而影响人体的能量平衡和代谢。人们通过基因组测序的方法揭示不同类型糖尿病患者肠道菌群的组成、 丰度等, 并在动物体内进行验证, 明确和糖尿病相关的细菌功能。肠道菌群携带的遗传信息可能是未来治疗糖尿病的新突破口。关于2型糖尿病 （T2DM） 及1 型糖尿病 （T1DM） 肠道菌群的研究较多, 但妊娠期糖尿病 （GDM） 肠道菌群的相关研究报道较少。因此, 本文对不同类型糖尿病的肠道菌群特点及肠道菌群参与糖尿病发生的机制作一综述。     

肠道菌群与代谢性疾病关系研究进展

代谢性疾病是一系列机体代谢异常疾病的总称, 包括肥胖、糖尿病、非酒精性肝病等。人类肠道中有数以百亿的细菌, 其产生的代谢产物可与人类宿主相互作用, 从而影响着人类的健康。肠道微生物群与人类宿主的代谢健康密切相关, 在异常情况下可能会导致各种常见的代谢疾病, 如肥胖、2型糖尿病、非酒精性肝病、心肺代谢疾病、营养不良等。本文讨论了肠道菌群与常见的代谢性疾病的关系、致病机制, 基于肠道菌群的代谢性疾病的治疗和预防方法, 为代谢性疾病的治疗提供新方向。     

肠道菌群变化与2型糖尿病发病关系的研究进展

世界卫生组织统计数据表明,2014年全球估计有4.22亿成人患有糖尿病,而我国又是糖尿病高发国,不管在生活上还是经济上,严重影响患者的生活质量。糖尿病的病因复杂,遗传因素、生活习惯、肥胖、运动等都是糖尿病发病的重要因素。近年来,越来越多的研究显示,人体肠道菌群与2型糖尿病、肥胖等代谢性疾病的发生发展密切相关。现就下列问题做一综述:菌群失调与肥胖和胰岛素抵抗,肠道菌群与内毒素、禁食诱导脂肪因子和胆汁酸代谢等。     

基于肠道菌群发现用于治疗Treg缺失免疫缺陷病的新药

目的肠道菌群紊乱与机体多种免疫失衡疾病的发生密切相关,如自身免疫性疾病、肿瘤和代谢综合征等。正是由于肠道菌群的稳定对人体健康至关重要,因此肠道微生态药物已经成为了现在研究与发展的热门产业。本研究挖掘肠道菌群及其代谢产物,发现可用于治疗Treg缺失免疫缺陷病的益生菌和天然产物。方法利用16S r DNA测序技术对Treg缺失介导的自身免疫性疾病模型小鼠的肠道菌群进行检测;用代谢组学技术检测模型小鼠肠道菌群代谢组谱的变化;用分子生物学、基因敲除小鼠等研究益生菌和代谢物作用的分子机制。结果在Treg缺失介导的免疫缺陷病模型小鼠上,肠道菌群发生了严重的紊乱。根据肠道菌群和代谢组谱的变化,选择罗伊氏乳酸杆菌(L. reuteri)和代谢产物肌苷处理Treg缺失小鼠,L. reuteri和肌苷通过激活腺苷受体A2AR抑制了Treg缺失引起的自身免疫性疾病。结论肠道菌群含有大量的微生物以及产生的许多独特代谢产物,可以作为新型天然药物的重要源泉,用于发现治疗自身免疫性疾病、肿瘤等疾病的新型益生菌和活性天然产物。     

糖尿病治疗药物调控肠道微生态及肠降糖激素的研究状况

糖尿病一种以血糖升高、胰岛功能降低为主要特征的慢性代谢性疾病.肠道微生态系统参与调节食物及药物的吸收、分布、代谢和排泄过程.在糖尿病的发病进程中,也常常伴随着肠道微环境和肠降糖激素分泌的改变.本文首先根据作用机制与特点的不同,对现已上市的糖尿病治疗药物进行分类汇总.其次阐述肠道菌群和肠降糖激素与糖尿病病理进程的相关性研...     

肠道菌群通过腺苷A2A受体介导Treg缺失免疫缺陷病

目的阐明肠道菌群在Treg缺失免疫缺陷病的功能和分子机制。方法首先,利用16S r DNA测序技术检测Treg缺失免疫缺陷病模型小鼠的肠道菌群变化;然后,用代谢组学技术检测模型小鼠肠道菌群代谢产物变化,并找出疾病相关的代谢产物;最后,用各种分子生物学、基因敲除小鼠等技术研究分子机理。结果在Treg缺失免疫缺陷病小鼠上,发现肠道菌群发生了严重的紊乱。根据肠道菌群的变化,选择罗伊氏乳酸杆菌(Lactobacillus reuteri,L. reuteri)处理Treg缺失免疫缺陷病小鼠,L. reuteri抑制了Treg缺失引起的自身免疫性疾病。然后,通过代谢组学发现,代谢产物肌苷在罗伊氏乳酸杆菌处理的Treg缺失小鼠上被明显增加。最后,进一步证明罗伊氏乳酸杆菌和肌苷通过激活腺苷A2A受体改善了Treg缺失引起的自身免疫性疾病。结论"肠道菌群-肌苷-A2A受体"轴在Treg缺失免疫缺陷病发生发展中起到非常重要的作用。罗伊氏乳酸杆菌、肌苷以及其他的A2A受体激动剂也许可用于治疗Treg缺失免疫缺陷病。     

肠道菌群与疾病的关系

人类体内的肠道菌群与某些疾病的发生、发展有着重要的关联。研究表明肠道菌群不仅与肠癌、胃癌、肝癌和乳腺癌等癌症的发病有关,还与肥胖症和糖尿病的发病有着密切的关联。肥胖症和糖尿病均属于代谢性疾病,并伴有持续低度炎症。肠道菌群参与机体的能量代谢和储存,菌群失调产生内毒素引发机体炎症等,因此,肠道菌群从多方面参与肥胖症和糖尿病的病程发展。     

肠道菌群失调与糖尿病相关性的研究进展

糖尿病为常见的慢性代谢性疾病之一,具有明显的遗传易感性。患者长期处于高血糖的状态易并发多系统损伤,有着较高的致残率和病死率,严重威胁到患者的健康。近年来,大量研究表明糖尿病的发生发展与遗传、环境等因素有关之外,还与肠道菌群失调有关。糖尿病患者的肠道菌群有着不同程度的失调,其中厚壁菌门与拟杆菌门的丰度变化尤为显著。肠道菌群失调可通过改变宿主肠黏膜屏障、影响短链脂肪酸合成、胆汁酸代谢异常等机制使患者胰岛素敏感性降低、能量代谢异常最终导致糖尿病。基于肠道菌群治疗糖尿病也是目前内分泌领域研究热点,用益生菌、粪便菌群移植、减肥手术等方式均能调节肠道菌群,对糖尿病起到治疗效果,为糖尿病患者带来了新的希望。     

肠道菌群与降糖药物的关系

肠道菌群是寄生于人体肠道内微生物群落的总称,肠道菌群目前已成为医学界热门的课题。近年来全球2型糖尿病患病率逐年攀升,口服降糖药物是常用的治疗方法。有证据表明,口服降糖药物可能会改变肠道微生物组,从而改变胃肠道代谢物以改善宿主健康。尽管肠道菌群、菌群代谢物和2型糖尿病之间的联系很复杂,但了解降糖药物与肠道菌群的关系,对于优化治疗至关重要,对2型糖尿病中益生菌治疗和肠道菌群移植具有指导意义,现就肠道菌群与降糖药物之间的关系做一综述。     

肠道菌群失调与结肠癌发生发展之间关系的研究进展

肠道菌群是机体重要的组成部分,正常状况下肠道菌群保持稳态,在促进营养物质消化吸收、维持肠道正常生理功能、调节机体免疫等众多生命活动中发挥重要的作用。但当体内外环境发生改变,如年龄、饮食习惯、肥胖等代谢性疾病以及抗生素等药物均会造成菌群失调。近年来,很多研究发现肠道菌群失调可以引发多种疾病,其中结肠癌的发生、发展与肠道菌群失调关系密切。同时,有研究资料表明,通过改善肠道菌群的失调状态可降低结肠癌的发生率和抑制结肠癌的生长恶化,但是具体的作用机制尚无清晰的认识。该文就近年来国内外关于肠道菌群失调与结肠癌发生、发展研究的有关热点问题及治疗进行概述,为肠道菌群研究和结肠癌的治疗提供理论参考。     

基于肠道微生物及其代谢产物的2型糖尿病治疗药物的研究进展

随着人类微生物组学研究的深入,肠道微生物在人类健康中的作用逐渐得到重视.作为人体内的隐形器官,肠道微生物参与机体的代谢调控,肠道微生物失调可能造成各种常见代谢紊乱疾病,如2型糖尿病等.通过微生物组学和代谢组学的联合分析,人们逐渐从机制上了解肠道微生物及其代谢衍生物与2型糖尿病的关系.与正常人群相比,2型糖尿病人群中肠道...     

Relationships between intestinal microbiota and Alzheimer disease and regulation of microbiota on prevention and treatment of Alzheimer disease: Review北大核心CSCD

With the extension of human life, the number of patients with Alzheimer disease (AD) is increaseing. However, the mechanisms of AD are still not very clear and there is no effective prevention and treatment process for this disease. In recent years, the importance of intestinal microbiota in the health field has been gradually elaborated, which has become a new research area for AD. There is chronic inflammation, a low level of neurotransmitter 5-hydroxy tryptamine and neurotrophic factor in the central nervous system of AD patients, and a changed structure of AD intestinal microbiota. The intestinal microbiota can cause chronic inflammation, produce neurotoxic substances, and may be related to obesity, type 2 diabetes and other metabolic diseases which are AD high-risk disease, suggesting the correlation between AD and intestinal microbiota. Intestinal microbiota can be regulated by probiotics, prebiotics and traditional Chinese materia medica and beneficial microbiota can reduce inflammation and the occurrence of metabolic syndrome such as diabetes, increase the level of brain neurotransmitter 5-hydroxytryptamine and neurotrophic factor and improve cognitive function. Intestinal microbiota regulation may become a new approach to the prevention and treatment of AD.     

Gut microbiota in pancreatic diseases: possible new therapeutic strategies

Pancreatic diseases such as pancreatitis, type 1 diabetes and pancreatic cancer impose substantial health-care costs and contribute to marked morbidity and mortality. Recent studies have suggested a link between gut microbiota dysbiosis and pancreatic diseases; however, the potential roles and mechanisms of action of gut microbiota in pancreatic diseases remain to be fully elucidated. In this review, we summarize the evidence that supports relationship between alterations of gut microbiota and development of pancreatic diseases, and discuss the potential molecular mechanisms of gut microbiota dysbiosis in the pathogenesis of pancreatic diseases. We also propose current strategies toward gut microbiota to advance a developing research field that has clinical potential to reduce the cost of pancreatic diseases.     

Obesity and diabetes gene discovery approaches

New treatments are currently required for the common metabolic diseases obesity and type 2 diabetes. The identification of physiological and biochemical factors that underlie the metabolic disturbances observed in obesity and type 2 diabetes is a key step in developing better therapeutic outcomes. The discovery of new genes and pathways involved in the pathogenesis of these diseases is critical to this process, however identification of genes that contribute to the risk of developing these diseases represents a significant challenge as obesity and type 2 diabetes are complex diseases with many genetic and environmental causes. A number of diverse approaches have been used to discover and validate potential new targets for obesity and diabetes. To date, DNA-based approaches using candidate gene and genome-wide linkage analysis have had limited success in identifying genomic regions or genes involved in the development of these diseases. Recent advances in the ability to evaluate linkage analysis data from large family pedigrees using variance components based linkage analysis show great promise in robustly identifying genomic regions associated with the development of obesity and diabetes. RNA-based technologies such as cDNA microarrays have identified many genes differentially expressed in tissues of healthy and diseased subjects. Using a combined approach, we are endeavouring to focus attention on differentially expressed genes located in chromosomal regions previously linked with obesity and/or diabetes. Using this strategy, we have identified Beacon as a potential new target for obesity and diabetes.     

他汀类药物对糖尿病的非降脂作用及机制

他汀类药物是胆固醇合成的限速酶3羟基-3甲基戊二酰辅酶A的抑制剂。由于胆固醇堆积与动脉粥样硬化等心血管疾病紧密相关,而2型糖尿病患者也常伴有高胆固醇血症,因此他汀类药物被作为冠心病二级预防和改善糖尿病脂质紊乱的一线用药。近年的临床和基础研究证明,他汀类药物除了降脂作用外,还有改善胰岛素敏感性、胰岛β细胞功能和糖代谢,减轻糖尿病并发症和炎症的作用。也有不少相关不良反应的报道,但作用机制尚不明了。研究和探讨他汀类药物在糖尿病防治中的降脂外作用和机制,将有利于这类药物的合理应用。文中主要介绍他汀类药物对糖尿病的非降脂作用及可能机制。     

Next generation probiotics in disease amelioration

Studies on the role of gut commensal bacteria in health development have rapidly attracted much more attention beyond the classical pathogens over the last decade. Many important reports have highlighted the changes in the gut microbiota (dysbiosis) are closely related to development of intra- and extra-intestinal, chronic inflammation related diseases such as colitis, obesity/metabolic syndromes, diabetes mellitus, liver diseases, cardiovascular diseases and also cancer and neurodegenerative diseases. To circumvent these difficulties, the strategy of modulating the structure of the gut microbiota has been under intensive study and shed more light on amelioration of these inflammation related diseases. While traditional probiotics generally show marginal ameliorative effects, emerging next generation probiotics start to reveal as new preventive and therapeutic tools. Recent studies have unraveled many potential next generation probiotics (NGP). These include Prevotella copri and Christensenella minuta that control insulin resistance, Parabacteroides goldsteinii, Akkermansia muciniphila and Bacteroides thetaiotaomicron that reverse obesity and insulin resistance, Faecalibacterium prausnitzii that protects mice against intestinal diseases, and Bacteroides fragilis that reduces inflammation and shows anticancer effect. New agents will soon be revealed for targeted therapy on specific inflammation related diseases. The important roles of next generation probiotics and gut microbiota normobiosis on the maintenance of intestinal integrity and homeostasis are emphasized.     

肠道菌群对某些疾病及药物疗效与毒性的影响

经过长期的协同进化,肠道菌群与宿主间形成了密切的共生关系,并对宿主的多种生理功能起着重要作用。在相关疾病的治疗过程中,药物对肠道菌群的影响以及肠道菌群对药物和疾病的影响相互交织,并有可能改变药物在体内的药动学过程及药效。综述药物、肠道菌群以及疾病三者间的相互作用与联系,提出利用药物调节肠道菌群以治疗相关疾病的思路,为现有药物的新药理作用的发现和以肠道菌群为作用靶点的新型药物的研发提供有益信息。     

Effects of clovamide and its related compounds on the aggregations of amyloid polypeptides

Journal of Natural Medicines - Alzheimer's disease (AD) and type 2 diabetes (T2D) are common diseases in the elderly, and the increasing number of patients with these diseases has become a...     

2型糖尿病患者胰岛素用量及其影响因素分析

目的探讨影响2型糖尿病患者胰岛素用及其影响因素。方法回顾分析96例住院2型糖尿病记录患者的性别、年龄、身高、体重、病程、达标时胰岛素用量等,测定糖化血红蛋白（HbAlc）、空腹血糖（FPG）、空腹胰岛素（Ins）、餐后2小时Ins、甘油三酯（TG）、总胆固醇（TC）和低密度脂蛋白胆同醇（LDL—c）水平等指标。结果2型糖尿病胰岛素治疗用量达标时与体重、空腹Ins、空腹血糖、TG、病程有关,五个变量的标准回归系数分别为0．668、0．443、0．405、0．306、0．160,P值分别为0．000、0．000、0．001、0．006、0．020。结论体重、空腹Ins、空腹血糖、TG、病程者将影响2型糖尿病患者胰岛素用量。