Enterotypes of the human gut microbiome

Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.     

Structure, function and diversity of the healthy human microbiome

Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat's signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81-99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.     

An obesity-associated gut microbiome with increased capacity for energy harvest

The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.     

Ecology drives a global network of gene exchange connecting the human microbiome

Horizontal gene transfer (HGT), the acquisition of genetic material from non-parental lineages, is known to be important in bacterial evolution. In particular, HGT provides rapid access to genetic innovations, allowing traits such as virulence, antibiotic resistance and xenobiotic metabolism to spread through the human microbiome. Recent anecdotal studies providing snapshots of active gene flow on the human body have highlighted the need to determine the frequency of such recent transfers and the forces that govern these events. Here we report the discovery and characterization of a vast, human-associated network of gene exchange, large enough to directly compare the principal forces shaping HGT. We show that this network of 10,770 unique, recently transferred (more than 99% nucleotide identity) genes found in 2,235 full bacterial genomes, is shaped principally by ecology rather than geography or phylogeny, with most gene exchange occurring between isolates from ecologically similar, but geographically separated, environments. For example, we observe 25-fold more HGT between human-associated bacteria than among ecologically diverse non-human isolates (P = 3.0 × 10(-270)). We show that within the human microbiome this ecological architecture continues across multiple spatial scales, functional classes and ecological niches with transfer further enriched among bacteria that inhabit the same body site, have the same oxygen tolerance or have the same ability to cause disease. This structure offers a window into the molecular traits that define ecological niches, insight that we use to uncover sources of antibiotic resistance and identify genes associated with the pathology of meningitis and other diseases.     

2021年人类微生物组研究热点回眸

人类微生物组(human microbiome)指生活在人体上的互生、共生和致病的所有微生物及其遗传物质的总和.近年来,人类微生物组研究加速推进,研究内容愈加广泛和深入,其科学意义愈加凸显,被视作"人体的另一个器官".从人类微生物组的组成和分布特征、在全生命周期中的作用、与疾病发生发展的关系、对营养代谢和药物功能的影响...     

Human gut microbiome viewed across age and geography

Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization.     

Metagenomic analysis of a permafrost microbial community reveals a rapid response to thaw

Permafrost contains an estimated 1672?Pg carbon (C), an amount roughly equivalent to the total currently contained within land plants and the atmosphere. This reservoir of C is vulnerable to decomposition as rising global temperatures cause the permafrost to thaw. During thaw, trapped organic matter may become more accessible for microbial degradation and result in greenhouse gas emissions. Despite recent advances in the use of molecular tools to study permafrost microbial communities, their response to thaw remains unclear. Here we use deep metagenomic sequencing to determine the impact of thaw on microbial phylogenetic and functional genes, and relate these data to measurements of methane emissions. Metagenomics, the direct sequencing of DNA from the environment, allows the examination of whole biochemical pathways and associated processes, as opposed to individual pieces of the metabolic puzzle. Our metagenome analyses reveal that during transition from a frozen to a thawed state there are rapid shifts in many microbial, phylogenetic and functional gene abundances and pathways. After one week of incubation at 5?°C, permafrost metagenomes converge to be more similar to each other than while they are frozen. We find that multiple genes involved in cycling of C and nitrogen shift rapidly during thaw. We also construct the first draft genome from a complex soil metagenome, which corresponds to a novel methanogen. Methane previously accumulated in permafrost is released during thaw and subsequently consumed by methanotrophic bacteria. Together these data point towards the importance of rapid cycling of methane and nitrogen in thawing permafrost.     

基于宏基因组数据的微生物群落比较方法

宏基因组学是一门研究直接来自环境的基因材料的新兴学科。传统的微生物学研究,依赖于实验室培养,而宏基因组学,使得对这些未被培养或不可培养的微生物的研究成为可能,也为同一环境中微生物之间相互作用的研究,以及微生物群落的整体研究,指明了新的方向。随着测序技术的迅速发展,大量宏基因组测序数据不断产生,对新的统计分析方法提出了更高的要求。简要介绍了宏基因组学以及其中的几个重要问题,主要针对其中基于测序数据的群落比较问题进行论述,介绍了多种现今常用的统计计算方法,并分析了它们的适用情况。     

口腔益生菌的研究现状

口腔是一个复杂而完整的微生态系统。生活方式、外源性致病菌等外源因子可扰乱口腔微生物组与其宿主之间的共生关系引发龋齿、牙周炎、牙龈炎、口臭等口腔疾病。益生菌是一类活的并对人类机体局部或全身性健康都具有有益作用的微生物。传统上,益生菌被广泛用于功能性食品、医药保健、饲料等各个领域,最常见的用途是治疗或预防胃肠道感染和疾病,改善肠道健康。近十年,各种研究表明益生菌可通过抑制致病菌生长,改善口腔微生物菌群,调节口腔免疫力等方式对各种口腔疾病产生积极的防治效果。作为一种新兴的机体健康维护概念,维护口腔健康的益生菌及其作用机制日益受到国内外学者的密切关注,综述了口腔益生菌在常见口腔疾病中的潜在作用机制,阐述了利用口腔益生菌在防治口腔疾病时所面临的重要问题,同时在口腔益生菌未来的发展趋势和开发方向等方面剖析如何更好地利用口腔益生菌驱动健康食品产业发展,以期为口腔益生菌的深入研究及其在食品工业中的开发应用提供相应参考。     

垃圾渗滤液处理厂活性污泥微生物种群结构和功能分析

对垃圾渗滤液处理厂活性污泥的16S rRNA基因和宏基因组进行高通量测序并分析, 探究垃圾渗滤液处理厂活性污泥微生物的种群结构、氮循环和有机污染物降解相关功能微生物和功能基因。结果表明, Calditrichaeota门微生物丰度最高(58.77%), 其次是 Proteobacteria (16.80%)和Bacteroides (6.19%); Calorithrix属是活性污泥的优势菌属(58.77%); 活性污泥中存在硝化、反硝化、同化硝酸盐还原、异化硝酸盐还原和氮固定 5 条氮循环途径, 反硝化相关基因丰度最高(78.84%), 主要分布于Calditrichaeota, Proteobacteria和Choroflexi中; 硝化作用由氨氧化菌Nitrosomonas完成。活性污泥中含有丰富的难降解有机污染物降解基因, Proteobacteria, Bacteroides, Planctomycetes, Calditrichaeota和Choroflexi是典型的有机污染物降解功能微生物。     

Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice

The composite human microbiome of Western populations has probably changed over the past century, brought on by new environmental triggers that often have a negative impact on human health. Here we show that consumption of a diet high in saturated (milk-derived) fat, but not polyunsaturated (safflower oil) fat, changes the conditions for microbial assemblage and promotes the expansion of a low-abundance, sulphite-reducing pathobiont, Bilophila wadsworthia. This was associated with a pro-inflammatory T helper type 1 (T(H)1) immune response and increased incidence of colitis in genetically susceptible Il10(?/?), but not wild-type mice. These effects are mediated by milk-derived-fat-promoted taurine conjugation of hepatic bile acids, which increases the availability of organic sulphur used by sulphite-reducing microorganisms like B. wadsworthia. When mice were fed a low-fat diet supplemented with taurocholic acid, but not with glycocholic acid, for example, a bloom of B. wadsworthia and development of colitis were observed in Il10(?/?) mice. Together these data show that dietary fats, by promoting changes in host bile acid composition, can markedly alter conditions for gut microbial assemblage, resulting in dysbiosis that can perturb immune homeostasis. The data provide a plausible mechanistic basis by which Western-type diets high in certain saturated fats might increase the prevalence of complex immune-mediated diseases like inflammatory bowel disease in genetically susceptible hosts.     

宏基因组技术及其在厌氧消化研究中的应用

在介绍基因（组）富集、基因（组）DNA提取、文库构建及筛选等宏基因组技术的基础上,论述了宏基因组技术在厌氧消化研究中应用的重要性,认为该技术可成为研究微生物群落多样性的首选技术之一,有助于了解厌氧消化微生物的多样性、生态功能和动态变化,揭示厌氧消化微生物学机理,提高厌氧消化效能等.同时宏基因组技术为微生物资源的深层次开发利用提供了技术平台,并在工业、农业、海洋等领域具有广泛的应用前景.     

Metagenomic and functional analysis of hindgut microbiota of a wood-feeding higher termite

From the standpoints of both basic research and biotechnology, there is considerable interest in reaching a clearer understanding of the diversity of biological mechanisms employed during lignocellulose degradation. Globally, termites are an extremely successful group of wood-degrading organisms and are therefore important both for their roles in carbon turnover in the environment and as potential sources of biochemical catalysts for efforts aimed at converting wood into biofuels. Only recently have data supported any direct role for the symbiotic bacteria in the gut of the termite in cellulose and xylan hydrolysis. Here we use a metagenomic analysis of the bacterial community resident in the hindgut paunch of a wood-feeding 'higher' Nasutitermes species (which do not contain cellulose-fermenting protozoa) to show the presence of a large, diverse set of bacterial genes for cellulose and xylan hydrolysis. Many of these genes were expressed in vivo or had cellulase activity in vitro, and further analyses implicate spirochete and fibrobacter species in gut lignocellulose degradation. New insights into other important symbiotic functions including H2 metabolism, CO2-reductive acetogenesis and N2 fixation are also provided by this first system-wide gene analysis of a microbial community specialized towards plant lignocellulose degradation. Our results underscore how complex even a 1-microl environment can be.     

人类微生物组发展态势及建议

 近年来，基因组测序与分析技术的进步推动了人类微生物组研究的发展，进一步解析人体微生物组与全生命周期健康、疾病的发生发展、营养/药物功效发挥的关系，并由此带来健康与医疗理念的变革。通过全面分析全球人类微生物组发展趋势，发现当前人类微生物组参考序列解析仍处于起步阶段，由“普查”人类微生物组的构成与分布逐步扩展到解析特定人群的微生物组。随着研究的深入，人类微生物组功能的因果机制解析逐渐成为研究重点，基于人类微生物组重构进行健康干预受到更多关注。中国已经开展了大量人类微生物组基础研究，在粪菌移植等特定应用方向取得了一定的进展，但仍面临缺少对大规模人群样本的长期跟踪分析、研究系统性需进一步加强、高价值微生物组重构产品自主创新能力不足、产品开发存在监管漏洞等问题。提出了推动中国人类微生物组发展的政策建议。     

Functional metagenomic profiling of nine biomes

Microbial activities shape the biogeochemistry of the planet and macroorganism health. Determining the metabolic processes performed by microbes is important both for understanding and for manipulating ecosystems (for example, disruption of key processes that lead to disease, conservation of environmental services, and so on). Describing microbial function is hampered by the inability to culture most microbes and by high levels of genomic plasticity. Metagenomic approaches analyse microbial communities to determine the metabolic processes that are important for growth and survival in any given environment. Here we conduct a metagenomic comparison of almost 15 million sequences from 45 distinct microbiomes and, for the first time, 42 distinct viromes and show that there are strongly discriminatory metabolic profiles across environments. Most of the functional diversity was maintained in all of the communities, but the relative occurrence of metabolisms varied, and the differences between metagenomes predicted the biogeochemical conditions of each environment. The magnitude of the microbial metabolic capabilities encoded by the viromes was extensive, suggesting that they serve as a repository for storing and sharing genes among their microbial hosts and influence global evolutionary and metabolic processes.     

北部湾海洋微生物物种多样性与化学多样性研究进展

北部湾海域是我国生物多样性最丰富的海域之一,为人类发展提供了大量的生物资源。北部湾还蕴含着极丰富的微生物资源,是新物种、新基因、新药物、新生物材料的潜在来源。为更全面地了解北部湾海洋微生物的研究现状,促进北部湾海洋微生物资源的研究和开发利用,本文综述了北部湾海洋微生物的物种多样性和代谢产物活性成分多样性,为深入研究北部湾海洋微生物,开发和利用北部湾海洋微生物资源提供参考。     

双歧杆菌对慢性腹泻猕猴肠道微生物组的影响

本研究旨在结合高通量测序和平板计数实验探索含活性双歧杆菌(Bifidobacterium spp)的饲料对慢性腹泻猕猴(Macaca mulatta)肠道微生物多样性及其腹泻症状的影响.通过16S rRNA高通量测序对比分析添加双歧杆菌前后饲料的菌群组成，发现添加组双歧杆菌的相对丰度显著高于未添加组(P<0.05).向慢性腹泻猕猴投喂该饲料，一个月后收集粪便进行宏基因组测序，并与前期研究获得的未添加组慢性腹泻猕猴和健康猕猴的肠道宏基因组数据对比分析，发现添加组的肠道菌群中乳杆菌(Lactobacillus spp)相对丰度较未添加组显著上调(P<0.05)，与健康组无显著差异(P>0.05).最后对饲喂双歧杆菌后好转及持续腹泻猕猴的粪便进行乳杆菌平板计数实验.发现经饲喂，猕猴肠道中乳杆菌数量增加，验证了宏基因组测序分析的结果.     

活性污泥宏基因组Fosmid文库的构建

大插入片段宏基因组文库的构建是开发大片段目的基因及分析其结构与功能的基础.文中分别采用十六烷基三甲基溴化铵(CTAB)法、试剂盒及琼脂糖包埋法提取活性污泥宏基因组DNA,其中琼脂糖包埋法获得的DNA片段大于23kbp,利用此DNA成功构建了以pCC1FOS为载体的Fosmid文库,该文库含有5280个克隆,平均插入片段长度为35～40 kbp,共包含约200 Mbp的宏基因组DNA.从此文库中随机挑选200个克隆,利用活性筛选方法快速筛选到了1个含有淀粉酶的阳性克隆,表明活性污泥Fosmid文库可用于功能基因的活性筛选,具有开发新基因的潜力.     

宏基因组学技术与微生物群落多样性分析方法

从宏基因组学的2个主要技术——扩增子测序与宏基因组测序出发,对其在微生物群落检测中的基本分析流程进行了介绍.概述了微生物群落多样性的概念、相关的统计分析原理以及相关分析结果的解析方法等.提出利用正处于蓬勃发展时期的大数据分析技术与手段来克服宏基因组学数据解析,并将分析结果用更易理解的形式展现出来是未来研究的重点和难点,...