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.     

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.     

肠道微生物样本库:伦理考量和管理规范

 人体微生物组与健康和疾病的关系是重要的科学问题。而人体微生物样本库的建立是人体微生物组研究的重要基础,这个新兴领域迫切要求对已建立的价值体系和伦理规范进行调整和变革。本文讨论人体微生物样本库建设中的知情同意、样本和数据的所有权、隐私和风险等;并以粪菌库和粪菌移植为典型案例,分析选择"最佳"、"健康"供体所面临的医学和伦理困难;提出了人体微生物样本库监管的政策建议。     

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.     

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.     

营养与免疫关系及其研究进展

蛋白质、氨基酸和脂肪是构成机体免疫系统的基本物质,维生素和微量元素是参与机体免疫系统功能的重要组成成分.本文从营养与免疫的关系出发,分别综述了蛋白质、脂肪、氨基酸、维生素微量元素等营养成分对机体免疫功能的影响.     

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.     

Adhesion receptors of the immune system

The adhesive interactions of cells with other cells and with the extracellular matrix are crucial to all developmental processes, but have a central role in the functions of the immune system throughout life. Three families of cell-surface molecules regulate the migration of lymphocytes and the interactions of activated cells during immune responses.     

The plant immune system

Many plant-associated microbes are pathogens that impair plant growth and reproduction. Plants respond to infection using a two-branched innate immune system. The first branch recognizes and responds to molecules common to many classes of microbes, including non-pathogens. The second responds to pathogen virulence factors, either directly or through their effects on host targets. These plant immune systems, and the pathogen molecules to which they respond, provide extraordinary insights into molecular recognition, cell biology and evolution across biological kingdoms. A detailed understanding of plant immune function will underpin crop improvement for food, fibre and biofuels production.     

Reciprocal interactions of the intestinal microbiota and immune system

The emergence of the adaptive immune system in vertebrates set the stage for evolution of an advanced symbiotic relationship with the intestinal microbiota. The defining features of specificity and memory that characterize adaptive immunity have afforded vertebrates the mechanisms for efficiently tailoring immune responses to diverse types of microbes, whether to promote mutualism or host defence. These same attributes can put the host at risk of immune-mediated diseases that are increasingly linked to the intestinal microbiota. Understanding how the adaptive immune system copes with the remarkable number and diversity of microbes that colonize the digestive tract, and how the system integrates with more primitive innate immune mechanisms to maintain immune homeostasis, holds considerable promise for new approaches to modulate immune networks to treat and prevent disease.     

Diversity, stability and resilience of the human gut microbiota

Trillions of microbes inhabit the human intestine, forming a complex ecological community that influences normal physiology and susceptibility to disease through its collective metabolic activities and host interactions. Understanding the factors that underlie changes in the composition and function of the gut microbiota will aid in the design of therapies that target it. This goal is formidable. The gut microbiota is immensely diverse, varies between individuals and can fluctuate over time - especially during disease and early development. Viewing the microbiota from an ecological perspective could provide insight into how to promote health by targeting this microbial community in clinical treatments.     

肠内免疫营养剂用于结直肠癌手术前的准备

目的:探讨肠内免疫营养剂用于结直肠癌手术前准备的疗效,并与传统方法对比。方法:按入组条件将40例结直肠癌病人随机分为肠内免疫营养组(EN组)20例,传统方法组(对照组)20例。EN组用免疫营养剂作术前肠道准备,不用禁食、灌肠及服用抗生素;传统方法组采用禁食、机械灌肠和口服抗生素。比较两组免疫、营养指标(血清IgG、IgM、IgA和血清白蛋白、前白蛋白、转铁蛋白),肠道清洁度,肠功能恢复时间和手术后并发症(吻合口漏、切口感染和腹腔内感染)。结果:肠道清洁度比较无统计学意义(P>0 05);术后肠功能恢复时间比较,EN组为(28 4±5 8)h,对照组为(59 3±7 5)h,两组相比有统计学意义(P<0 0001);EN组肠道准备前与术后各免疫、营养指标比较无统计学意义(P>0 05),对照组术后各免疫、营养指标较肠道准备前有显著下降(P<0 01),两组免疫、营养指标肠道准备前与术后差异相比较有统计学意义(P<0 05);两组病人术后并发症发生率的比较无统计学意义(P>0 05)。结论:采用肠内免疫营养剂作结直肠癌手术前准备可改善病人免疫功能和营养状态,保证肠道良好的清洁度,并能加快术后肠功能恢复时间,手术后并发症少。     

Asynchronous replication and allelic exclusion in the immune system.

The development of mature B cells involves a series of molecular decisions which culminate in the expression of a single light-chain and heavy-chain antigen receptor on the cell surface. There are two alleles for each receptor locus, so the ultimate choice of one receptor type must involve a process of allelic exclusion. One way to do this is with a feedback mechanism that downregulates rearrangement after the generation of a productive receptor molecule, but recent work suggests that monoallelic epigenetic changes may also take place even before rearrangement. To better understand the basis for distinguishing between alleles, we have analysed DNA replication timing. Here we show that all of the B-cell-receptor loci (mu, kappa and lambda) and the TCRbeta locus replicate asynchronously. This pattern, which is established randomly in each cell early in development and maintained by cloning, represents an epigenetic mark for allelic exclusion, because it is almost always the early-replicating allele which is initially selected to undergo rearrangement in B cells. These results indicate that allelic exclusion in the immune system may be very similar to the process of X chromosome inactivation.     

Defining the core Arabidopsis thaliana root microbiome

Land plants associate with a root microbiota distinct from the complex microbial community present in surrounding soil. The microbiota colonizing the rhizosphere (immediately surrounding the root) and the endophytic compartment (within the root) contribute to plant growth, productivity, carbon sequestration and phytoremediation. Colonization of the root occurs despite a sophisticated plant immune system, suggesting finely tuned discrimination of mutualists and commensals from pathogens. Genetic principles governing the derivation of host-specific endophyte communities from soil communities are poorly understood. Here we report the pyrosequencing of the bacterial 16S ribosomal RNA gene of more than 600 Arabidopsis thaliana plants to test the hypotheses that the root rhizosphere and endophytic compartment microbiota of plants grown under controlled conditions in natural soils are sufficiently dependent on the host to remain consistent across different soil types and developmental stages, and sufficiently dependent on host genotype to vary between inbred Arabidopsis accessions. We describe different bacterial communities in two geochemically distinct bulk soils and in rhizosphere and endophytic compartments prepared from roots grown in these soils. The communities in each compartment are strongly influenced by soil type. Endophytic compartments from both soils feature overlapping, low-complexity communities that are markedly enriched in Actinobacteria and specific families from other phyla, notably Proteobacteria. Some bacteria vary quantitatively between plants of different developmental stage and genotype. Our rigorous definition of an endophytic compartment microbiome should facilitate controlled dissection of plant-microbe interactions derived from complex soil communities.