肠道菌群稳态与结直肠癌研究进展

结直肠癌是一种涉及遗传、环境和生活方式等多风险因素的疾病。越来越多的研究表明肠道菌群在结直肠癌的发生发展中起重要作用,菌群与消化道之间的共生作用对维持肠道内环境的稳定也十分重要。菌群在炎症、药物代谢,甚至癌症的发展中扮演着许多角色,然而由感染、饮食或生活方式等变化引起的菌群组成的改变却可影响这种共生关系。同样,菌群组成的变化使部分菌种在肠内引发炎症反应甚至致癌,从而对结肠直肠癌的发生发展产生实质性的影响,综述将总结目前肠道菌群与结直肠癌之间潜在的联系,重点关注细菌在肠道中所参与的各种反应,从而为治疗结直肠癌提供更多的研究思路。     

饮食调节与肠道菌群研究的进展及展望

随着人体肠道菌群研究的不断深入,菌群的结构、功能被发现与人类的多种疾病之间存在显著的关联。除遗传因素外,生活方式及饮食习惯可以在很大程度上改变人体肠道菌群的稳态平衡,因此通过饮食干预调节肠道菌群,从而改善人体健康状况将是未来的研究热点之一。该文对疾病状态下肠道菌群种类和丰度的变化进行了总结,综述了饮食调节对肠道菌群的影响及反馈作用的研究进展,以期为今后通过饮食干预的方式改善人类健康状况的个性化精准医疗提供参考。     

肠道菌群功能与影响因素研究进展

人体肠道作为一种营养丰富的天然环境有多达100兆个微生物,其中绝大多数存于结肠内,密度接近1011~1012/m L。人类肠道内的微生物多样性是微生物菌落和宿主共同进化的结果,自然选择和进化使肠道菌群与宿主处于一种动态平衡且稳定的关系。文章综述了肠道菌群对宿主可能产生的影响以及引起肠道菌群发生改变的某些因素,肠道微生物影响宿主的代谢、营养吸收、免疫功能以及神经功能调节,而饮食及其他条件又能引起肠道菌群的改变。深入分析肠道菌群的具体结构、探索不同微生物在宿主体内究竟发挥着怎样的作用以及如何充分利用微生物的不同特性改善人类健康应成为今后研究的重点方向。     

多糖与肠道菌群相互作用及其构效关系研究进展

肠道菌群是一个复杂的生态系统,影响宿主的饮食、疾病发展、药物代谢和免疫系统调节等诸多生理方面。多糖广泛存在于动物、植物及微生物中,具有多种生理活性。肠道菌群与多糖相互作用,消化难以消化的多糖,多糖作为肠道菌群的重要能量来源,促进益生菌增殖。肠道菌群紊乱导致疾病的发生,多糖通过调节肠道菌群改善疾病。随着“人类微生物组计划”的启动和国内外学者对肠道菌群的深入研究,多糖与肠道菌群的关系逐渐清晰,但多糖的结构与肠道菌群之间的关系还有待进一步探究。因此,本文综述了多糖与肠道菌群的相互作用,并通过调节肠道菌群的组成来改善疾病,以及从多糖的分子量、糖苷键、单糖组成三方面探讨多糖与肠道菌群的构效关系,同时对未来研究的方向进行展望,以期为治疗疾病的深入研究提供重要参照和建议。     

肠道菌群与肥胖关系的研究进展

西方化的高脂饮食方式造成了越来越多的肥胖人群。高脂饮食在一定程度上可以改变肠道菌群的结构组成和功能,促进宿主对食物营养的吸收,从而增加体重形成肥胖。高脂饮食诱导的肥胖者肠道菌群的改变会导致宿主能量吸收增加,肠道通透性和炎症增加,而有减肥功能的短链脂肪酸合成能力下降。最近研究发现肠道菌群也可以通过影响中枢神经系统,尤其是下丘脑相关基因的表达来控制食欲,从而调控肥胖的形成。本文系统介绍了最近几年高脂饮食诱导肥胖的研究,总结了一些与肥胖形成有密切关系的肠道菌群以及其在肥胖形成中的作用机制,为进一步研究肠道菌群与肥胖之间的调控作用奠定了基础。最后总结了肠道菌群可以作为一个预防和治疗肥胖的有效靶点,可以通过在食物中添加有益菌或者通过菌群移植来治疗肥胖。     

饮食与肠道菌群关系的研究进展

人体肠道内含有大量的微生物,直接参与了机体的各种代谢活动,与人体健康密切相关。研究显示肠道菌群的构成和稳定受到诸多宿主和环境因素的影响,其中饮食因素起着至关重要的作用。特别是西方高脂饮食方式造成肠道菌群结构改变,从而导致一些慢性、非传染性和免疫相关性疾病的发生。在过去的几十年中,肠道菌群在人体健康中的作用越来越受到关注。不同饮食结构可以对肠道菌群的组成和多样性产生重要的影响。在这篇综述中,我们总结了肠道微生物与人体健康之间的关系以及益生菌在饮食中的作用,为指导和建立健康饮食结构提供理论指导,为相应疾病的防治提供参考。     

肠道菌群影响因素的研究进展

肠道菌群是动物体内最复杂、最庞大的微生态系统,其多样性和组成在调节宿主的健康、生理、发育和环境适应等方面具有不可替代的作用.肠道菌群受多种因素的综合影响.综述宿主遗传因素、食物和高海拔环境对肠道菌群的影响.     

微生态制剂在老年人肠道菌群失衡中的应用

人类从青年到老年这个过程,随着年龄的增长,退行性和感染性疾病的易感性也增加,其可能与人体肠道菌群失衡有着密切的关系。人体肠道内生理菌群对机体健康具有重要的作用,其变化与宿主的免疫功能、食物、疾病和年龄等有关。了解老年人肠道菌群特点,且在老年人肠道菌群失调相关疾病中合理介入微生态制剂,将大大有利于老年人身体健康。本文就老年人肠道菌群失衡相关疾病以及微生态制剂在这些疾病中的应用进行综述。     

肠道真菌研究进展

真菌菌群是肠道菌群的重要组成部分,在肠道微生态稳态的维持和宿主的免疫调节中发挥重要作用。肠道真菌失调通常和肠道疾病甚至肠道外疾病有关。本文就肠道真菌的定殖与组成、真菌菌群对肠道微生态的调控、菌群失调促进疾病的发展机制、基于肠道真菌的治疗策略和肠道真菌的鉴定分析方法等方面的进展进行了综述和展望,旨在系统认识肠道真菌调节宿主健康和促进疾病发生的机制,为相关疾病的诊断和治疗提供重要参考。     

肠道菌群对代谢相关性脂肪肝的影响及运动干预研究进展

大量研究表明,肠道菌群与神经退行性疾病和代谢性疾病等多种疾病的发生和发展息息相关,菌群的种类和数量会受到遗传、饮食习惯、运动等因素的影响。在代谢相关脂肪性肝病中,肠道菌群的部分代谢物通过增加肝脏脂肪变性、改变肠道黏膜通透性等方式对疾病的发展起到促进作用,菌群的种类和数量变化与病情进展的关系也被广泛研究,但是两者发生的先后顺序仍不十分明确。运动可以增加肠道有益菌群的种类和数量,同时改善高脂饮食导致的肠道菌群紊乱,并有效缓解代谢相关脂肪性肝病的病情,肠道菌群也能对机体的运动能力产生影响,但运动是如何通过肠道菌群来改善代谢相关脂肪性肝病的机制尚不十分明确。本文通过综述三者的相互关系来阐述肠道菌群和运动在代谢相关脂肪性肝病中发挥的重要作用。     

Arthritis susceptibility and the gut microbiome

Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology though both genetic and environmental factors have been suggested to be involved in its pathogenesis. While infections and other environmental factors (e.g. smoking) have been studied extensively and show some association, a direct link between all the factors has been difficult to prove. With the recent advances in technology, it has become possible to sequence the commensals that are residing in our gut. The gut microbiome may provide the missing link to this puzzle and help solve the mystery of many leaky gut syndromes. The gut commensals are involved in maintaining host immune homeostasis and function suggesting that they might be critical in altering the immune system, which leads to autoimmune diseases like RA. Mouse models support the role of the gut microbiota in predisposition to RA. If that is true, the power of gut-derived commensal can be harnessed to our benefit by generating a biomarker profile along with genetic factors to define individuals at risk and by altering the gut microbial composition using various means.     

Gut microbiome and the risk factors in central nervous system autoimmunity

Humans are colonized after birth by microbial organisms that form a heterogeneous community, collectively termed microbiota. The genomic pool of this macro-community is named microbiome. The gut microbiota is essential for the complete development of the immune system, representing a binary network in which the microbiota interact with the host providing important immune and physiologic function and conversely the bacteria protect themselves from host immune defense. Alterations in the balance of the gut microbiome due to a combination of environmental and genetic factors can now be associated with detrimental or protective effects in experimental autoimmune diseases. These gut microbiome alterations can unbalance the gastrointestinal immune responses and influence distal effector sites leading to CNS disease including both demyelination and affective disorders. The current range of risk factors for MS includes genetic makeup and environmental elements. Of interest to this review is the consistency between this range of MS risk factors and the gut microbiome. We postulate that the gut microbiome serves as the niche where different MS risk factors merge, thereby influencing the disease process.     

Unravelling the effects of the environment and host genotype on the gut microbiome

To what extent do host genetics control the composition of the gut microbiome? Studies comparing the gut microbiota in human twins and across inbred mouse lines have yielded inconsistent answers to this question. However, candidate gene approaches, in which one gene is deleted or added to a model host organism, show that a single host gene can have a tremendous effect on the diversity and population structure of the gut microbiota. Now, quantitative genetics is emerging as a highly promising approach that can be used to better understand the overall architecture of host genetic influence on the microbiota, and to discover additional host genes controlling microbial diversity in the gut. In this Review, we describe how host genetics and the environment shape the microbiota, and how these three factors may interact in the context of chronic disease.     

从肠道菌群角度认识阿尔茨海默病的潜在发病机制

过去10年中,人们逐渐认识到肠道微生物群的多样性及菌群平衡在维护宿主健康中发挥的作用。肠道微生物及其代谢产物通过一系列的生化、免疫和生理功能环节与宿主进行交流,从而影响宿主的稳态和健康。阿尔茨海默病(Alzheimer’s disease,AD)是一种复杂的神经退行性疾病,其易感性和发展过程受年龄、遗传和表观遗传等因素的影响。研究发现,肠道微生物群的紊乱(组成改变和易位)与神经系统疾病(AD)有关,胃肠道通过肠脑轴与中枢神经系统进行沟通,包括对神经的直接作用、内分泌途径和免疫调控方式。动物模型、粪便菌群移植及益生菌干预为肠道菌群与AD的相关性提供了证据。外漏的细菌代谢产物可能直接损害神经元功能,也可能诱发神经炎症,促进AD的发病。本文主要综述了肠道微生物群与AD的关联和作用机制,以期为通过改善肠道菌群结构预防AD的可能干预措施提供依据。     

Host genetic and environmental effects on mouse intestinal microbiota

The mammalian gut harbors complex and variable microbial communities, across both host phylogenetic space and conspecific individuals. A synergy of host genetic and environmental factors shape these communities and account for their variability, but their individual contributions and the selective pressures involved are still not well understood. We employed barcoded pyrosequencing of V1-2 and V4 regions of bacterial small subunit ribosomal RNA genes to characterize the effects of host genetics and environment on cecum assemblages in 10 genetically distinct, inbred mouse strains. Eight of these strains are the foundation of the Collaborative Cross (CC), a panel of mice derived from a genetically diverse set of inbred founder strains, designed specifically for complex trait analysis. Diversity of gut microbiota was characterized by complementing phylogenetic and distance-based, sequence-clustering approaches. Significant correlations were found between the mouse strains and their gut microbiota, reflected by distinct bacterial communities. Cohabitation and litter had a reduced, although detectable effect, and the microbiota response to these factors varied by strain. We identified bacterial phylotypes that appear to be discriminative and strain-specific to each mouse line used. Cohabitation of different strains of mice revealed an interaction of host genetic and environmental factors in shaping gut bacterial consortia, in which bacterial communities became more similar but retained strain specificity. This study provides a baseline analysis of intestinal bacterial communities in the eight CC progenitor strains and will be linked to integrated host genotype, phenotype and microbiota research on the resulting CC panel.     

肠道菌群与相关疾病

近年来肠道菌群的研究发展迅速,肠道菌群对宿主消化、代谢和免疫功能的影响逐渐被人们所熟知并重视。大量研究提示,肠道菌群的改变可能引发代谢、肝脏和肠道等方面的多种相关疾病。因此,研究肠道菌群对宿主健康及疾病的影响尤为重要,也能为预防和治疗肠道菌群相关疾病提供建议。     

蜜蜂肠道菌群定殖研究进展

肠道菌群在其宿主健康中发挥着各种各样的重要功能。蜜蜂是高度社会化的昆虫,其肠道菌群与大多数昆虫明显不同,由兼性厌氧和微好氧的细菌组成,具有高度保守性和专门的核心肠道微生物群。近年来的研究表明,蜜蜂肠道微生物群在代谢、免疫功能、生长发育以及保护机体免受病原体侵袭等方面起着重要作用,并已证实肠道微生物在蜜蜂健康和疾病中起着重要作用,肠道微生物群的破坏对蜜蜂健康会产生不利影响。本文综述了蜜蜂肠道菌群的特征及菌群定殖研究进展,介绍了蜜蜂的日龄、群体、季节等对蜜蜂肠道菌群定殖的影响,探讨了宿主的功能和新陈代谢对肠道菌群的影响。     

肠道微生物多样性与能量代谢调控及肥胖关系的研究进展

肠道微生物与宿主之间相互选择,构成了一个相对稳定的超有机体。宿主基因型和遗传关系影响肠道微生物的生态学特征,而肠道微生物发酵肠道内多糖,为宿主提供可吸收利用的养分,增强肠道对养分吸收的能力。同时,肠道微生物还影响一些转录因子的活性,调控宿主基因的表达,增强宿主甘油三酯的合成和脂肪沉积,减少脂肪酸氧化分解,调控宿主能量代谢。     

结直肠癌与肠道微生物群研究进展

肠道微生物群是人体内环境的重要组成部分,与宿主共进化、共代谢、共发育,并与宿主之间相互调控,影响宿主健康。近年研究显示,肠道微生物群参与了结直肠癌的发生和发展。了解肠道微生物群的特征性变化及其诱发结直肠癌的机制对于结直肠癌的防治有着重要意义。目前以肠道微生物群为靶点的干预性基础研究也取得了一些突破性的研究进展。本文主要对结直肠癌患者肠道微生物群的变化、其可能的致病机制及临床相关研究进展等进行综述。     

Gut microbiota,inflammation, and molecular signatures of host response to infection

Gut microbial dysbiosis has been linked to many noncommunicable diseases. However, little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying host response to infection. Here, we describe the construction of a proteomic risk score based on 20 blood proteomic biomarkers, which have recently been identified as molecular signatures predicting the progression of the COVID-19. We demonstrate that in our cohort of 990 healthy individuals without infection, this proteomic risk score is positively associated with proinflammatory cytokines mainly among older, but not younger, individuals. We further discover that a core set of gut microbiota can accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model and that these gut microbiota features are highly correlated with proinflammatory cytokines in another independent set of 366 individuals. Fecal metabolomics analysis suggests potential amino acid-related pathways linking gut microbiota to host metabolism and inflammation. Overall, our multi-omics analyses suggest that gut microbiota composition and function are closely related to inflammation and molecular signatures of host response to infection among healthy individuals. These results may provide novel insights into the cross-talk between gut microbiota and host immune system.