Proteomics at the interface of psychology, gut physiology and dysfunction: an underexploited approach that deserves expansion

Gut functions such as digestion and absorption are essential to life and the emerging insights into the gut-brain axis - that is, the cross talk between the enteric and CNS - point towards critical links between (eating) behavior, psychology, whole body and gut physiology, and digestive and overall health. While proteomics is ideally positioned to shed more light on these interactions, be it applied to the periphery (e.g., blood) or the locus of action (i.e., the gut), it is to date largely underexploited, mainly because of challenging sampling and tissue complexity. In view of the contrast between potential and current delivery of proteomics in the context of intestinal health, this article briefs the reader on the state-of-the-art of molecular intestinal research, reviews current proteomic studies (explicitly focusing on the most recent ones that target inflammatory bowel disease patient samples) and argues for an expansion of this research field.     

中国人群肠道微生物鸟枪法宏基因组测序研究进展

肠道微生物与人类健康的相关性研究仍然是当前生命科学研究领域的前沿热点之一。不依赖培养的16Sr RNA基因高通量测序是当前的主要研究手段。但随着测序成本的降低和数据分析方法的日渐成熟,宏基因组鸟枪法测序因具有信息量更大、更全等优势,将逐渐成为今后一段时间内研究肠道微生物组的重要手段。美国在人类微生物组计划的资助下,对30 805份样品进行了肠道微生物宏基因测序分析。通过NCBI Pub Med和SRA数据库检索,共发现72项研究收集了约10000份中国人的肠道样品用于宏基因组测序。但到目前为止,仅56项研究进行了公开发表,其中与代谢性疾病相关的文献16篇,与感染和免疫性疾病相关的文献16篇,与心脑血管疾病相关的文献12篇。由于采样地点以北京、广州、上海等大城市为主,测序平台和测序分析方法均存在较大差异,且大部分研究仍以相关性分析为主,相关研究成果在临床疾病诊疗中所发挥的作用仍非常有限。规范采样方法、标准化测序平台和数据分析流程,开展多中心平行研究将有助于数据整合和比较分析。同时,结合使用转录组、蛋白质组和培养组学等多组学方法开展功能验证和分子作用机制研究,将有利于更好地将肠道微生物研究...     

动物及其肠道菌群的协同进化研究

动物自身合成一些关键营养物质的能力缺失,转而依赖体内的共生物来完成相应功能,如动物体内共生细菌能帮助宿主从食物中提取营养物质,并能合成一些关键代谢反应的化合物。结合国内外在动物及其肠道菌群的协同进化的研究进展,从三个方面进行了归纳:(1)动物及其肠道微生物组成与功能的协同进化研究;(2)动物行为与肠道微生物的关系;(3)共生肠道微生物在人类或动物自身消化食物、营养获取、健康和疾病方面发挥的重要作用。     

人体肠道噬菌体的研究与应用

肠道是人体内微生物定殖最丰富的部位。近年来,随着肠道菌群与人体健康疾病关联研究的蓬勃发展,肠道噬菌体也逐渐引起关注。然而,相关信息技术和实验技术发展的滞后在一定程度上限制了肠道噬菌体的科学研究进程。因此,本文首先回顾了近几年来肠道噬菌体研究领域所开发或采用的计算和实验方法,包括噬菌体的测序数据分析和噬菌体的分离纯化等。随后,本文就肠道噬菌体的分类、肠道内噬菌体与细菌的互作及肠道噬菌体在人体疾病干预中的应用展开了讨论。最后,本文展望了肠道噬菌体研究在数据和实体资源、信息和实验技术、与肠道菌群的互作、干预和治疗人体疾病各方面的一系列挑战和机遇。     

Gut microbes in cardiovascular diseases and their potential therapeutic applications

Microbial ecosystem comprises a complex community in which bacteria interact with each other.The potential roles of the intestinal microbiome play in human health have gained considerable attention.The imbalance of gut microbial community has been looked to multiple chronic diseases.Cardiovascular diseases(CVDs)are leading causes of morbidity worldwide and are influ-enced by genetic and environmental factors.Recent advances have provided scientific evidence that CVD may also be attributed to gut microbiome.in this review,we highlight the complex interplay between microbes,their metabolites,and the potential influence on the generation and development of CVDs.The therapeutic potentiai of using intestinal microbiomes to treat CVD is also discussed.it is quite possible that gut microbes may be used for clinical treatments of CVD in the near future.     

Gut microbiome dysbiosis and honeybee health

Since a few decades, apiculture is facing important economic losses worldwide with general major consequences in many areas of agriculture. A strong attention has been paid towards the phenomenon named Colony Collapse Disorder in which colonies suddenly disappear with no clear explanations. Honeybee colonies can be affected by abiotic factors, such as environmental pollution or insecticide applications for agricultural purposes. Also biotic stresses cause colony losses, including bacterial (e.g. Paenibacillus larvae) and fungal (e.g. Ascosphaera apis) pathogens, microsporidia (e.g. Nosema apis), parasites (i.e. Varroa destructor) and several viruses. In the light of recent research, intestinal dysbiosis, considered as the relative disproportion of the species within the native microbiota, has shown to affect human and animal health. In arthropods, alteration of the gut microbial climax community has been shown to be linked to health and fitness disequilibrium, like in the medfly Ceratitis capitata for which low mate competitiveness is determined by a gut microbial community imbalance. According to these observations, it is possible to hypothesize that dysbiosis may have a role in disease occurrence also in honeybees. Here we aim to discuss the current knowledge on dysbiosis in the honeybee and its relation with honeybee health by reviewing the investigations of the microbial diversity associated to honeybees and the recent experiments performed to control bee diseases by microbial symbionts. We conclude that, despite the importance of a good functionality of the associated microbiota in preserving insect health has been proved, the mechanisms involved in honeybee gut dysbiosis are still unknown. Accurate in vitro, in vivo and in field investigations are required under healthy, diseased and stressed conditions for the host.     

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。     

Proteomics,human gut microbiota and probiotics

The various bacterial communities associated with humans have many functions and the gut microbiota has a major role in the host. Bacterial imbalance in the gut, known as dysbiosis, has therefore been linked to several diseases. Probiotics, that is, microbial strains that have beneficial effects on the host, are thought to benefit this intestinal ecosystem. Hence, knowledge of the gut microbiota composition and an understanding of its functionalities are of interest. Recently, efforts have focused on developing new high-throughput techniques for studying microbial cells and complex communities. Among them, proteomics is increasingly being used. The purpose of this article is to focus on the recent development of this technology and its usefulness in analyzing the human gut ecosystem and probiotic strains.     

The Gut Microbiota–Brain Axis Expands Neurologic Function: A Nervous Rapport

Does exploration of the gut microbiota–brain axis expand our understanding of what it means to be human? Recognition and conceptualization of a gut microbiota–brain axis challenges our study of the nervous system. Here, integrating gut microbiota–brain research into the metaorganism model is proposed. The metaorganism—an expanded, dynamic unit comprising the host and commensal organisms—asserts a radical blurring between man and microbe. The metaorganism nervous system interacts with the exterior world through microbial‐colored lenses. Ongoing studies have reported that gut microbes contribute to brain function and pathologies, even shaping higher neurological functions. How will continued collaborative efforts (e.g., between neurobiology and microbiology), including partnerships with the arts (e.g., philosophy), contribute to the knowledge of microbe‐to‐mind interactions? While this is not a systemic review, this nascent field is briefly described, highlighting ongoing challenges and recommendations for emerging gut microbiota–brain research. Also see the video abstract here https://youtu.be/lP9gOW8StXg .     

肠道菌群：肠道干细胞增殖分化的调节者

肠道干细胞(intestinal stem cells, ISCs)是肠道各类上皮细胞的来源,通过平衡增殖与分化维持肠道稳态。同时,肠道菌群及其代谢物在维持宿主肠道稳态中也发挥着重要作用。随着技术的发展,研究者认识到ISCs与肠道菌群之间存在相互作用。研究表明,ISCs对上皮细胞亚型的调控影响肠道菌群的组成,并且肠道菌群及其代谢物也影响ISCs介导的上皮发育。本文阐述了ISCs分化对肠道菌群的影响,重点总结了肠道菌群及其代谢物调控ISCs增殖分化的研究进展,从菌群调控ISCs的角度探讨肠道损伤的治疗思路,并对未来可能的研究方向进行讨论。     

人类肠道微生物组与相关疾病研究进展

人体肠道共生着数以万亿计的微生物,肠道微生物在维持宿主正常生理功能中发挥重要作用,其成分和功能变化可导致严重的肠道和全身性疾病。以新一代测序技术和生物信息学分析为基础的元基因组学研究不仅极大地推动了对人类肠道微生物的整体认识,还加深了对肠道微生物代谢产物促进人类健康机理的理解,为肠道炎症、代谢性疾病和癌症等人类疾病的诊断与治疗提供了新思路。就肠道微生物元基因组学与肠道相关疾病的研究进展作一综述。     

肠道微生物功能宏基因组学与代谢组学关联分析方法研究进展

近年来基于高通量基因测序的微生物组学研究极大加深了人们对微生物与健康和疾病关系的认识。然而基因测序方法不能直接测定微生物的功能活性,难以鉴定微生物中的关键功能分子,单独使用无法回答肠道微生物何种成员通过何种方式影响宿主等关键科学问题。单一组学研究弊端尽显,多组学联用势在必行。肠道微生物代谢组学以微生物群落所有小分子代谢物为研究对象,可发现肠道微生物随宿主病理生理变化的关键代谢物,为微生物组-宿主互作机制研究提供线索,成为微生物组学研究的重要补充。肠道微生物功能基因组学与代谢组学关联分析在宿主生理、疾病病理、药物药理等方面取得众多进展,展现良好应用前景。然而目前肠道微生物功能基因组学与代谢组学关联分析存在方法滥用、相关性结论与生物学知识相悖等突出问题。为帮助正确应用肠道微生物功能宏基因组学与代谢组学关联分析,本文综述了各种多组学数据整合分析方法的原理、优缺点与适用范围,并给出了应用建议。     

肠道微生物与血清素互作研究进展

肠道微生物在肠道稳态和大脑健康中发挥着举足轻重的作用.血清素是大脑的一种重要的单胺类神经递质,90％以上在结肠肠嗜铬细胞中由色氨酸代谢转化而来,在机体发挥广泛作用.近年来的研究表明,血清素对机体发挥的作用可能受到肠道微生物影响.肠道中某些微生物具有产生血清素的能力,同时,微生物群及其代谢产物(如丁酸)能通过影响色氨酸羟...     

Gut microbial diversity across a contact zone for California voles: Implications for lineage divergence of hosts and mitonuclear mismatch in the assembly of the mammalian gut microbiome

Gut microbial diversity is thought to reflect the co‐evolution of microbes and their hosts as well as current host‐specific attributes such as genetic background and environmental setting. To explore interactions among these parameters, we characterized variation in gut microbiome composition of California voles (Microtus californicus) across a contact zone between two recently diverged lineages of this species. Because this contact zone contains individuals with mismatched mitochondrial‐nuclear genomes (cybrids), it provides an important opportunity to explore how different components of the genotype contribute to gut microbial diversity. Analyses of bacterial 16S rRNA sequences and joint species distribution modelling revealed that host genotypes and genetic differentiation among host populations together explained more than 50% of microbial community variation across our sampling transect. The ranked importance (most to least) of factors contributing to gut microbial diversity in our study populations were: genome‐wide population differentiation, local environmental conditions, and host genotypes. However, differences in microbial communities among vole populations (β‐diversity) did not follow patterns of lineage divergence (i.e., phylosymbiosis). Instead, among‐population variation was best explained by the spatial distribution of hosts, as expected if the environment is a primary source of gut microbial diversity (i.e., dispersal limitation hypothesis). Across the contact zone, several bacterial taxa differed in relative abundance between the two parental lineages as well as among individuals with mismatched mitochondrial and nuclear genomes. Thus, genetic divergence among host lineages and mitonuclear genomic mismatches may also contribute to microbial diversity by altering interactions between host genomes and gut microbiota (i.e., hologenome speciation hypothesis).     

Living the high life: Could gut microbiota matter for adaptation to high altitude?

At high altitude, the reduced availability of thermal energy and oxygen poses major challenges to organisms. Different species or populations have evolved similar solutions to these challenges, such as blood flow regulation in animals (Bouverot, 1985). Previous studies investigating such convergent adaptations have primarily looked at changes in host genomes (e.g., see Scheinfeldt & Tishkoff, 2010), but have rarely considered the potential role of the gut microbiome in mediating host adaptation. As gut microbes can indirectly regulate host blood pressure (Pluznick, 2014) and energy intake efficiency, it has been hypothesized that they could help maintain normal energy production and/or optimize nutritional assimilation in high‐altitude hypoxic environments (e.g., Li & Zhao, 2015). However, it has been hard to (a) show that there is a direct effect of altitude on the gut microbiota, because of the many potential confounding effects of altitude (e.g., diet is correlated to altitude, as well as to the microbiome) and to (b) understand the mechanisms by which the microbiota could mediate host hypoxic and thermoregulatory stresses. In this issue of Molecular Ecology, Suzuki, Martins, and Nachman (2018) show that, independently of diet, taxonomic composition and functions of mouse gut microbiota converge in independent high‐altitude environments and propose the intriguing hypothesis that some of these functional convergences might be beneficial to their host.     

Gut microbiota,host health,and polysaccharides

The intestinal microbiota is a complicated ecosystem that influences many aspects of host physiology (i.e. diet, disease development, drug metabolism, and regulation of the immune system). It also exhibits spatial patterning and temporal dynamics. In this review, the effects of internal and external (environmental) factors on intestinal microbiota are discussed. We describe the roles of the gut microbiota in maintaining intestinal and immune system homeostasis and the relationship between gut microbiota and diseases. In particular, the contributions of polysaccharides, as the most abundant diet components in intestinal microbiota and host health are presented. Finally, perspectives for research avenues relating to gut microbiota are also discussed.     

肠道微生物群与脱发的相关性研究进展

随着年轻人群脱发比例的逐年增加,头发健康问题日益受到关注。脱发会影响人们的生活质量,并对心理和社交生活产生巨大影响。近年来,对肠道微生物群的生理功能性研究已不再仅仅局限于胃肠道。研究表明肠道和肠道微生物群与皮肤有密切关系,提示“肠-皮肤轴”的存在。本文在已有的“肠-皮肤轴”研究现状基础上,总结近年来文献资料,探讨肠道微生物群与脱发之间可能的联系和潜在机制,为脱发的发病机制和治疗靶点提供新的认识和观点。     

Integrated gut/liver microphysiological systems elucidates inflammatory inter‐tissue crosstalk

A capability for analyzing complex cellular communication among tissues is important in drug discovery and development, and in vitro technologies for doing so are required for human applications. A prominent instance is communication between the gut and the liver, whereby perturbations of one tissue can influence behavior of the other. Here, we present a study on human gut‐liver tissue interactions under normal and inflammatory contexts, via an integrative multi‐organ platform comprising human liver (hepatocytes and Kupffer cells), and intestinal (enterocytes, goblet cells, and dendritic cells) models. Our results demonstrated long‐term (>2 weeks) maintenance of intestinal (e.g., barrier integrity) and hepatic (e.g., albumin) functions in baseline interaction. Gene expression data comparing liver in interaction with gut, versus isolation, revealed modulation of bile acid metabolism. Intestinal FGF19 secretion and associated inhibition of hepatic CYP7A1 expression provided evidence of physiologically relevant gut‐liver crosstalk. Moreover, significant non‐linear modulation of cytokine responses was observed under inflammatory gut‐liver interaction; for example, production of CXCR3 ligands (CXCL9,10,11) was synergistically enhanced. RNA‐seq analysis revealed significant upregulation of IFNα/β/γ signaling during inflammatory gut‐liver crosstalk, with these pathways implicated in the synergistic CXCR3 chemokine production. Exacerbated inflammatory response in gut‐liver interaction also negatively affected tissue‐specific functions (e.g., liver metabolism). These findings illustrate how an integrated multi‐tissue platform can generate insights useful for understanding complex pathophysiological processes such as inflammatory organ crosstalk. Biotechnol. Bioeng. 2017;114: 2648–2659. © 2017 Wiley Periodicals, Inc.     

基于代谢组学的植物多酚及其肠道健康效应研究进展

综述了植物多酚的分类和来源、在代谢组学技术的驱动下,新型多酚物质的鉴定、控制植物多酚合成途径的关键因子以及多酚的功能特性的研究进展,阐述了植物多酚在肠道中的代谢以及其作为“益生元”调节肠道微生态并影响机体健康的重要功能。目前的研究表明不同植物多酚在调节肠道微生态方面存在差异,多数有促进肠道有益菌作用,并通过与肠道微生物“互作”发挥促进健康效应。总之,植物多酚作为“益生元”影响人体健康可能离不开肠道微生物的介导。各个植物多酚的益生功能也需要进一步阐析,在此过程中需要考虑宿主,膳食等混杂因素的综合影响,且需要拓展临床应用方面的研究。     

果蝇肠道共生菌对宿主作用的研究进展

肠道共生菌是动物体内的重要组成部分,在宿主的生长发育和健康等方面发挥着重要作用,近年来已成为国内外的研究热点.果蝇作为研究肠道微生物菌群功能的优秀模型,在肠道共生菌与宿主关系研究方面已取得许多重要进展.在本文中,我们首先对果蝇肠道微生物的组成和特征作了总结,然后对果蝇肠道共生菌在其生长发育、营养与代谢、行为反应、寿命以...