Shuttling of information between the mucosal and luminal environment drives intestinal homeostasis

The gastrointestinal tract is a passageway for dietary nutrients, microorganisms and xenobiotics. The gut is home to diverse bacterial communities forming the microbiota. While bacteria and their metabolites maintain gut homeostasis, the host uses innate and adaptive immune mechanisms to cope with the microbiota and luminal environment. In recent years, multiple bi-directional instructive mechanisms between microbiota, luminal content and mucosal immune systems have been uncovered. Indeed, epithelial and immune cell-derived mucosal signals shape microbiota composition, while microbiota and their by-products shape the mucosal immune system. Genetic and environmental perturbations alter gut mucosal responses which impact on microbial ecology structures. On the other hand, changes in microbiota alter intestinal mucosal responses. In this review, we discuss how intestinal epithelial Paneth and goblet cells interact with the microbiota, how environmental and genetic disorders are sensed by endoplasmic reticulum stress and autophagy responses, how specific bacteria, bacterial- and diet-derived products determine the function and activation of the mucosal immune system. We will also discuss the critical role of HDAC activity as a regulator of immune and epithelial cell homeostatic responses.     

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。     

肠道微生物培养的研究进展及应用

肠道中栖居着组成复杂、功能多样的微生物群,这些微生物群在宿主免疫、营养吸收、代谢调节等方面发挥着重要作用。随着测序技术的快速发展,肠道微生物研究通过16S rRNA基因测序和宏基因组测序产生了大量的数据,其中许多未组装的序列成为微生物“暗物质”。近年来,不少研究利用多种不同微生物分离培养方法,结合高通量鉴定技术,从人、小鼠、猪肠道中分离了大量的微生物,丰富了菌株资源,为解析微生物“暗物质”以及后续肠道微生物功能和应用研究提供了基础和保障。尽管微生物的可培养性受到多种因素的影响,大部分微生物尚处于“未培养”的状态,但无论是病因研究还是生理和遗传特征的解析都离不开微生物实体资源的获取。肠道微生物的分离培养对微生物研究从关联分析向菌群功能验证、因果机制解析和功能菌株开发的深入研究具有重要意义。本文旨在探讨和综述影响微生物可培养性的因素,总结回顾肠道微生物的培养方法并阐述肠道微生物培养研究的进展,以期为肠道微生物培养研究提供新的视角。     

The human microbiota associated with overall health

Human body harbors diverse microbes, the main components include bacteria, eukaryotes and viruses. Emerging evidences show that the human microbiota is intrinsically linked with overall health. The development of next-generation sequencing provides an unprecedented opportunity to investigate the complex microbial communities that are associated with the human body. Many factors like host genetics and environmental factors have a major impact on the composition and dynamic changes of human microbiota. The purpose of this paper is to present an overview of the relationship between human health and human microbiota (skin, nasal, throat, oral, vaginal and gut microbiota), then to focus on the factors modulating the composition of the microbiota and the future challenges to manipulate the microbiota for personalized health.     

Intestinal microbiota and the immune system in metabolic diseases

The intestinal microbiota is comprised of millions of microorganisms that reside in the gastrointestinal tract and consistently interact with the host. Host factors such as diet and disease status affect the composition of the microbiota, while the microbiota itself produces metabolites that can further manipulate host physiology. Dysbiosis of the intestinal microbiota has been characterized in patients with certain metabolic diseases, some of which involve damage to the host intestinal epithelial barrier and alterations in the immune system. In this review, we will discuss the consequences of dietdependent bacterial dysbiosis in the gastrointestinal tract, and how the associated interaction with epithelial and immune cells impacts metabolic diseases.     

Microbial (co)infections: Powerful immune influencers

It is well established that by modulating various immune functions, host infection may alter the course of concomitant inflammatory diseases, of both infectious and autoimmune etiologies. Beyond the major impact of commensal microbiota on the immune status, host exposure to viral, bacterial, and/or parasitic microorganisms also dramatically influences inflammatory diseases in the host, in a beneficial or harmful manner. Moreover, by modifying pathogen control and host tolerance to tissue damage, a coinfection can profoundly affect the development of a concomitant infectious disease. Here, we review the diverse mechanisms that underlie the impact of (co)infections on inflammatory disorders. We discuss epidemiological studies in the context of the hygiene hypothesis and shed light on the sometimes dual impact of germ exposure on human susceptibility to inflammatory disease. We then summarize the immunomodulatory mechanisms at play, which can involve pleiotropic effects of immune players and discuss the possibility to harness pathogen-derived compounds to the host benefit.     

Gut microbiota and immunity relevance in eubiosis and dysbiosis

Human gut is colonized by numerous microorganisms, in which bacteria present the highest proportion of this colonization that live in a symbiotic relationship with the host. This microbial collection is commonly known as the microbiota. The gut microbiota can mediate gut epithelial and immune cells interaction through vitamins synthesis or metabolic products. The microbiota plays a vital role in growth and development of the main components of human’s adaptive and innate immune system, while the immune system regulates host-microbe symbiosis. On the other hand, negative alteration in gut microbiota composition or gut dysbiosis, can disturb immune responses. This review highlights the gut microbiota-immune system cross-talk in both eubiosis and dysbiosis.     

皮肤共生菌在皮肤健康和疾病中的作用研究进展

人体皮肤上有多种微生物定居,这些微生物群落的组成、分布和动态变化对皮肤的健康状况和疾病有着重要的调节作用.然而,人们一直不清楚皮肤微生物群落如何影响人类健康.对皮肤共生菌进行深入研究,不仅有助于发现有益皮肤共生菌菌株,也有助于筛选相应皮肤疾病新的药物靶标.近年来,对皮肤共生菌与宿主之间相互影响和作用机制的研究逐渐深入,...     

肠道微生物与人体健康研究进展

人类肠道中定居着许多对宿主有益的微生物,包括细菌、病毒、真核生物等,它们在肠道内能与其他微生物及免疫系统相互作用,对人体健康具有重要影响,被称为"被遗忘的器官",它们的基因组也被誉为人类的"第二基因组",与人体的能量代谢及物质代谢有关。本文总结了人体肠道中病毒、真核生物、细菌和宿主免疫系统的相互作用,微生物群的失衡可能导致的疾病如肥胖和克罗恩病等,以及微生物环境在人体内的成熟过程,期望有助于诊断和治疗与肠道微生物失衡相关的疾病。     

Role of the enteric microbiota in intestinal homeostasis and inflammation

The mammalian intestine encounters many more microorganisms than any other tissue in the body thus making it the largest and most complex component of the immune system. Indeed, there are greater than 100 trillion (10¹⁴) microbes within the healthy human intestine, and the total number of genes derived from this diverse microbiome exceeds that of the entire human genome by at least 100-fold. Our coexistence with the gut microbiota represents a dynamic and mutually beneficial relationship that is thought to be a major determinant of health and disease. Because of the potential for intestinal microorganisms to induce local and/or systemic inflammation, the intestinal immune system has developed a number of immune mechanisms to protect the host from pathogenic infections while limiting the inflammatory tissue injury that accompanies these immune responses. Failure to properly regulate intestinal mucosal immunity is thought to be responsible for the inflammatory tissue injury observed in the inflammatory bowel diseases (IBD; Crohn disease, ulcerative colitis). An accumulating body of experimental and clinical evidence strongly suggests that IBD results from a dysregulated immune response to components of the normal gut flora in genetically susceptible individuals. The objective of this review is to present our current understanding of the role that enteric microbiota play in intestinal homeostasis and pathogenesis of chronic intestinal inflammation.     

鱼类肠道微生物与宿主免疫系统相互作用研究进展

鱼类肠道中存在大量微生物,对于维持宿主健康具有重要作用。鱼类免疫系统能够监视并调控肠道微生物组成,维持肠道菌群稳态。同时,鱼类肠道共生微生物调节鱼类免疫系统,抑制病原微生物的过度增殖,保证宿主的健康。本文回顾了鱼类肠道微生物与宿主免疫系统相互作用的研究进展,重点介绍了宿主免疫系统识别肠道微生物、塑造肠道菌群以及益生菌对宿主免疫和肠道菌群的调控等,提出了理想的益生菌应该来自动物自身胃肠道,生产中应谨慎选用非宿主来源的益生菌,以期为推动鱼类肠道功能微生物开发和应用提供理论支撑。     

Symbiosis and development: the hologenome concept

All animals and plants establish symbiotic relationships with microorganisms; often the combined genetic information of the diverse microbiota exceeds that of the host. How the genetic wealth of the microbiota affects all aspects of the holobiont's (host plus all of its associated microorganisms) fitness (adaptation, survival, development, growth and reproduction) and evolution is reviewed, using selected coral, insect, squid, plant, and human/mouse published experimental results. The data are discussed within the framework of the hologenome theory of evolution, which demonstrates that changes in environmental parameters, for example, diet, can cause rapid changes in the diverse microbiota, which not only can benefit the holobiont in the short term but also can be transmitted to offspring and lead to long lasting cooperations. As acquired characteristics (microbes) are heritable, consideration of the holobiont as a unit of selection in evolution leads to neo-Lamarckian principles within a Darwinian framework. The potential application of these principles can be seen in the growing fields of prebiotics and probiotics.     

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.     

The impact of the gut microbiota on human health: an integrative view

The human gut harbors diverse microbes that play a fundamental role in the well-being of their host. The constituents of the microbiota--bacteria, viruses, and eukaryotes--have been shown to interact with one another and with the host immune system in ways that influence the development of disease. We review these interactions and suggest that a holistic approach to studying the microbiota that goes beyond characterization of community composition and encompasses dynamic interactions between all components of the microbiota and host tissue over time will be crucial for building predictive models for diagnosis and treatment of diseases linked to imbalances in our microbiota.     

Role of microorganisms in the evolution of animals and plants: the hologenome theory of evolution

We present here the hologenome theory of evolution, which considers the holobiont (the animal or plant with all of its associated microorganisms) as a unit of selection in evolution. The hologenome is defined as the sum of the genetic information of the host and its microbiota. The theory is based on four generalizations: (1) All animals and plants establish symbiotic relationships with microorganisms. (2) Symbiotic microorganisms are transmitted between generations. (3) The association between host and symbionts affects the fitness of the holobiont within its environment. (4) Variation in the hologenome can be brought about by changes in either the host or the microbiota genomes; under environmental stress, the symbiotic microbial community can change rapidly. These points taken together suggest that the genetic wealth of diverse microbial symbionts can play an important role both in adaptation and in evolution of higher organisms. During periods of rapid changes in the environment, the diverse microbial symbiont community can aid the holobiont in surviving, multiplying and buying the time necessary for the host genome to evolve. The distinguishing feature of the hologenome theory is that it considers all of the diverse microbiota associated with the animal or the plant as part of the evolving holobiont. Thus, the hologenome theory fits within the framework of the 'superorganism' proposed by Wilson and Sober.     

口腔未培养微生物分离培养策略的研究进展

口腔微生物是人体微生物组的重要组成部分,其群落组成丰富且独特。现有研究显示,口腔微生物与龋病、牙周炎等口腔健康问题有直接的联系,因而具有重要的研究价值。随着高通量测序技术的发展,人们对口腔中未培养微生物多样性的认识不断加深,这进一步催生对微生物分离培养技术需求的增加。为此,本文将围绕口腔未培养微生物及其分离培养策略的研究进展,首先介绍口腔中未培养微生物的研究现状;其次分析口腔微生物分离培养中可能的限制因素;最后综述微生物分离培养技术发展及其在口腔未培养微生物研究中的应用。全文旨在为口腔未培养微生物的分离培养提供思路和技术参考。     

The gut microbiota in the metagenomics era: sometimes a friend, sometimes a foe

The normal intestinal microflora (microbiota) represents a complex, dynamic, and diverse collection of microorganisms, which usually inhabit the gastrointestinal tract. Normally, between this flora and the human host a mutually beneficial long-term symbiotic relationship is established, where the host contributes essential nutrients necessary for the survival of the microbiota and the latter fulfils multiple roles in host nutrition and development. Several achievements have recently converged to renew interest in studying the normal gut microbiota: the development of molecular methods of studying the microbial communities, the improved understanding of host-microbe interactions in health and disease, and the potential for therapeutic manipulation of the microbiota. We present recent data concerning the molecular technologies of studying the microbiota and new findings regarding the composition of the normal flora. We underline the beneficial activities of the gut flora on the human host. We emphasize the recent findings in the alterations of the microbiota in various medical conditions (celiac disease, irritable bowel syndrome, obesity, colorectal cancer, allergic disorders, and especially inflammatory bowel diseases). The results of these new studies suggest that changes of the microbiota could be linked to the etiopathogenesis of these diseases. These outstanding findings could be used for further diagnostic tools and/or therapy.     

动物宿主——肠道微生物代谢轴研究进展

肠道中栖息着数量庞大且复杂多样的微生物菌群,在维持宿主肠道微环境稳态中发挥重要作用。微生物菌群可以利用宿主肠道的营养素,发酵产生代谢产物,与宿主机体形成宿主—微生物代谢轴(host-microbe metabolic axis)。该代谢轴既能影响营养素吸收和能量代谢,又可调控宿主各项生理过程。本文主要阐述宿主-肠道微生物代谢轴的概念、肠-肝轴、肠-脑轴、肠道微生物与宿主肠道代谢轴的互作以及对机体健康的影响。     

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.     

模式动物在共生微生物研究中的作用

共生微生物是一类定殖于宿主体表或体内, 可执行宿主本身无法完成的功能, 并依赖于宿主所提供的生长环境的微生物。众多研究表明, 人体肠道共生微生物与免疫、营养、代谢, 甚至精神健康等生理功能密切相关, 是重要的“微生物器官”。在早期的肠道微生物研究中, 模式动物就已经作为研究工具被使用。随着肠道微生物研究的不断深入, 模式动物作为不可替代的研究对象发挥了越来越重要的作用。本综述主要对几种重要的模式动物如斑马鱼(Danio rerio)、小鼠(Mus musculus)、猪(Sus scrofa domesticus)和猕猴(Macaca mulatta)在肠道微生物研究中的应用进行了总结, 介绍了各种模式动物的发展过程及特点, 各自在应用于研究时的优缺点, 以及利用这些动物模型在共生微生物领域所取得的一些标志性的科研成果。同时, 也就近年来在共生微生物领域新兴的一些模式生物如蜜蜂(Apis)、果蝇(Drosophila)、秀丽隐杆线虫(Caenorhabditis elegans)等进行了一些探讨。旨在让该领域的研究者们了解模式动物与人体在共生微生物方面的异同, 为更好地利用这一研究工具提供参考。