COPD的下呼吸道微生态研究进展

新一代测序技术的发展,拓展了人类对肺微生物组的认识,下呼吸道微生物组与呼吸系统疾病的关系日益受到关注。下呼吸道微生物组包含平衡的共生菌群和致病菌群,在慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)中,其疾病的严重性、炎症程度或抗生素等治疗因素均会影响肺部微生物群稳态,下呼吸道微生物群落的改变又可能通过操纵炎症或免疫过程,对COPD的病程产生影响。据此,本文通过回顾近年来对COPD下呼吸道微生态的研究,总结了COPD患者的下呼吸道微生态特征及菌群定植情况,探讨下呼吸道微生态与COPD发病机制之间的相关性和治疗对策,希望为COPD的诊断和治疗提供新思路。     

肺微生物组在慢性阻塞性肺疾病中的研究进展CSCD

慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）是一种以持续的呼吸道症状和气流受限为主要特征的异质性疾病。新一代基因测序技术已经证明健康肺部存在庞大的微生物群落。越来越多的研究表明,肺微生物群失调与COPD的发生、急性加重次数及病死率有关。肺微生物可能通过调控炎症或免疫过程参与COPD的发病机制。全面了解肺微生物群在COPD不同阶段的动态变化和微生物与宿主的相互作用,有助于进一步揭示其在COPD发病机制中的作用。本文综述了肺微生物组在COPD中的研究进展,探讨其与COPD进展之间的关系及潜在的机制,以期开发有针对性的治疗方法。     

肠道和呼吸道菌群与肺部疾病的研究新进展

宿主微生物群落对机体局部以及系统免疫的影响已逐渐引起人们的关注,目前发现局部的微生物群落能够对机体远端部位的免疫能力造成影响。肠道和呼吸道菌群稳态对机体免疫系统发育以及抗病原微生物感染至关重要,肠道和呼吸道菌群失衡与炎症性疾病、代谢性疾病以及过敏性疾病密切相关。肠道和呼吸道菌群失衡会通过"肠—肺轴"的相互作用,引起免疫系统改变与急性、慢性肺部疾病的发生。在这篇综述中,我们对肠道微生物和呼吸道微生物在肠-肺轴中发挥作用的研究进展作一总结,并对从微生物角度进行疾病治疗干预的可能性进行分析。     

肺部菌群与呼吸道疾病的相互关系

由于呼吸道黏膜免疫系统具有很好的防御保护作用和强大的清除病原体的能力,过去学术界曾经一度认为健康机体的肺是无菌的。随着不依赖于体外培养的第二代测序技术的发展,关于肺部共生微生物的结构组成及其免疫调节功能的研究越来越受重视。肺部菌群的结构组成与出生方式、饮食结构、生活环境和抗生素使用等多种因素有关,生命早期的肺部菌群的形成和发育会影响全生命周期的呼吸道疾病的发生和发展。肺部菌群通过与宿主免疫系统相互作用调节肺部免疫稳态,还可以与肠道菌群、呼吸道病毒相互作用影响呼吸道感染。因此,干预生命早期肺部菌群的结构组成可以成为预防和控制呼吸道疾病的有效策略和新靶点。     

支气管哮喘与呼吸道微生态关系的研究进展

人体是个巨大的生态系统,各个器官的表面附着大量的微生物,微生物群通过与宿主细胞之间的相互作用来保证机体的正常营养代谢和微生态稳定。长期以来由于呼吸道的生理功能和特性,其微生物菌群的调节作用没有引起足够重视。自“肠-肺轴”的提出,更多学者开始致力于研究呼吸道微生态,并发现一些呼吸道疾病如慢性阻塞性肺疾病、特发性肺纤维化以及支气管哮喘等的发生发展与呼吸道微生态存在一定的关系,这为进一步研究呼吸道疾病,并寻求更好的治疗方式提供新的方向和选择。本文就支气管哮喘与呼吸道微生态之间的作用关系作一综述。     

肠道菌群与急性肺损伤/急性呼吸窘迫综合征的关系

肠道和肺部具备相似的黏膜结构、生理功能和免疫功能。胃肠道和呼吸道黏膜菌群紊乱影响肠道疾病和急性肺损伤/急性呼吸窘迫综合征(acute lung injury/acute respiratory distress syndrome,ALI/ARDS)发展和预后。当肠道微生物群失调时会导致肠道炎症的发生,诱发肠道免疫反应并增加肠黏膜上皮的通透性,细菌及炎症因子经肠-肺轴或其他路径引发肺部疾病,致使组织器官缺血缺氧,造成肺部疾病预后不良。本文将重点关注肠道菌群失调与ALI/ARDS的关系,阐述肠道菌群失调引发的肠道和肺部慢性炎症,为肠道菌群失调引发肺部疾病的原因及其内在机制的研究提供新思路,为后续治疗提供新的线索。     

急性加重期慢性阻塞性肺疾病患者痰色评分与肺部微生物和病情严重程度的相关性CSCD

目的 探讨急性加重期慢性阻塞性肺疾病患者痰色评分与肺部微生物、病情严重程度的相关性。方法 选择2018年3月至2019年9月我院收治的122例急性加重期慢性阻塞性肺疾病患者,根据其痰色评分分为1~2分组(n=30)与3~4分组(n=92),比较两组患者肺部微生物分布、病情严重程度分布、慢性阻塞性肺疾病评估测试(CAT)评分、白细胞(WBC)水平、C反应蛋白(CRP)水平,分析急性加重期慢性阻塞性肺疾病患者痰色评分与肺部微生物、病情严重程度的相关性。结果 3~4分组患者肺部肺炎克雷伯菌、铜绿假单胞菌、金黄色葡萄球菌、肺炎链球菌、草绿色链球菌、白假丝酵母、酵母样真菌、丝状真菌检出率与1~2分组比较差异无统计学意义(均P>0.05)。3~4分组患者鲍曼不动杆菌检出率显著高于1~2分组(P<0.05)。3~4分组患者病情严重程度分布与1~2分组比较差异有统计学意义(P<0.05)。3~4分组患者CAT评分、WBC水平、CRP水平均显著高于1~2分组(均P<0.05)。急性加重期慢性阻塞性肺疾病患者痰色评分与肺炎克雷伯菌、铜绿假单胞菌、金黄色葡萄球菌、肺炎链球菌、草绿色链球菌、白假丝酵母、酵母样真菌、丝状真菌检出率无显著相关性(均P>0.05),而与鲍曼不动杆菌检出率、CAT评分、WBC水平、CRP水平、病情严重程度呈显著相关性(均P<0.05)。结论 痰色评分与急性加重期慢性阻塞性肺疾病患者肺部微生物和病情严重程度关系密切,有望成为临床评价该类患者肺部微生物分布及病情严重程度的方法之一。     

婴幼儿呼吸道微生物群演替研究进展

婴幼儿从出生开始正常呼吸道微生物就无时不刻地进行着演替,最终呼吸系统微生物形成动态平衡。婴幼儿时期是呼吸道微生物群演替的重要时期,也是免疫发育的关键时期,容易受外界因素的影响,这些影响因素包括分娩方式、喂养方式、抗生素、季节、疫苗接种等。研究表明婴幼儿时期的呼吸道微生物的组成和发育会影响微生物群的稳定性,从而影响呼吸道感染和过敏性疾病的发生。现对婴幼儿呼吸道微生物群演替及其影响因素,如分娩方式、喂养方式、抗生素使用、季节、疫苗接种等进行综述。     

肺微生物组与慢性阻塞性肺疾病的研究进展

摘要：慢性阻塞性肺疾病（COPD）是一种慢性炎症性呼吸道疾病,其特征是持续气流受限和肺部炎症反应异常。气道内微生物是COPD恶化的主要原因,并且使气道中的炎症反应持续存在而促成COPD进展,这导致肺功能的进一步损害和巨大的医疗保健成本。近年来随着高通量测序技术的发展和运用,人类肺微生物组的研究逐渐成为热点。大量研究表明,COPD患者肺内存在明显不同的微生物群落,而且与COPD的疾病严重程度及恶化状态有关。肺微生物组学的研究有助于人们更全面地理解COPD患者肺内的微生态系统及其在该病恶化和进展中的作用。本文就肺微生物组在COPD中的研究进展作一综述,并探讨未来的研究前景。     

肠道、肺部菌群直接或通过肠—肺轴对 呼吸系统慢性疾病的影响

人体寄生的微生物与人体为共生关系,数量庞大,并形成不同的微生态系统,影响人体免疫、代谢、内分泌等生理过程。菌群失衡导致微生态紊乱,从而导致相关疾病的发生发展。呼吸系统慢性疾病患者常有肠道菌群和肺部菌群的改变,肠道菌群通过肠-肺轴影响呼吸系统免疫及呼吸系统慢性疾病,肺部菌群的改变导致肺部疾病的同时亦会通过血流引起肠道菌群的变化。近年来随着高通量测序及生物信息学技术的发展,相关研究也越发被重视,本文着重对肠道菌群、肺部菌群通过肠-肺轴或直接在肺部免疫及呼吸系统慢性疾病中所起的作用进行综述。     

Genome‐wide association studies on the phyllosphere microbiome: Embracing complexity in host–microbe interactions

Environmental sequencing shows that plants harbor complex communities of microbes that vary across environments. However, many approaches for mapping plant genetic variation to microbe‐related traits were developed in the relatively simple context of binary host–microbe interactions under controlled conditions. Recent advances in sequencing and statistics make genome‐wide association studies (GWAS) an increasingly promising approach for identifying the plant genetic variation associated with microbes in a community context. This review discusses early efforts on GWAS of the plant phyllosphere microbiome and the outlook for future studies based on human microbiome GWAS. A workflow for GWAS of the phyllosphere microbiome is then presented, with particular attention to how perspectives on the mechanisms, evolution and environmental dependence of plant–microbe interactions will influence the choice of traits to be mapped.     

2020微生物组测序与分析专题序言

微生物是人体、动植物、土壤、沉积物、水体、空气等生境中最重要的生命体。对这些生境中微生物的分析已经成为一项基础的研究技术。微生物组测序与分析作为近年来快速发展的技术,已经在人类健康、环境污染治理、食品工业以及农牧业等领域得到了广泛应用。为了梳理和总结微生物组测序与分析技术的现状、发展状况和应用前景,本专题收录了16篇本领域的论文,分别从样本保存和处理、单菌基因组测序与分析、特殊生境中的微生物组特征分析、微生物组相关数据库和算法以及微生物组测序与分析专家共识等方面,详细介绍了微生物组测序与分析领域的发展态势,为推动我国微生物组测序与分析产业和科研的快速发展、促进微生物组相关产业的良性发展提供必要的参考。     

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.     

Implementation of a Pan-Genomic Approach to Investigate Holobiont-Infecting Microbe Interaction: A Case Report of a Leukemic Patient with Invasive Mucormycosis

Disease can be conceptualized as the result of interactions between infecting microbe and holobiont, the combination of a host and its microbial communities. It is likely that genomic variation in the host, infecting microbe, and commensal microbiota are key determinants of infectious disease clinical outcomes. However, until recently, simultaneous, multiomic investigation of infecting microbe and holobiont components has rarely been explored. Herein, we characterized the infecting microbe, host, micro- and mycobiomes leading up to infection onset in a leukemia patient that developed invasive mucormycosis. We discovered that the patient was infected with a strain of the recently described Mucor velutinosus species which we determined was hypervirulent in a Drosophila challenge model and has a predisposition for skin dissemination. After completing the infecting M. velutinosus genome and genomes from four other Mucor species, comparative pathogenomics was performed and assisted in identifying 66 M. velutinosus-specific putatively secreted proteins, including multiple novel secreted aspartyl proteinases which may contribute to the unique clinical presentation of skin dissemination. Whole exome sequencing of the patient revealed multiple non-synonymous polymorphisms in genes critical to control of fungal proliferation, such as TLR6 and PTX3. Moreover, the patient had a non-synonymous polymorphism in the NOD2 gene and a missense mutation in FUT2, which have been linked to microbial dysbiosis and microbiome diversity maintenance during physiologic stress, respectively. In concert with host genetic polymorphism data, the micro- and mycobiome analyses revealed that the infection developed amid a dysbiotic microbiome with low α-diversity, dominated by staphylococci. Additionally, longitudinal mycobiome data showed that M. velutinosus DNA was detectable in oral samples preceding disease onset. Our genome-level study of the host-infecting microbe-commensal triad extends the concept of personalized genomic medicine to the holobiont-infecting microbe interface thereby offering novel opportunities for using synergistic genetic methods to increase understanding of infectious diseases pathogenesis and clinical outcomes.     

Gut microbiome in tumorigenesis and therapy of colorectal cancer

Colorectal cancer (CRC) is the malignant tumor with the highest incidence in the digestive system, and the gut microbiome plays a crucial role in CRC tumorigenesis and therapy. The gastrointestinal tract is the organ harboring most of the microbiota in humans. Changes in the gut microbiome in CRC patients suggest possible host–microbe interactions, thereby hinting the potential tumorigenesis, which provides new perspective for preventing, diagnosing, or treating CRC. In this review, we discuss the effects of gut microbiome dysbiosis on CRC, and reveal the mechanisms by which gut microbiome dysbiosis leads to CRC. Gut microbiome modulation with the aim to reverse the established gut microbial dysbiosis is a novel strategy for the prevention and treatment of CRC. In addition, this review summarizes that probiotic antagonize CRC tumorigenesis by protecting intestinal barrier function, inhibiting cancer cell proliferation, resisting oxidative stress, and enhancing host immunity. Finally, we highlight clinical applications of the gut microbiome, such as gut microbiome analysis-based biomarker screening and prediction, and microbe modulation-based CRC prevention, treatment enhancement, and treatment side effect reduction. This review provides the reference for the clinical application of gut microbiome in the prevention and treatment of CRC.     

冬季肺炎和哮喘急性加重患儿呼吸道微生物多样性

目的研究冬季肺炎和哮喘患儿呼吸道微生物的多样性。方法选择2017年11月至2018年1月在我院急诊科治疗的确诊为肺炎和哮喘急性加重的患儿159例,其中肺炎患儿102例,哮喘急性加重患儿57例。选择同时期在本院就诊的无呼吸道疾病患儿88例,设为对照组。检测患儿呼吸道微生物分布情况。结果肺炎和哮喘患儿呼吸道微生物多样性增加。肺炎患儿菌群丰度前3位的菌属分别是链球菌属、不动杆菌属、克雷伯菌属。哮喘患儿菌群丰度前3位的分别是嗜血杆菌属、莫拉氏菌属、葡萄球菌属。呼吸道病毒检测结果显示,肺炎患儿检出率前3位的病毒分别是肺炎支原体、呼吸道合胞病毒和副流感病毒3型。哮喘患儿病毒检出率前3位的是柯萨奇病毒、呼吸道合胞病毒和肺炎支原体。肺炎患儿肺炎支原体检出率明显高于哮喘患儿,柯萨奇病毒检出率明显低于哮喘患儿。结论冬季肺炎和哮喘患儿的临床表现和体征较为相似,但是病原微生物检出情况有所不同。病原微生物检出的差异性有助于正确诊断和鉴别儿童肺炎和哮喘。     

Understanding the role of gut microbiome-host metabolic signal disruption in health and disease

There is growing awareness of the importance of the gut microbiome in health and disease, and recognition that the microbe to host metabolic signalling is crucial to understanding the mechanistic basis of their interaction. This opens new avenues of research for advancing knowledge on the aetiopathologic consequences of dysbiosis with potential for identifying novel microbially-related drug targets. Advances in both sequencing technologies and metabolic profiling platforms, coupled with mathematical integration approaches, herald a new era in characterizing the role of the microbiome in metabolic signalling within the host and have far reaching implications in promoting health in both the developed and developing world.     

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.