高原肠道菌群与癫痫的研究进展

肠道菌群作为人体内重要的微生态系统,可通过肠-脑轴与中枢神经系统产生多途径双向联系,对大脑的生理、认知功能进行调控。在高原低压缺氧的环境下,肠道微生态失调致肠道菌群的组成及功能可能有不同程度的改变,菌群失调可引起神经免疫炎症、血-脑脊液屏障功能障碍、神经递质失衡对癫痫的诱发和发展起着重要作用。本文就高原肠道菌群对癫痫易感性的影响进行综述,以加深肠道菌群在癫痫治疗方面的认识,为癫痫治疗提供新的思路。     

血管性痴呆与肠道菌群的相关研究进展

血管性痴呆是一种常见的痴呆类型,与脑血管疾病密切相关,主要表现为认知功能下降.神经炎症对血管性痴呆有重要影响.肠道菌群可通过调控神经递质和肠道代谢产物调节血管性痴呆的神经炎症;肠道菌群组成异常也会增加肠道屏障的通透性,激活机体免疫系统引发全身炎症反应,进而破坏血脑屏障,加重神经炎症,导致神经细胞凋亡,发生神经退行性病变...     

肠道菌群与双相障碍发病机制相关研究进展

双相障碍是世界范围内导致经济负担和残疾的主要原因,但其潜在机制仍没有得到充分说明,治疗效果欠佳,易复发.近年来,肠道菌群在双相障碍中的作用越来越受到关注.双相障碍患者的肠道菌群发生变化,且其可通过免疫炎症反应、神经内分泌和神经系统等多种途径与大脑进行双向信息交流,引起情绪、精力水平和行为变化.因此,本文就肠道菌群与双相...     

肠道菌群与神经免疫系统及神经退行性疾病的相关研究进展

神经退行性疾病包括阿尔茨海默病、帕金森病等,严重影响患者的生存质量.肠道菌群参与神经退行性疾病的发生发展.其中,菌-肠-脑轴是肠道菌群影响神经退行性疾病的重要途径.而肠道菌群也是神经免疫系统发育和发挥作用的关键因素.作为一条双向通道,菌-肠-脑轴主要通过神经免疫系统等方式连接肠道菌群与大脑,且神经退行性疾病可能起源于肠...     

肠道菌群和癫痫相关性研究进展

肠道微生物对维持人类正常的生理功能具有重要意义,正常的肠道菌群在宿主营养代谢、药物代谢、维持肠道黏膜屏障结构完整、免疫调节和抵御病原体等方面发挥重要作用。肠道菌群不仅通过神经系统,而且通过内分泌系统、免疫系统和代谢系统对大脑产生影响,这种肠道和大脑之间的双向通信称之为脑-肠轴。人体内存在的脑-肠轴可能是大脑和胃肠道之间关键调控通路,而肠道菌群为该通路的重要参与者,肠道微生物群的变化可通过免疫机制作用于中枢和周围神经系统,导致脑功能改变,从而参与了帕金森氏病、老年痴呆症、精神分裂症和多发性硬化症等多种中枢神经系统疾病的发病机制。癫痫是一种以具有持久性的致痫倾向为特征的慢性脑部疾病,免疫机制在癫痫尤其是免疫性癫痫的发生和发展中发挥了重要作用。免疫性癫痫是免疫介导以反复或持续性癫痫发作为主要临床表现的疾病,其特征为频繁的局灶性癫痫发作、脑病、进行性认知障碍、局灶性神经功能受损或伴发其他中枢神经系统缺陷。机体免疫反应的异常激活(包括固有免疫和后天获得性免疫)参与了免疫性癫痫的发病机制,患者脑脊液中可检测到神经元特异性相关抗体具有诊断意义。临床上抗炎或免疫治疗在某些药物难治性癫痫,尤其是诊断明确的免疫性癫痫可能具有良好的治疗作用,通过免疫调控和肠道菌群重建可能是未来治疗自身免疫性癫痫的重要途径。      

重度抑郁症与肠道菌群关系的研究进展

重度抑郁症是高度异质性的精神疾病,具有复杂的病理生理,发病机制尚不明确.遗传倾向、环境因素以及生物系统在重度抑郁症的发病中起作用.肠道菌群作为胃肠道生态系统共生的微生物,可通过肠-脑轴双向交流信息系统与宿主相互作用.肠道菌群失调可能与重度抑郁症的发病相关.本文就肠道菌群与重度抑郁症的关系及在重度抑郁症治疗中作用研究进展...     

肠道菌群和缺血性脑卒中的研究进展

肠道菌群被誉为人类的第二基因组,已经成为众多研究的热点。这些高度多样化、数量庞大的肠道菌群对人类的健康至关重要。肠道菌群参与许多重要的生理功能,如食物的消化和新陈代谢、免疫反应以及炎症等。缺血性脑卒中是一种常见的脑血管疾病,具有高发病率、高致残率和高病死率的特点。有研究表明肠道菌群与中枢神经系统疾病的发生发展有着密切关系,尤其是缺血性脑卒中,研究肠道菌群与缺血性脑卒中的相关性,可为缺血性脑卒中的预防和治疗提供新的途径。     

高蛋白饮食通过调控肠道菌群影响肥胖相关研究进展

肠道菌群与肥胖症的发生、发展密切相关,饮食模式可通过影响宿主的肠道菌群参与机体能量代谢,进而发挥减重作用。高蛋白饮食不仅能改变肠道菌群的组成结构与肠道微生态的多样性,在肠道内还可被菌群进一步分解产生色氨酸、吲哚、5-羟色胺等一系列代谢产物,对人体的脑-肠轴及肠道黏膜免疫发挥调控作用,可有效降低肥胖患者体重,并改善机体的慢性低度炎症与代谢状态,为肥胖症的防治提供新的思路。     

肠道菌群介导的阿尔茨海默病炎症途径的研究进展

阿尔茨海默病(Alzheimer′s disease, AD)是一种神经退行性疾病,是痴呆中最常见的类型。该疾病以记忆和认知能力的逐渐丧失为特征,严重威胁着人类健康和生活质量。近年来,神经炎性反应在AD中的作用受到日益关注和研究,被认为是AD的主要发病机制。而肠道菌群和大脑之间的双向交流也是近年来研究的重大发现。它可以通过肠-脑轴调节宿主大脑功能和行为,从而改变宿主患病的风险,与神经退行性疾病密切相关。现有研究发现肠道菌群可以通过多种途径诱发机体炎性反应,进而导致AD的发生。本文对肠道菌群诱发炎症导致AD的研究进展进行综述,为深入认识肠道菌群对AD的影响及其调控提供新途径。     

肠道菌群与抑郁症关系的研究进展

人体的肠道菌群是一个数量巨大的动态种群合集,且在每个个体中都是独一无二的。肠道菌群的定植从怀孕期间开始,分娩后受药物、饮食和压力等因素影响形成了个体的菌群差异,并随着时间推移大多数菌群结构保持稳定。随着对肠道菌群研究的不断深入,越来越多的证据显示:肠道菌群与抑郁障碍有密切关联,该关联源于肠道和大脑之间的双向通信系统,称为肠道菌群-肠道-脑(MGB)轴,MGB轴在维持大脑和肠道的正常功能中发挥着重要作用,其作用机制可能涉及下丘脑-垂体-肾上腺(HPA)轴、中枢神经系统、肠神经系统、免疫系统、神经递质、神经调节物质、肠黏膜屏障和血脑屏障途径。基于肠道菌群与抑郁症的密切关系,如何逆转肠道菌群失调成为目前研究的重点。肠道菌群干预治疗,即通过益生元、益生菌和粪菌移植(FMT)等方法来改善肠道菌群状态,可能为抑郁症提供一种有前景的治疗方法。现对肠道菌群与抑郁症之间的相互影响、肠道菌群失调在抑郁症发病中的可能机制和肠道菌群干预治疗抑郁症的初步尝试进行全面综述,旨在更好地了解肠道菌群与抑郁症的关系,为探索抑郁症的防治提供新靶点和新思路。     

肠道菌群对免疫系统影响的研究进展

【摘要】〓肠道菌群是机体的重要组成部分,与免疫系统的关系十分密切。肠道微生物可以对免疫系统,包括全身性的固有免疫、特异性免疫甚至自身免疫疾病产生影响。来自于机体内外的理化刺激和生物刺激会打破正常菌群与人体之间的动态平衡,菌群数量和种类的改变都会导致肠道内菌群的紊乱,多项研究表明,肠道菌群紊乱可能在多种免疫疾病的形成中起着重要作用。     

抑郁症肠道微生物组紊乱假说的现状与展望

抑郁症是一种基因与环境交互影响的重大精神疾病。其发病机制学说众多,但仍未获得广泛认同。肠道微生物是人体最大、最直接的外环境,已成为解析抑郁症的全新切入点。根据最新研究进展,本文将从以下几个方面来进行综述：（1）肠道微生物通过"微生物-肠-脑"轴影响脑神经生化和行为表型;（2）肠道微生物紊乱与抑郁发生的相关性;（3）肠道微生物在抑郁发生中的潜在致病机制;（4）展望以抑郁症肠道微生物紊乱为靶点,开发抑郁症新的诊治方法。     

无菌动物在饮食干涉肠道菌群研究中的应用

膳食干涉对肠道菌群与健康的影响已成为医学健康领域的研究热点,从发展来看,肠道菌群有可能会成为研究饮食方式、保健食品、中药制剂等对人体健康影响的重要靶标。然而,肠道菌群由于其复杂性,研究它和饮食干涉的关系对动物模型有高标准的要求,无菌动物体内外不携带任何活的微生物和寄生虫,在生物医学及人体疾病和健康等方面均有一定的应用和研究,是当前肠道菌群研究中应用最多的基础动物模型。采用无菌动物构建人源菌群动物是研究饮食、菌群与健康关系的常用方式。本文主要综述无菌动物构建人源菌群动物的研究应用及饮食干涉对肠道菌群的影响。     

肠道微生物紊乱诱导抑郁的肠-脑分子机制研究

抑郁症(major depressive disorder,MDD)是一种严重影响人类健康的重大精神疾病。越来越多的研究显示肠道微生物紊乱在MDD发病过程中具有重要调节作用。本课题组针对MDD存在的肠道微生物紊乱、引起MDD发病的关键肠道微生物、肠道微生物紊乱诱发MDD的肠-脑分子机制开展了系列研究,本文就课题组已取得的研究进展作一综述。     

间歇性缺氧对睡眠呼吸暂停大鼠模型肠道菌群结构的影响

目的 探讨间歇性缺氧(IH)对睡眠呼吸暂停综合征(OSAS)大鼠模型肠道菌群结构的影响。方法 16只大鼠随机均分为两组,分别给予4周常氧处理(NC组)或间歇性缺氧处理(IH组)。然后采集并提取大鼠粪便DNA,进行16S rRNA焦磷酸测序,并对测序结果进行生物信息学分析。Welch T检验分析两组间样本α多样性差异,ANOSIM分析检验组间β多样性差异,KW秩和检验分析组间显著丰度差异。结果 IH组与NC组间OTUs数量无显著差异(P＞0.05)。且群落多样性(Shannon指数)和丰富度(Chao1指数)亦无显著差异(P＞0.05)。物种差异分析显示,在门水平,拟杆菌门(P＜0.05)、软壁菌门(P＜0.01)在IH组肠道中显著富集,而厚壁菌门(P＜0.05)在NC组肠道中显著富集,但并未发现IH对大鼠肠道内变形菌门(P＞0.05)物种丰度的影响。在科水平上,优势菌科中,普雷沃氏菌科(P＜0.05),克里斯滕森菌科(P＜0.001),韦荣球菌科(P＜0.05),柔膜细菌RF9(P＜0.01)在IH组显著富集,理研菌科(P＜0.001),乳杆菌科(P＜0.01)在NC组显著富集。弱势菌科中,产碱菌科(P＜0.01),红螺菌科(P＜0.05),vadinBE97(P＜0.05)IH组显著富集。网络分析显示,IH组和NC组间有广泛的物种之间的相互作用。结论 间歇性缺氧可以显著改变大鼠肠道菌群结构特征。     

Transformation of berberine to its demethylated metabolites by the CYP51 enzyme in the gut microbiota

Berberine (BBR) is an isoquinoline alkaloid extracted from Coptis chinensis that improves diabetes, hyperlipidemia and inflammation. Due to the low oral bioavailability of BBR, its mechanism of action is closely related to the gut microbiota. This study focused on the CYP51 enzyme of intestinal bacteria to elucidate a new mechanism of BBR transformation by demethylation in the gut microbiota through multiple analytical techniques. First, the docking of BBR and CYP51 was performed; then, the pharmacokinetics of BBR was determined in ICR mice in vivo, and the metabolism of BBR in the liver, kidney, gut microbiota and single bacterial strains was examined in vitro. Moreover, 16S rRNA analysis of ICR mouse feces indicated the relationship between BBR and the gut microbiota. Finally, recombinant E. coli containing cyp51 gene was constructed and the CYP51 enzyme lysate was induced to express. The metabolic characteristics of BBR were analyzed in the CYP51 enzyme lysate system. The results showed that CYP51 in the gut microbiota could bind stably with BBR, and the addition of voriconazole (a specific inhibitor of CYP51) slowed down the metabolism of BBR, which prevented the production of the demethylated metabolites thalifendine and berberrubine. This study demonstrated that CYP51 promoted the demethylation of BBR and enhanced its intestinal absorption, providing a new method for studying the metabolic transformation mechanism of isoquinoline alkaloids in vivo.     

Features of gut microbiota in patients with anorexia nervosa

Background:Anorexia nervosa (AN) is a psychological disorder, which is characterized by the misunderstanding of body image, food restriction, and low body weight. An increasing number of studies have reported that the pathophysiological mechanism of AN might be associated with the dysbiosis of gut microbiota. The purpose of our study was to explore the features of gut microbiota in patients with AN, hoping to provide valuable information on its pathogenesis and treatment.Methods:In this cross-sectional study, from August 2020 to June 2021, patients with AN who were admitted into Peking University Third Hospital and Peking University Sixth Hospital (n = 30) were recruited as the AN group, and healthy controls (HC) were recruited from a middle school and a university in Beijing (n = 30). Demographic data, Hamilton Depression Scale (HAMD) scores of the two groups, and length of stay of the AN group were recorded. Microbial diversity analysis of gut microbiota in stool samples from the two groups was analyzed by 16S ribosomal RNA (rRNA) gene sequencing.Results:The weight (AN vs. HC, [39.31 ± 7.90] kg vs. [56.47 ± 8.88] kg, P < 0.001) and body mass index (BMI, AN vs. HC, [14.92 ± 2.54] kg/m²vs. [20.89 ± 2.14] kg/m², P < 0.001) of patients with AN were statistically significantly lower than those of HC, and HAMD scores in AN group were statistically significantly higher than those of HC. For alpha diversity, there were no statistically significant differences between the two groups; for beta diversity, the two groups differed obviously regarding community composition. Compared to HC, the proportion of Lachnospiraceae in patients with AN was statistically significantly higher (AN vs. HC, 40.50% vs. 31.21%, Z = −1.981, P = 0.048), while that of Ruminococcaceae was lower (AN vs. HC, 12.17% vs. 19.15%, Z = −2.728, P = 0.007); the proportion of Faecalibacterium (AN vs. HC, 3.97% vs. 9.40%, Z = −3.638, P < 0.001) and Subdoligranulum (AN vs. HC, 4.60% vs. 7.02%, Z = −2.369, P = 0.018) were statistically significantly lower, while that of Eubacterium_hallii_group was significantly higher (AN vs. HC, 7.63% vs. 3.43%, Z = −2.115, P = 0.035). Linear discriminant effect (LEfSe) analysis (LDA score >3.5) showed that o_Lachnospirales, f_Lachnospiraceae, and g_Eubacterium_hallii_group (o, f and g represents order, family and genus respectively) were enriched in patients with AN. Microbial function of nutrient transport and metabolism in AN group were more abundant (P > 0.05). In AN group, weight and BMI were significantly negatively correlated with the abundance of Bacteroidota and Bacteroides, while positively correlated with Subdoligranulum. BMI was significantly positively correlated with Firmicutes; HAMD scores were significantly negatively correlated with Faecalibacterium.Conclusions:The composition of gut microbiota in patients with AN was different from that of healthy people. Clinical indicators have correlations with the abundance of gut microbiota in patients with AN.     

BMPs 在中枢神经系统发育和神经保护中的作用

骨形态发生蛋白（Bone morphogenetic proteins,BMPs）是转化生长因子-β（transforming growth factor -β）超家族的成员,现已经发现 BMPs 很多亚型 BMP 分子在神经系统的不同区域呈持续性表达,但是表达在空间和时间具有差异性,提示不同亚型 BMPs 的功能在神经系统也存在差异。本文主要就 BMPs 在中枢神经系统发育中的作用和神经保护功能作一综述。     

Interactions between gut microbiota and berberine,a necessary procedure to understand the mechanisms of berberine

Berberine (BBR), an isoquinoline alkaloid, has been found in many plants, such as Coptis chinensis Franch and Phellodendron chinense Schneid. Although BBR has a wide spectrum of pharmacological effects, its oral bioavailability is extremely low. In recent years, gut microbiota has emerged as a cynosure to understand the mechanisms of action of herbal compounds. Numerous studies have demonstrated that due to its low bioavailability, BBR can interact with the gut microbiota, thereby exhibiting altered pharmacological effects. However, no systematic and comprehensive review has summarized these interactions and their corresponding influences on pharmacological effects. Here, we describe the direct interactive relationships between BBR and gut microbiota, including regulation of gut microbiota composition and metabolism by BBR and metabolization of BBR by gut microbiota. In addition, the complex interactions between gut microbiota and BBR as well as the side effects and personalized use of BBR are discussed. Furthermore, we provide our viewpoint on future research directions regarding BBR and gut microbiota. This review not only helps to explain the mechanisms underlying BBR activity but also provides support for the rational use of BBR in clinical practice.     

老年性功能性便秘与肠道菌群及代谢产物的关系

<正>老年性功能性便秘(functional constipation in the elderly,FCE)是一种临床上常见的肠道疾病。全球数据^[1-2]显示,功能性便秘(functional constipation,FC)的平均发病率约为14.0%,而中国部分东部城市FCE患病率高达17.6%。有研究^[3]指出,FCE与多种严重疾病相关,包括结直肠癌、肝性脑病、阿尔兹海默病等,可能导致急性心肌梗死和脑血管意外等,从而增加患者的死亡风险,为社会带来了沉重的医疗负担。FCE的发病机制至今尚未完全明确,与肠道动力学障碍、精神心理状态异常、肠道菌群及其代谢产物等多方面因素有关,其特点是无器质性病变。近年来,肠道菌群及其代谢产物在FCE中的作用受到越来越多的关注,被认为是FCE主要的病因之一^[4]。本文旨在简要综述FCE与肠道菌群及代谢产物之间的关系。