书讯

<正>人体微生物组化学工业出版社出版[美]D.N.弗雷德里克斯编。本书旨在对人体发现的微生物多样性进行概览,并介绍以往在微生物群落与人体健康关系方面所做的研究工作。全书共十四章,第一章介绍了人体微生物组计划(HMP);第二章和第三章介绍人体微生物组的研究工具;第四章从数学角度解释了微生物群落结构与多     

人体肠道病毒组学研究进展

人体微生物组计划开展近10年来,大量的研究显示人体微生物通过各种方式深刻地影响着人体健康。人体肠道内丰富多样的病毒构成了肠道病毒组,是人体微生物组的重要组成部分,和人体健康密切相关。本文综述了近些年国际上人体肠道病毒组研究的最新进展,分别从人体肠道病毒组的组成特征、肠道病毒组-细菌组-人体间的相互作用及其对人体健康的影响、病毒组研究的技术策略及挑战等方面进行了论述,探讨了肠道病毒组在人体疾病预防和治疗领域应用的可行性。     

人体微生物组

<正>化学工业出版社出版[美]D.N.弗雷德里克斯编。本书旨在对人体发现的微生物多样性进行概览,并介绍以往在微生物群落与人体健康关系方面所做的研究工作。全书共十四章,第一章介绍了人体微生物组计划(HMP);第二章和第三章介绍人体微生物组的研究工具;第四章从数学角度解释了微生物群落结构与多样性;第五至第九章介绍了身体各部位(呼吸道、口腔、生殖     

人体微生物组

<正>化学工业出版社出版[美]D.N.弗雷德里克斯编。本书旨在对人体发现的微生物多样性进行概览,并介绍以往在微生物群落与人体健康关系方面所做的研究工作。全书共十四章,第一章介绍了人体微生物组计划(HMP);第二章和第三章介绍人体微生物组的研究工具;第四章从数学角度解释了微生物群落结构与多样性;第五至第九章介绍了身体各部位(呼吸道、口腔、生殖道和肠道)的微生物群落;第十章和第十一章综述了利用动     

中国科学院微生物组计划启动

正2017年12月20日,中国科学院重点部署项目"人体与环境健康的微生物组共性技术研究"暨"中国科学院微生物组计划"启动会在京举行。这个斥资3 000万元的计划由中科院上海生命科学研究院、生物物理研究所、昆明动物所、生态环境研究中心、青岛生物能源与过程研究所及协和医院等14个单位共同参与。当前,微生物组研究正成为新一轮科技浪潮的前沿阵地。美、加、日、法等国纷纷部署微生物组研究国家计划。我     

人体微生物组研究与人类健康

2016年,医学微生物学与感染病学领域“风声依旧”,继续给世界带来巨大影响。病原微生物与人类之间的关系是一个不断斗争、妥协、共同进化的历史。我们从降临到世界的那一刻,就不再是一个孤独的生命,微生物与我们同行。随着我们不断成长,定居在体内的微生物菌群会发生变化。2016年,以研究人体微生物菌群结构变化与人体健康关系为主要内容的人类微生物组计划(human microbiome)在全球引起了广泛关注......     

口腔微生物与全身健康研究进展

口腔微生物是定植于人体口腔的微生物集合。众多研究证实,口腔微生物与多种口腔感染性疾病及系统性疾病紧密相关。随着“人类微生物组计划”及其他微生物宏基因组学相关项目的开展,人们对口腔微生物群落的认识不断深入。本文基于最新研究进展,就口腔微生物的组成、演替特点、与口腔和全身系统性疾病的关系及与肠道微生物的交互作用进行综述。     

人体微生物群与微生物组

随着微生物群(组)研究的兴起,人体微生物组对机体健康或疾病作用的探索一度呈井喷之势,但研究技术及分析方法仍处于起步阶段,需进一步深入。本文对微生物群和微生物组的概念进行了解释,阐述了人体微生物群与机体的相互作用模式,概括了微生物群与人体有关疾病的关系,提出了人体微生物组研究中的6个关键问题,并对未来的发展方向进行了展望。     

微生物与生命健康专题序言

人体微生物组是指人体内由微生物组成的共生生态群落,其动态平衡与人体健康密切相关。微生物组被公认为可在人体中起调节免疫、代谢、消化吸收作用的重要“器官”,可与包括肺、肠道、阴道、大脑在内的多个器官产生联系,并逐步成为治疗癌症、冠心病、神经系统疾病等疑难杂症的潜在靶点。近年来,随着微生物组测序与分析技术的飞速发展,从微生物组角度发现人体微生物与多种疾病的关系并探索新的治疗方法已成为国际科研的热点与前沿。为了进一步促进人体微生物在生命健康领域的研究,《生物工程学报》特组织出版专题,重点阐述了人体微生物组的研究方法、人体微生物组与疾病以及干预方法等方面的研究进展,为推动微生物组在生命健康领域的快速发展提供理论基础。     

人类口腔微生物组学研究:现状、挑战及机遇

全球超过一半的人口患有口腔疾病,其医护费用与全球十大常见死亡病因的花费相当,而且口腔感染与早产、动脉粥样硬化、肝硬化、糖尿病、阿尔茨海默病等全身性或慢性疾病显著相关,因此,口腔微生物组一直是人类微生物组计划的主要研究对象之一。与人体其他部位比较,口腔微生物组研究具有取样快捷、宿主反应表征方便、干预手段直接有效等特点;同时,超过65%的口腔细菌类群已可培养,诸多代表性菌株的全基因组信息已破译。因此口腔微生物组在菌群内部调控网络及其与宿主互作机制、局部感染对远隔器官的影响机制、以及基于菌群的慢病早期预警等微生物组研究核心科学问题上具备作为模式研究体系与技术示范对象的重要优势。本文在分析口腔微生物组学国际、国内研究现状的基础上,建议尽快启动中国人口腔微生物组计划(China human oral microbiome project,CHOMP),通过产学研协同攻关,开拓基于口腔菌群的口腔及全身系统性疾病的个体化预防、诊断及治疗策略。     

The "most wanted" taxa from the human microbiome for whole genome sequencing

The goal of the Human Microbiome Project (HMP) is to generate a comprehensive catalog of human-associated microorganisms including reference genomes representing the most common species. Toward this goal, the HMP has characterized the microbial communities at 18 body habitats in a cohort of over 200 healthy volunteers using 16S rRNA gene (16S) sequencing and has generated nearly 1,000 reference genomes from human-associated microorganisms. To determine how well current reference genome collections capture the diversity observed among the healthy microbiome and to guide isolation and future sequencing of microbiome members, we compared the HMP's 16S data sets to several reference 16S collections to create a 'most wanted' list of taxa for sequencing. Our analysis revealed that the diversity of commonly occurring taxa within the HMP cohort microbiome is relatively modest, few novel taxa are represented by these OTUs and many common taxa among HMP volunteers recur across different populations of healthy humans. Taken together, these results suggest that it should be possible to perform whole-genome sequencing on a large fraction of the human microbiome, including the 'most wanted', and that these sequences should serve to support microbiome studies across multiple cohorts. Also, in stark contrast to other taxa, the 'most wanted' organisms are poorly represented among culture collections suggesting that novel culture- and single-cell-based methods will be required to isolate these organisms for sequencing.     

Perspectives on human microbiome research ethics

study of ethical, legal, and social implications (ELSI) of human microbiome research has been integral to the Human Microbiome Project (HMP). This study explores core ELSI issues that arose during the first phase of the HMP from the perspective of individuals involved in the research. We conducted semi-structured in-depth interviews with investigators and NIH employees ("investigators") involved in the HMP, and with individuals recruited to participate in the HMP Healthy Cohort Study at Baylor College of Medicine ("recruits"). We report findings related to three major ELSI issues: informed consent, data sharing, and return of results. Our findings demonstrate that investigators and recruits were similarly sensitive to these issues yet generally comfortable with study design in light of current knowledge about the microbiome.     

Focus: Microbiome: The Influence of the Gut Microbiota on Host Physiology: In Pursuit of Mechanisms

The results generated from the NIH funded Human Microbiome Project (HMP) are necessarily tied to the overall mission of the agency, which is to foster scientific discoveries as a basis for protecting and improving health. The investment in the HMP phase 1 accomplished many of its goals including the preliminary characterization of the human microbiome and the identification of links between microbiome diversity and disease states. Going forward, the next step in these studies must involve the identification of the functional molecular elements that mediate the positive influence of a eubiotic microbiome on health and disease. This review will focus on recent advances describing mechanistic events in the intestine elicited by the microbiome. These include symbiotic bacteria-induced activation of redox-dependent cell signaling, the bacterial production of short chain fatty acids and ensuing cellular responses, and the secretion of bacteriocins by bacteria that have anti-microbial activities against potential pathogens.     

Phylotyping and Functional Analysis of Two Ancient Human Microbiomes

Background

The Human Microbiome Project (HMP) is one of the U.S. National Institutes of Health Roadmap for Medical Research. Primary interests of the HMP include the distinctiveness of different gut microbiomes, the factors influencing microbiome diversity, and the functional redundancies of the members of human microbiotas. In this present work, we contribute to these interests by characterizing two extinct human microbiotas.

Methodology/Principal Findings

We examine two paleofecal samples originating from cave deposits in Durango Mexico and dating to approximately 1300 years ago. Contamination control is a serious issue in ancient DNA research; we use a novel approach to control contamination. After we determined that each sample originated from a different human, we generated 45 thousand shotgun DNA sequencing reads. The phylotyping and functional analysis of these reads reveals a signature consistent with the modern gut ecology. Interestingly, inter-individual variability for phenotypes but not functional pathways was observed. The two ancient samples have more similar functional profiles to each other than to a recently published profile for modern humans. This similarity could not be explained by a chance sampling of the databases.

Conclusions/Significance

We conduct a phylotyping and functional analysis of ancient human microbiomes, while providing novel methods to control for DNA contamination and novel hypotheses about past microbiome biogeography. We postulate that natural selection has more of an influence on microbiome functional profiles than it does on the species represented in the microbial ecology. We propose that human microbiomes were more geographically structured during pre-Columbian times than today.     

The Human Microbiome Project in 2011 and beyond

The human microbiome comprises the genes and genomes of the microbiota that inhabit the body. We highlight Human Microbiome Project (HMP) resources, including 600 microbial reference genomes, 70 million 16S sequences, 700 metagenomes, and 60 million predicted genes from healthy adult microbiomes. Microbiome studies of specific diseases and future research directions are also discussed.     

Metabolic reconstruction for metagenomic data and its application to the human microbiome

Microbial communities carry out the majority of the biochemical activity on the planet, and they play integral roles in processes including metabolism and immune homeostasis in the human microbiome. Shotgun sequencing of such communities' metagenomes provides information complementary to organismal abundances from taxonomic markers, but the resulting data typically comprise short reads from hundreds of different organisms and are at best challenging to assemble comparably to single-organism genomes. Here, we describe an alternative approach to infer the functional and metabolic potential of a microbial community metagenome. We determined the gene families and pathways present or absent within a community, as well as their relative abundances, directly from short sequence reads. We validated this methodology using a collection of synthetic metagenomes, recovering the presence and abundance both of large pathways and of small functional modules with high accuracy. We subsequently applied this method, HUMAnN, to the microbial communities of 649 metagenomes drawn from seven primary body sites on 102 individuals as part of the Human Microbiome Project (HMP). This provided a means to compare functional diversity and organismal ecology in the human microbiome, and we determined a core of 24 ubiquitously present modules. Core pathways were often implemented by different enzyme families within different body sites, and 168 functional modules and 196 metabolic pathways varied in metagenomic abundance specifically to one or more niches within the microbiome. These included glycosaminoglycan degradation in the gut, as well as phosphate and amino acid transport linked to host phenotype (vaginal pH) in the posterior fornix. An implementation of our methodology is available at http://huttenhower.sph.harvard.edu/humann. This provides a means to accurately and efficiently characterize microbial metabolic pathways and functional modules directly from high-throughput sequencing reads, enabling the determination of community roles in the HMP cohort and in future metagenomic studies.     

A Taxonomic Signature of Obesity in the Microbiome? Getting to the Guts of the Matter

Obesity is an important and intractable public health problem. In addition to the well-known risk factors of behavior, diet, and genetics, gut microbial communities were recently identified as another possible source of risk and a potential therapeutic target. However, human and animal-model studies have yielded conflicting results about the precise nature of associations between microbiome composition and obesity. In this paper, we use publicly available data from the Human Microbiome Project (HMP) and MetaHIT, both surveys of healthy adults that include obese individuals, plus two smaller studies that specifically examined lean versus obese adults. We find that inter-study variability in the taxonomic composition of stool microbiomes far exceeds differences between lean and obese individuals within studies. Our analyses further reveal a high degree of variability in stool microbiome composition and diversity across individuals. While we confirm the previously published small, but statistically significant, differences in phylum-level taxonomic composition between lean and obese individuals in several cohorts, we find no association between BMI and taxonomic composition of stool microbiomes in the larger HMP and MetaHIT datasets. We explore a range of different statistical techniques and show that this result is robust to the choice of methodology. Differences between studies are likely due to a combination of technical and clinical factors. We conclude that there is no simple taxonomic signature of obesity in the microbiota of the human gut.     

Statistical Object Data Analysis of Taxonomic Trees from Human Microbiome Data

Human microbiome research characterizes the microbial content of samples from human habitats to learn how interactions between bacteria and their host might impact human health. In this work a novel parametric statistical inference method based on object-oriented data analysis (OODA) for analyzing HMP data is proposed. OODA is an emerging area of statistical inference where the goal is to apply statistical methods to objects such as functions, images, and graphs or trees. The data objects that pertain to this work are taxonomic trees of bacteria built from analysis of 16S rRNA gene sequences (e.g. using RDP); there is one such object for each biological sample analyzed. Our goal is to model and formally compare a set of trees. The contribution of our work is threefold: first, a weighted tree structure to analyze RDP data is introduced; second, using a probability measure to model a set of taxonomic trees, we introduce an approximate MLE procedure for estimating model parameters and we derive LRT statistics for comparing the distributions of two metagenomic populations; and third the Jumpstart HMP data is analyzed using the proposed model providing novel insights and future directions of analysis.     

Oral spirochetes implicated in dental diseases are widespread in normal human subjects and carry extremely diverse integron gene cassettes

The NIH Human Microbiome Project (HMP) has produced several hundred metagenomic data sets, allowing studies of the many functional elements in human-associated microbial communities. Here, we survey the distribution of oral spirochetes implicated in dental diseases in normal human individuals, using recombination sites associated with the chromosomal integron in Treponema genomes, taking advantage of the multiple copies of the integron recombination sites (repeats) in the genomes, and using a targeted assembly approach that we have developed. We find that integron-containing Treponema species are present in ～80% of the normal human subjects included in the HMP. Further, we are able to de novo assemble the integron gene cassettes using our constrained assembly approach, which employs a unique application of the de Bruijn graph assembly information; most of these cassette genes were not assembled in whole-metagenome assemblies and could not be identified by mapping sequencing reads onto the known reference Treponema genomes due to the dynamic nature of integron gene cassettes. Our study significantly enriches the gene pool known to be carried by Treponema chromosomal integrons, totaling 826 (598 97% nonredundant) genes. We characterize the functions of these gene cassettes: many of these genes have unknown functions. The integron gene cassette arrays found in the human microbiome are extraordinarily dynamic, with different microbial communities sharing only a small number of common genes.