Metaproteomic and Metabolomic Approaches for Characterizing the Gut Microbiome

The gut microbiome has been shown to play a significant role in human healthy and diseased states. The dynamic signaling that occurs between the host and microbiome is critical for the maintenance of host homeostasis. Analyzing the human microbiome with metaproteomics, metabolomics, and integrative multi‐omics analyses can provide significant information on markers for healthy and diseased states, allowing for the eventual creation of microbiome‐targeted treatments for diseases associated with dysbiosis. Metaproteomics enables functional activity information to be gained from the microbiome samples, while metabolomics provides insight into the overall metabolic states affecting/representing the host–microbiome interactions. Combining these functional ‐omic platforms together with microbiome composition profiling allows for a holistic overview on the functional and metabolic state of the microbiome and its influence on human health. Here the benefits of metaproteomics, metabolomics, and the integrative multi‐omic approaches to investigating the gut microbiome in the context of human health and diseases are reviewed.     

阴道微生物组：种群特征与疾病干预治疗

高通量测序技术的发展显著加快了对人类微生物组的理解。将人体微生物组与疾病关联,力求阐明疾病的发生进程,是推进个性化精准医疗的重要研究方向。近年来,栖居于女性阴道的微生物菌群日益受到关注,发现其生态失调与疾病发生、演变密不可分。文中综述了阴道微生物组与生殖道疾病发生、进展和治疗的最新进展,同时对阴道微生物组培养组、益生菌工程化改造以及合成菌群在阴道微生物组学研究以及疾病干预与治疗方面的前景进行了展望。     

Progress of analytical tools and techniques for human gut microbiome research

Massive DNA sequencing studies have expanded our insights and understanding of the ecological and functional characteristics of the gut microbiome. Advanced sequencing technologies allow us to understand the close association of the gut microbiome with human health and critical illnesses. In the future, analyses of the gut microbiome will provide key information associating with human individual health, which will help provide personalized health care for diseases. Numerous molecular biological analysis tools have been rapidly developed and employed for the gut microbiome researches; however, methodological differences among researchers lead to inconsistent data, limiting extensive share of data. It is therefore very essential to standardize the current methodologies and establish appropriate pipelines for human gut microbiome research. Herein, we review the methods and procedures currently available for studying the human gut microbiome, including fecal sample collection, metagenomic DNA extraction, massive DNA sequencing, and data analyses with bioinformatics. We believe that this review will contribute to the progress of gut microbiome research in the clinical and practical aspects of human health.     

Experimental and analytical tools for studying the human microbiome

The human microbiome substantially affects many aspects of human physiology, including metabolism, drug interactions and numerous diseases. This realization, coupled with ever-improving nucleotide sequencing technology, has precipitated the collection of diverse data sets that profile the microbiome. In the past 2 years, studies have begun to include sufficient numbers of subjects to provide the power to associate these microbiome features with clinical states using advanced algorithms, increasing the use of microbiome studies both individually and collectively. Here we discuss tools and strategies for microbiome studies, from primer selection to bioinformatics analysis.     

肠道微生物与结直肠癌

结直肠癌(colorectal cancer, CRC)是最常见的恶性肿瘤之一,严重威胁着人类健康。肠道微生态作为人体内最复杂、最庞大的微生态系统,与CRC密切相关。CRC患者的肠道微生物群落多样性构成能调节CRC疾病的发生与发展。本综述旨在讨论CRC肠道微生物群的构成、微生物群相关致癌机制、微生物群作为CRC生物标志物的潜力,为临床应用肠道菌群治疗CRC提供新策略与新思路。     

Contrasting Strategies: Human Eukaryotic Versus Bacterial Microbiome Research

Most discussions of human microbiome research have focused on bacterial investigations and findings. Our target is to understand how human eukaryotic microbiome research is developing, its potential distinctiveness, and how problems can be addressed. We start with an overview of the entire eukaryotic microbiome literature (578 papers), show tendencies in the human‐based microbiome literature, and then compare the eukaryotic field to more developed human bacterial microbiome research. We are particularly concerned with problems of interpretation that are already apparent in human bacterial microbiome research (e.g. disease causality, probiotic interventions, evolutionary claims). We show where each field converges and diverges, and what this might mean for progress in human eukaryotic microbiome research. Our analysis then makes constructive suggestions for the future of the field.     

Experimental design and quantitative analysis of microbial community multiomics

Studies of the microbiome have become increasingly sophisticated, and multiple sequence-based, molecular methods as well as culture-based methods exist for population-scale microbiome profiles. To link the resulting host and microbial data types to human health, several experimental design considerations, data analysis challenges, and statistical epidemiological approaches must be addressed. Here, we survey current best practices for experimental design in microbiome molecular epidemiology, including technologies for generating, analyzing, and integrating microbiome multiomics data. We highlight studies that have identified molecular bioactives that influence human health, and we suggest steps for scaling translational microbiome research to high-throughput target discovery across large populations.     

Overview of the rules of the microbial engagement in the gut microbiome: a step towards microbiome therapeutics

Human gut microbiome is a diversified, resilient, immuno-stabilized, metabolically active and physiologically essential component of the human body. Scientific explorations have been made to seek in-depth information about human gut microbiome establishment, microbiome functioning, microbiome succession, factors influencing microbial community dynamics and the role of gut microbiome in health and diseases. Extensive investigations have proposed the microbiome therapeutics as a futuristic medicine for various physiological and metabolic disorders. A comprehensive outlook of microbial colonization, host–microbe interactions, microbial adaptation, commensal selection and immuno-survivability is still required to catalogue the essential genetic and physiological features for the commensal engagement. Evolution of a structured human gut microbiome relies on the microbial flexibility towards genetic, immunological and physiological adaptation in the human gut. Key features for commensalism could be utilized in developing tailor-made microbiome-based therapy to overcome various physiological and metabolic disorders. This review describes the key genetics and physiological traits required for host–microbe interaction and successful commensalism to institute a human gut microbiome.     

人类微生物组产业发展态势及建议

近年来,各国政府、高校、企业和公众高度关注人类微生物组与健康研究,旨在全面系统地解析微生物组的结构和功能,以及生理调控机制,为解决健康问题提供新思路,相关研究带动了人类微生物组行业内益生菌、益生元类保健食品和膳食补充剂、粪菌移植产业的发展,也催生了微生物组检测及健康指导、微生态药物产业的崛起。通过梳理全球人类微生物组产业现状,分析相关产业发展面临的主要瓶颈及未来发展方向,并针对中国人类微生物组产业提出了具体的发展建议。     

人类微生物组测序与比较研究

人体微生物群系影响人类的健康,与人类的各种疾病,如肥胖、糖尿病、冠心病、结肠癌等的发生具有密切的关系.近年来,人类微生物组研究日益受到重视.综述人类微生物组的测序和比较研究进展.     

肠道菌群与肾脏疾病相关性研究进展

人体是一个有机的整体,不同系统之间存在着相互影响。近年来,随着科学的不断发展,肠道菌群与人体健康的关系也逐渐受到重视。肠道菌群虽然居住于肠道,但其作用已经不仅仅局限于消化系统。通过对人体代谢和免疫功能的影响,肠道菌群对人体产生的作用是全身性的。肾脏是体内代谢产物排泄的主要器官,也是免疫复合物沉积的重要部位。因此,肠道菌群在肾脏疾病发展和治疗中都起着至关重要的作用。现如今,两者的关系已经成为科学研究的热点话题。本文总结了近5年的文献,从中西医的角度,针对肠道菌群与肾脏疾病之间的相互关系作一综述。     

Antibiotics and the resistant microbiome

Since the discovery and clinical application of antibiotics, pathogens and the human microbiota have faced a near continuous exposure to these selective agents. A well-established consequence of this exposure is the evolution of multidrug-resistant pathogens, which can become virtually untreatable. Less appreciated are the concomitant changes in the human microbiome in response to these assaults and their contribution to clinical resistance problems. Studies have shown that pervasive changes to the human microbiota result from antibiotic treatment and that resistant strains can persist for years. Additionally, culture-independent functional characterization of the resistance genes from the microbiome has demonstrated a close evolutionary relationship between resistance genes in the microbiome and in pathogens. Application of these techniques and novel cultivation methods are expected to significantly expand our understanding of the interplay between antibiotics and the microbiome.     

Clinicians’ views and expectations of human microbiome science on asthma and its translations

Human microbiome science examines the microbiota that live in and on the human body and their role in human health. This paper examines clinicians’ views and expectations of microbiome science in asthma care. Drawing on qualitative interviews with 10 clinicians in Canada, we explore their perspectives for insights into translation of human microbiome science. The emphasis on novelty in much microbiome scholarship, we suggest, does not account fully for the ways in which microbiome science translations may be taken up in multiple ways that are both disruptive to and continuous with contemporary biomedicine. We suggest that clinicians drew on scientific discourses of “evidence” and “facts” as a form of boundary work to re-establish a separation between western biomedicine and alternative health practitioners, and clinical expertise and lay knowledge. We conclude with a discussion of human microbiome science and the emergence of post-Pasteurian modes of health in western biomedicine.     

Integrating '-omics' and natural product discovery platforms to investigate metabolic exchange in microbiomes

The microbiome is an abundance of microorganisms within a host (e.g. human microbiome). These microorganisms produce small molecules and metabolites that have been shown to affect and dictate the physiology of an individual. Functional knowledge of these molecules, often produced for communication or defense, will reveal the interplay between microbes and host in health and disease. The vast diversity in structure and function of microbiome-associated small molecules necessitate tools that will utilize multiple '-omics' strategies to understand the interactions within the human microbiome. This review discusses the importance of these investigations and the integration of current '-omics' technologies with tools established in natural product discovery in order to identify and characterize uncharacterized small molecules in the effort towards diagnostic modeling of the human microbiome.     

非人灵长类肠道微生物研究进展与展望

肠道微生物组被誉为动物的“第二套基因组”,与动物的个体发育、营养获取、生理功能、免疫调节等重要活动密切相关。非人灵长类在生态位、社会结构、地理分布以及进化上与人类相近,开展其肠道微生物研究不仅有助于了解灵长类的生态、保护和进化,而且对深入了解肠道微生物在人类进化中所发挥的作用也具有重要的参考价值。本文总结了影响非人灵长类肠道微生物变化的因素,包括系统发育、觅食、栖息地破碎化、年龄和性别、圈养方式以及社群生活,并探讨了肠道微生物研究在非人灵长类生态、行为、保护以及适应性进化方面的应用。未来,非人灵长类肠道微生物研究将为灵长类生态、进化和人类健康的研究提供新的视角,为灵长类的保护提供新的理论基础和研究方法。     

基于机器学习的肠道菌群数据建模与分析研究综述

人体肠道菌群与人类的健康和疾病存在密切关系,对肠道菌群的宏基因组数据进行建模和分析,在疾病预测及诊断相关领域科学研究和社会应用方面均具有重要意义。本文从大数据分析和机器学习的角度,对人体肠道菌群数据的建模、分析和预测算法的原理、过程以及典型研究应用实例进行综述,以期推动肠道菌群分析相关研究发展以及探索结合机器学习算法进行肠道菌群分析的有效方式,同时也为开发基于肠道菌群数据的新型诊疗手段提供借鉴,推动我国精准医疗事业发展。     

Composition and stability of the vervet monkey milk microbiome

The human milk microbiome is vertically transmitted to offspring during the postnatal period and has emerged as a critical driver of infant immune and metabolic development. Despite this importance in humans, the milk microbiome of nonhuman primates remains largely unexplored. This dearth of comparative work precludes our ability to understand how species‐specific differences in the milk microbiome may differentially drive maternal effects and limits how translational models can be used to understand the role of vertically transmitted milk microbes in human development. Here, we present the first culture‐independent data on the milk microbiome of a nonhuman primate. We collected milk and matched fecal microbiome samples at early and late lactation from a cohort of captive lactating vervet monkeys (N = 15). We found that, similar to humans, the vervet monkey milk microbiome comprises a shared community of taxa that are universally present across individuals. However, unlike in humans, this shared community is dominated by the genera Lactobacillus, Bacteroides, and Prevotella. We also found that, in contrast to previous culture‐dependent studies in humans, the vervet milk microbiome exhibits greater alpha‐diversity than the gut microbiome across lactation. Finally, we did not find support for the translocation of microbes from the gut to the mammary gland within females (i.e., “entero‐mammary pathway”). Taken together, our results show that the vervet monkey milk microbiome is taxonomically diverse, distinct from the gut microbiome, and largely stable. These findings demonstrate that the milk microbiome is a unique substrate that may selectively favor the establishment and persistence of particular microbes across lactation and highlights the need for future experimental studies on the origin of microbes in milk.     

Proceedings from the 3rd International Conference on Microbiome Engineering

The human microbiome has been inextricably linked to multiple facets of human physiology. From an engineering standpoint, the ability to precisely control the composition and activity of the microbiome holds great promise for furthering our understanding of disease etiology and for new avenues of therapeutic and diagnostic agents. While the field of microbiome research is still in its infancy, growing engineering efforts are emerging to enable new studies in the microbiome and to rapidly translate these findings to microbiome-based interventions. At the 3rd International Conference on Microbiome Engineering, leading experts in the field presented state-of-the-art work in microbiome engineering, discussing probiotics, prebiotics, engineered microbes, microbially derived biomolecules, and bacteriophage.     

The human microbiome: at the interface of health and disease

Interest in the role of the microbiome in human health has burgeoned over the past decade with the advent of new technologies for interrogating complex microbial communities. The large-scale dynamics of the microbiome can be described by many of the tools and observations used in the study of population ecology. Deciphering the metagenome and its aggregate genetic information can also be used to understand the functional properties of the microbial community. Both the microbiome and metagenome probably have important functions in health and disease; their exploration is a frontier in human genetics.     

Application of ecological and evolutionary theory to microbiome community dynamics across systems

A fundamental aim of microbiome research is to understand the factors that influence the assembly and stability of host-associated microbiomes, and their impact on host phenotype, ecology and evolution. However, ecological and evolutionary theories applied to predict microbiome community dynamics are largely based on macroorganisms and lack microbiome-centric hypotheses that account for unique features of the microbiome. This special feature sets out to drive advancements in the application of eco-evolutionary theory to microbiome community dynamics through the development of microbiome-specific theoretical and conceptual frameworks across plant, human and non-human animal systems. The feature comprises 11 research and review articles that address: (i) the effects of the microbiome on host phenotype, ecology and evolution; (ii) the application and development of ecological and evolutionary theories to investigate microbiome assembly, diversity and stability across broad taxonomic scales; and (iii) general principles that underlie microbiome diversity and dynamics. This cross-disciplinary synthesis of theoretical, conceptual, methodological and analytical approaches to characterizing host–microbiome ecology and evolution across systems addresses key research gaps in the field of microbiome research and highlights future research priorities.