江苏无锡健康与肠病人群肠道脱硫弧菌数量及肠道菌群多样性

[目的]研究息肉、溃疡性结肠炎、直肠结肠癌和健康人群肠道中脱硫弧菌数量的差异,及不同人群肠道菌群的多样性,分析脱硫弧菌数量及肠道菌群多样性与肠道疾病之间的潜在关系.[方法]采用实时荧光定量PCR(RT-PCR)的方法,对58名受试者肠道脱硫弧菌的数量进行定量分析.采用PCR-DGGE技术,对不同人群的肠道脱硫弧菌和肠道菌群结构进行分析,结合16S rRNA V3区测序分析不同人群肠道菌群多样性的差异.[结果]RT-PCR分析显示,所有受试者均为脱硫弧菌阳性,其中息肉(2.9×106cfu/mL)和溃疡性结肠炎人群(1.2×106 cfu/mL)肠道中脱硫弧菌的数量明显高于健康人群(7.0×105 cfu/mL),直肠结肠癌人群(6.8×105 cfu/mL)肠道中脱硫弧菌的数量与健康人群无明显差异.DGGE图谱聚类分析结果表明,肠道疾病人群肠道中脱硫弧菌的菌群相似度较高,而与健康人群之间的差异较大.16S rRNA V3区基因测序显示肠道疾病人群与健康人群在肠道菌群多样性和优势菌群方面均有明显差异.[结论]通过RT-PCR与DGGE相结合的方法,说明肠道脱硫弧菌数量的增多是息肉和溃疡性结肠炎疾病的一个重要特征,且其菌群组成在肠道疾病人群与健康人群之间存在明显差异.与健康人群相比,肠道疾病人群的肠道微生物多样性升高,优势菌群发生偏移,菌群失衡.     

甘肃省武威市胃癌患者肠道菌群分布

目的 通过比较甘肃省武威市胃癌患者和健康对照人群肠道菌群的分布,探讨胃癌患者肠道菌群的变化与胃癌发生发展的关系,并寻找可能作为该地区胃癌患者的潜在生物标志物.方法 收集24例胃癌患者和24例健康对照人群的粪便样本,提取DNA,采用16S rRNA基因高通量测序进行肠道菌群分析.结果 分析2组研究对象肠道菌群的Alpha...     

1 067例不同年龄及地域人群肠道菌群特征

目的 探索不同人群在不同年龄阶段的菌群结构特点,了解环境因素对肠道菌群组成及发展的影响。方法 收集65例中国健康儿童粪便样本并进行16S rRNA检测,同时从已发表文献中获取来自亚洲、非洲、欧洲、北美洲及南美洲国家的1 002例健康人群肠道菌群数据,分析来自不同年龄阶段健康人群肠道菌群的特征。结果 3岁以下全球各地儿童肠道菌群的种类较为一致：拟杆菌属和双歧杆菌属在儿童肠道菌群中占据主导地位,且它们在免疫调节上有重要作用。3岁以上健康人群的肠道菌群则展示出了地域性特征：亚洲健康人群的肠道代表菌属为考拉杆菌属和巨单胞菌属,非洲健康人群的肠道代表菌属为粪杆菌属,欧洲健康人群的肠道代表菌属也是粪杆菌属,北美洲健康人群的肠道代表菌属为拟杆菌属,南美洲健康人群的肠道代表菌属为普氏菌属。另外,经济较发达的欧洲及北美洲健康人群的肠道菌群多样性显著高于其他经济较落后地区。结论 本研究加深了对不同地域人群肠道菌群特点以及它们随年龄增长而发展变化的认识。     

肺部菌群和肠道菌群及其互作与肺癌发生发展的相关性研究进展

肺部菌群及肠道菌群与肺癌密切相关,研究发现与健康人群相比肺癌患者的肺部及肠道菌群发生失调,即菌群组成结构发生显著改变。随着“肠-肺轴”概念的提出,肺部及肠道菌群在人体内的紧密联系越发受到重视,因此关于肺部及肠道菌群的研究对于阐明肺癌的发生发展机制有重要的指引作用。文中综述了肺癌患者肺部及肠道菌群的组成特点及可能的互作机制,强调了肠-肺轴中免疫系统的重要性,最后总结了肺部及肠道菌群对肺癌临床治疗的影响,并对肺部及肠道菌群可作为肺癌早期诊断与治疗的新颖靶点进行了展望。     

赫哲族和汉族健康人群肠道细菌群落分析

目的 对汉族和赫哲族健康人群肠道菌群进行研究,探讨遗传背景和饮食习惯对肠道菌群多样性以及组成的影响.方法 以佳木斯市区20例健康汉族人群、佳木斯街津口赫哲族聚居地的20例健康赫哲族志愿者及20例健康汉族人群粪便样本为研究对象,应用基于16S rDNA V3-V4可变区的高通量测序技术测定肠道菌群多样性以及核心菌群的组成...     

双歧杆菌低聚果糖制剂对便秘人群肠道菌群的调整作用

目的调查便秘与非便秘人群肠道菌群状况,考察便秘人群服用双歧杆菌低聚果糖合生元后肠道菌群改善的情况。方法采集40岁以上便秘与非便秘人群粪便,各选取10例作厌氧和需氧菌培养、计数与鉴定。结果分离培养出葡萄球菌、肠杆菌、酵母菌、双歧杆菌和乳酸杆菌。比较不同组人群5种肠道菌群的差异,结果显示便秘人群中出现肠道菌群失调,便秘组双歧杆菌、乳杆菌含量明显降低,服用双歧杆菌低聚果糖合生元后肠道菌群状况恢复到正常人群水平。结论服用双歧杆菌低聚果糖合生元可以改善便秘人群肠道菌群失调状况,对便秘人群具有一定治疗作用。     

肠道菌群与宿主关系解析及肠道菌群调控/合成研究进展

肠道菌群和宿主健康之间有着密切的关系,其与宿主之间存在着复杂的相互作用,如菌群及其代谢产物与免疫系统的互作、脑-肠轴、肺-肠轴等.肠道菌群紊乱与多种疾病的发生和发展存在相关性,且部分微生物菌株与一些疾病的发生存在着因果关系.肠道菌群还会影响药物代谢,个体差异的肠道菌群使得不同个体对于同种药物的代谢具有很大差别;解析个体肠道菌群的状态及其与宿主之间的关系是实施个性化精准诊疗的重要环节.肠道菌群具有可塑性,通过饮食调控、益生菌/益生元/合生元补充、粪菌移植等干预手段可以使肠道菌群处于健康状态,应用肠道菌群编辑和合成肠道微生物组等新技术调控、合成肠道菌群的研究已有报道.目前,利用合成生物学等方法调控肠道菌群已成为改善和治疗疾病的有效方法之一.本文综述了肠道菌群与人体等宿主的相互作用、肠道菌群与部分疾病的相关性和因果性,以及通过肠道菌群调控改善人体健康状态的策略,展望了微生物组学和合成生物学在肠道菌群调控与合成方面的应用.     

肥胖人群肠道菌群特征分析及机器学习模型

【背景】肠道菌群与人体健康之间的关系吸引了越来越多的关注,成为目前热门的研究热点。【目的】基于美国肠道计划公开数据库,对肥胖和健康人群肠道菌群进行比较分析,解析肥胖人群肠道菌群特征,并基于肠道菌群建立机器学习模型预测人群肥胖的状态,为基于肠道菌群干预肥胖提供理论基础。【方法】从公开数据库中获取美国肠道计划中的肠道菌数据,经过筛选得到1 655个健康(18.530)成年人的肠道菌群数据。针对α多样性,进行了Wilcox秩和检验分析并通过Logsitic回归判定α多样性与肥胖之间的关系;对Unweighted UniFrac、WeightedUniFrac和Bray-Curtis三种β多样性距离进行主成分分析(principalcomponent analysis,PCA),探索肥胖与健康人群在肠道菌群组成上的差异;对于物种差异,进行Wilcox秩和检验探索差异菌属;通过PICRUSt分析预测可能的代谢通路,同时与肠道菌群进行相关性分析。利用Scikit-Learn软件包基于属水平的肠道菌群数据建立肥胖分类机器学习模型,并进行网络搜...     

不同身体质量指数人群肠道菌群结构及共存网络解析

[背景] 人体能量稳态失衡表现为体重过轻、超重和肥胖,肠道菌群与人体能量稳态的维持有关,但不同身体质量指数（Body Mass Index,BMI）人群的肠道菌群特征仍需进一步探究。[目的] 基于美国肠道计划公开数据库,解析4类BMI人群肠道菌群的特征,并探究4类BMI人群肠道菌群共存网络特征及差异,为基于肠道菌群来干预肥胖及体重过轻等不健康状态提供新的理论依据。[方法] 从美国肠道计划数据集中筛选具有BMI信息的肠道菌群样本,并根据世界卫生组织规定的BMI划分标准将筛选后的样本分为4类：体重过轻（BMI<18.5 kg/m²）,正常体重（18.5 kg/m²2）,超重（25 kg/m²2）,肥胖（BMI>30 kg/m²）;通过计算和比较肠道菌群的α多样性和β多样性探究4类BMI人群肠道菌群的整体结构特征及差异;通过多元线性回归模型对不同BMI分类与肠道菌群进行相关性分析,并且将地域、年龄、性别因素作为混杂因素加入到模型中进行校正;采用SparCC分别计算4类BMI人群肠道菌群中菌属相关性,并分别构建肠道菌群共存网络。[结果] 经过Wilcoxon秩和检验,发现体重过轻、超重、肥胖人群的肠道菌群α多样性都显著低于正常体重人群;β多样性分析结果表明4类BMI人群肠道菌群的整体结构存在显著差异;4类BMI人群肠道中厚壁菌门（Firmicutes）和拟杆菌门（Bacteroidetes）的相对含量无显著差异;通过MaAsLin分析,并且将地域、年龄、性别因素作为混杂因素加入到模型中进行校正,共得到49个与BMI类型显著相关的物种;4类BMI人群肠道菌群共存网络的拓扑结构具有一定差异,体重过轻和正常体重人群肠道菌群共存网络的复杂度较高,超重和肥胖人群肠道菌群共存网络的复杂度较低。[结论] 4类BMI人群肠道菌群的多样性、整体结构和共存网络间均存在差异。     

益生菌对不同年龄人群功能性便秘治疗效果的研究进展

功能性便秘是一种常见的功能性胃肠道疾病。患者通常伴有腹痛、腹胀等现象,严重影响患者生活质量,其治疗仍具有挑战性。近年来研究发现肠道菌群紊乱与功能性便秘的发生发展密切相关。益生菌能够调节肠道菌群平衡,加强肠道生物的屏障功能,参与免疫系统发挥作用,为治疗功能性便秘提供了新思路。本文对益生菌治疗功能性便秘的现状进行综述,阐明功能性便秘的发生机制、功能性便秘患者的肠道菌群变化及益生菌治疗不同年龄人群功能性便秘的效果,为益生菌在功能性便秘患者中的应用提供参考。     

Current understanding of microbiota- and dietary-therapies for treating inflammatory bowel disease

Inflammatory bowel disease (IBD) is a result of chronic inflammation caused, in some part, by dysbiosis of intestinal microbiota, mainly commensal bacteria. Gut dysbiosis can be caused by multiple factors, including abnormal immune responses which might be related to genetic susceptibility, infection, western dietary habits, and administration of antibiotics. Consequently, the disease itself is characterized as having multiple causes, etiologies, and severities. Recent studies have identified >200 IBD risk loci in the host. It has been postulated that gut microbiota interact with these risk loci resulting in dysbiosis, and this subsequently leads to the development of IBD. Typical gut microbiota in IBD patients are characterized with decrease in species richness and many of the commensal, and beneficial, fecal bacteria such as Firmicutes and Bacteroidetes and an increase or bloom of Proteobacteria. However, at this time, cause and effect relationships have not been rigorously established. While treatments of IBD usually includes medications such as corticosteroids, 5-aminosalicylates, antibiotics, immunomodulators, and anti-TNF agents, restoration of gut dysbiosis seems to be a safer and more sustainable approach. Bacteriotherapies (now called microbiota therapies) and dietary interventions are effective way to modulate gut microbiota. In this review, we summarize factors involved in IBD and studies attempted to treat IBD with probiotics. We also discuss the potential use of microbiota therapies as one promising approach in treating IBD. As therapies based on the modulation of gut microbiota becomes more common, future studies should include individual gut microbiota differences to develop personalized therapy for IBD.     

肝硬化患者肠道菌群失衡的研究现状

肝硬化是我国的一种常见病,近年来越来越多的研究表明肝硬化及其并发症（如门静脉高压、自发性腹膜炎、肝性脑病及肝癌等）都与肠道菌群失衡有着密切的联系。肝脏和肠道通过“肠—肝轴”紧密联系在一起,肝硬化时因小肠细菌过度生长、肠黏膜屏障功能受损、机体免疫功能下降等因素,导致细菌移位、肠道微生态失衡。而肠道微生态失衡又会使肝功能障碍进一步发展,引起肝性脑病等并发症。本文就目前国内外对肝硬化及其并发症与肠道细菌及真菌菌群失衡的研究进行综述。     

化疗对肠道菌群及血清5-羟色胺水平的影响

化疗不仅导致肠黏膜炎和5-羟色胺（5-HT）水平的异常,也会诱发肠道菌群失衡。平衡状态下的微生物是一道生物屏障,菌群失衡可加剧肠道炎症。近期研究发现,5-HT的水平受肠道菌群的调节。因此,化疗引起的5-HT水平改变可能与肠道菌群的异常有关。本研究主要探讨肠道菌群通过何种途径影响化疗后肠黏膜炎和5-HT水平,为临床上以益生菌调节肠道菌群来改善化疗后的胃肠道反应提供依据。     

The role of the microbiome in gastrointestinal inflammation

The microbiome plays an important role in maintaining human health. Despite multiple factors being attributed to the shaping of the human microbiome, extrinsic factors such diet and use of medications including antibiotics appear to dominate. Mucosal surfaces, particularly in the gut, are highly adapted to be able to tolerate a large population of microorganisms whilst still being able to produce a rapid and effective immune response against infection. The intestinal microbiome is not functionally independent from the host mucosa and can, through presentation of microbe-associated molecular patterns (MAMPs) and generation of microbe-derived metabolites, fundamentally influence mucosal barrier integrity and modulate host immunity. In a healthy gut there is an abundance of beneficial bacteria that help to preserve intestinal homoeostasis, promote protective immune responses, and limit excessive inflammation. The importance of the microbiome is further highlighted during dysbiosis where a loss of this finely balanced microbial population can lead to mucosal barrier dysfunction, aberrant immune responses, and chronic inflammation that increases the risk of disease development. Improvements in our understanding of the microbiome are providing opportunities to harness members of a healthy microbiota to help reverse dysbiosis, reduce inflammation, and ultimately prevent disease progression.     

后生元(postbiotics):调节肝硬化患者肠道菌群及疾病进程的新策略

肝硬化是慢性肝炎发展的终末阶段,患者出现有不同程度的肠道菌群失调,并伴有肠道屏障功能的缺失和菌群移位,是引发肝硬化并发症的重要原因。尽管益生菌能在多个层面保护肠道屏障功能,但其在肝硬化肠道菌群紊乱中的疗效并不明确。现在的研究发现一些益生菌的组分或代谢产物有着与益生活菌类似的益生功效,包括稳定肠道菌群、加强肠上皮屏障功能和调节肠黏膜免疫反应等,其重要的优点是具有明确的分子结构和显著的生物活性,可能是未来调节肝硬化肠道菌群及疾病进程的新方向。本文主要总结了肝硬化肠道菌群失调对于肝硬化并发症及疾病进程的影响,探讨了益生菌的作用及局限性,并重点讨论后生元在调控肝硬化肠道菌群及疾病进程中的应用前景。     

Interaction of gut microbiota with dysregulation of bile acids in the pathogenesis of nonalcoholic fatty liver disease and potential therapeutic implications of probiotics

The intestinal microbiota is now recognised to play key roles in health due to its involvement in many aspects of human physiology. Disturbance in gut microbiota (dysbiosis) is thus associated with many diseases including nonalcoholic fatty liver disease (NAFLD) which includes nonalcoholic fatty liver and nonalcoholic steatohepatitis. The mechanisms for the effect of dysbiosis in NAFLD pathogenesis are not completely elucidated. Many explanations have been proposed to trigger dysbiosis, leading to NAFLD including inflammation, ethanol produced by the gut bacteria and lipotoxicity. Recently the roles of bile acids and nuclear receptors are highly regarded. It is well known that gut microbes produce enzymes that convert primary bile acids into secondary bile acids in the intestines. Several studies have demonstrated that disturbance of the intestinal microbiota leads to decreased synthesis of secondary bile acids, which in turn decreases activation of nuclear receptors such as farnesoid X receptor (FXR), pregnane X receptor, Takeda G-protein–coupled bile acid protein 5 and vitamin D receptor. These receptors are important in energy regulation and their dysregulation can cause NAFLD. Therefore, stimulation of nuclear receptors especially FXR has been extensively explored for the amelioration of NAFLD. However, paradoxical effects of nuclear receptor activation are a major problem for the clinical application of nuclear receptor stimuli. We further posit that microbiome restoration could be an alternative approach for the treatment of NAFLD. Several gut bacteria are now known to be involved in bile acid metabolism. It will be necessary to identify which one/ones is/are feasible. Careful selection of commensal bacteria for probiotics may lead to an effective therapy for NAFLD.     

Intestinal Pathology and Gut Microbiota Alterations in a Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Mouse Model of Parkinson’s Disease

Patients with Parkinson’s disease (PD) often have non-motor symptoms related to gastrointestinal (GI) dysfunction, such as constipation and delayed gastric emptying, which manifest prior to the motor symptoms of PD. Increasing evidence indicates that changes in the composition of the gut microbiota may be related to the pathogenesis of PD. However, it is unclear how GI dysfunction occurs and how gut microbial dysbiosis is caused. We investigated whether a neurotoxin model of PD induced by chronic low doses of MPTP is capable of reproducing the clinical intestinal pathology of PD, as well as whether gut microbial dysbiosis accompanies this pathology. C57BL/6 male mice were administered 18 mg/kg MPTP twice per week for 5 weeks via intraperitoneal injection. GI function was assessed by measuring the 1-h stool frequency and fecal water content; motor function was assessed by pole tests; and tyrosine hydroxylase and alpha-synuclein expression were analyzed. Furthermore, the inflammation, intestinal barrier and composition of the gut microbiota were measured. We found that MPTP caused GI dysfunction and intestinal pathology prior to motor dysfunction. The composition of the gut microbiota was changed; in particular, the change in the abundance of Lachnospiraceae, Erysipelotrichaceae, Prevotellaceae, Clostridiales, Erysipelotrichales and Proteobacteria was significant. These results indicate that a chronic low-dose MPTP model can be used to evaluate the progression of intestinal pathology and gut microbiota dysbiosis in the early stage of PD, which may provide new insights into the pathogenesis of PD.     

Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis

Inflammatory bowel disease (IBD) is a multifactorial disease which arises as a result of the interaction of genetic, environmental, barrier and microbial factors leading to chronic inflammation in the intestine. Patients with IBD had a higher risk of developing colorectal carcinoma (CRC), of which the subset was classified as colitis-associated cancers. Genetic polymorphism of innate immune receptors had long been considered a major risk factor for IBD, and the mutations were also recently observed in CRC. Altered microbial composition (termed microbiota dybiosis) and dysfunctional gut barrier manifested by epithelial hyperpermeability and high amount of mucosa-associated bacteria were observed in IBD and CRC patients. The findings suggested that aberrant immune responses to penetrating commensal microbes may play key roles in fueling disease progression. Accumulative evidence demonstrated that mucosa-associated bacteria harbored colitogenic and protumoral properties in experimental models, supporting an active role of bacteria as pathobionts (commensal-derived opportunistic pathogens). Nevertheless, the host factors involved in bacterial dysbiosis and conversion mechanisms from lumen-dwelling commensals to mucosal pathobionts remain unclear. Based on the observation of gut leakiness in patients and the evidence of epithelial hyperpermeability prior to the onset of mucosal histopathology in colitic animals, it was postulated that the epithelial barrier dysfunction associated with mucosal enrichment of specific bacterial strains may predispose the shift to disease-associated microbiota. The speculation of leaky gut as an initiating factor for microbiota dysbiosis that eventually led to pathological consequences was proposed as the “common ground hypothesis”, which will be highlighted in this review. Overall, the understanding of the core interplay between gut microbiota and epithelial barriers at early subclinical phases will shed light to novel therapeutic strategies to manage chronic inflammatory disorders and colitis-associated cancers.     

A role for IL-22 in the relationship between intestinal helminths,gut microbiota and mucosal immunity

The intestinal tract is home to nematodes as well as commensal bacteria (microbiota), which have coevolved with the mammalian host. The mucosal immune system must balance between an appropriate response to dangerous pathogens and an inappropriate response to commensal microbiota that may breach the epithelial barrier, in order to maintain intestinal homeostasis. IL-22 has been shown to play a critical role in maintaining barrier homeostasis against intestinal pathogens and commensal bacteria. Here we review the advances in our understanding of the role of IL-22 in helminth infections, as well as in response to commensal and pathogenic bacteria of the intestinal tract. We then consider the relationship between intestinal helminths and gut microbiota and hypothesize that this relationship may explain how helminths may improve symptoms of inflammatory bowel diseases. We propose that by inducing an immune response that includes IL-22, intestinal helminths may enhance the mucosal barrier function of the intestinal epithelium. This may restore the mucosal microbiota populations from dysbiosis associated with colitis and improve intestinal homeostasis.     

The dynamics of gut‐associated microbial communities during inflammation

Our intestine is host to a large microbial community (microbiota) that educates the immune system and confers niche protection. Profiling of the gut‐associated microbial community reveals a dominance of obligate anaerobic bacteria in healthy individuals. However, intestinal inflammation is associated with a disturbance of the microbiota—known as dysbiosis—that often includes an increased prevalence of facultative anaerobic bacteria. This group contains potentially harmful bacterial species, the bloom of which can further exacerbate inflammation. Here, we review the mechanisms that generate changes in the microbial community structure during inflammation. One emerging concept is that electron acceptors generated as by‐products of the host inflammatory response feed facultative anaerobic bacteria selectively, thereby increasing their prevalence within the community. This new paradigm has broad implications for understanding dysbiosis during gut inflammation and identifies potential targets for intervention strategies.