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。     

人体肠道病毒组的研究进展

人体肠道微生物包括细菌、真菌、古细菌和病毒等，肠道病毒组的基因组约占肠道微生物总DNA的5.8%，病毒的数量在所有肠道微生物中排名第二，且多样性高。受高比例细菌基因组的影响，很难直接从宏基因组数据中深入分析肠道病毒组。随着病毒样颗粒（VLPs）富集技术的出现以及高通量测序技术的迅速发展，近年来对肠道病毒组的研究越来越多。基于VLPs，发现真核病毒、植物相关病毒和噬菌体是肠道病毒组的主要组成部分，而且未知病毒序列占比高达81%～93%。现阶段病毒组富集扩增方法主要有超速离心、单引物扩增和多重置换扩增等。疾病特异性研究表明，炎症性肠病、酒精性肝病和2型糖尿病等与饮食及肠道病毒组改变相关。本综述回顾了近十年对人类肠道病毒组的研究，总结归纳了目前肠道病毒组的构成、研究方法及与人体健康的相关性，探讨了未来肠道病毒组的研究方向，力求为后续的研究提供新思路。     

肠道微生物与人体健康研究进展

人类肠道中定居着许多对宿主有益的微生物,包括细菌、病毒、真核生物等,它们在肠道内能与其他微生物及免疫系统相互作用,对人体健康具有重要影响,被称为"被遗忘的器官",它们的基因组也被誉为人类的"第二基因组",与人体的能量代谢及物质代谢有关。本文总结了人体肠道中病毒、真核生物、细菌和宿主免疫系统的相互作用,微生物群的失衡可能导致的疾病如肥胖和克罗恩病等,以及微生物环境在人体内的成熟过程,期望有助于诊断和治疗与肠道微生物失衡相关的疾病。     

肠道菌群对肠道病毒感染的影响

肠道病毒(enterovirus)作为危害婴幼儿健康的主要病原体之一,给世界各国带来沉重的医疗和经济负担。近年来,随着对肠道菌群研究的不断深入,越来越多的证据表明,肠道菌群在肠道病毒感染过程中发挥着重要作用。本文就肠道菌群对肠道病毒感染的影响及其相关机制作一综述,为深入开展肠道病毒感染的防控研究提供参考。     

肠道菌群与免疫的相关性研究

由大量微生物构成的复杂微生物群落栖息在人体的肠道内,这些微生物统称作肠道菌群。肠道菌群在人体的消化吸收、免疫、生物拮抗、抗肿瘤等各项生命活动中发挥着重要的作用。近年来的许多研究提示,肠道内复杂的微生物群落和人体的免疫系统间存在着极为密切的关系。免疫系统发挥正常的功能及建立免疫的稳态与肠道菌群的作用密不可分。研究表明肠道菌群能阻止致病微生物入侵从而影响肠道免疫系统,同时还能影响全身免疫系统,在人体的自身免疫性疾病中有较为重要的作用。     

儿童重症手足口病肠道菌群和肠道黏膜通透性的研究进展

手足口病是由肠道病毒引起的儿童常见的传染病,有研究显示肠道病毒进人消化道后在肠黏膜内复制繁殖并持续释放到血液而发病,肠道黏膜是病毒人侵和增殖的主要场所。肠道菌群能防御感染和增强肠道屏障功能,肠道屏障功能在防御外源性和内源性感染方面发挥重要作用,同时在维持肠道免疫稳定和平衡方面也有重要的作用。益生菌是指数量适当时对宿主健康有利的活微生物,有研究报道益生菌在辅助治疗手足口病上是有效的。开展这方面的研究,对于探索手足口病的发病机制和益生菌防治手足口病有十分重要的意义。     

呼吸道病毒和呼吸道、肠道菌群的相互作用

随着新技术的应用,人们对人体不同部位的微生态系统有了进一步的认识,其中的微生物部分不仅指细菌还包括病毒。病毒的存在可以影响呼吸道和肠道菌群变化,同样呼吸道和肠道菌群状态也影响着病毒对人体的入侵程度。本研究就呼吸道和肠道菌群与呼吸道病毒相互作用关系的研究进展作一综述。     

糖尿病皮肤感染与微生物菌群关系的研究进展

糖尿病是以血糖升高为特征的内分泌疾病,由于高血糖状态,使吞噬细胞的趋化作用、吞噬作用以及杀菌功能受损,抗感染能力减弱。正常情况下,人体皮肤微生物菌群对维持人体健康发挥着重大屏障作用,并在皮肤表面保持着动态的平衡,而这种平衡因糖尿病被打破导致皮肤菌群发生紊乱时,人体就会患上各种皮肤感染性疾病,包括真菌、细菌、病毒等。探究如何调整糖尿病患者皮肤微生态平衡、预防及控制其感染,减少感染并发症具有重要意义。     

斑马鱼肠道微生物的研究进展

肠道微生物作为人体重要的"微生物器官",在人体发育、肠道屏障、免疫调节、营养物质消化吸收、毒素排出、血管生成,以及疾病的发生、发展等方面发挥着巨大的作用。脊椎动物生物模型斑马鱼因其各系统发育与人类相应系统有许多共同特点,且具有胚胎透明、发育快速、肠道易于取样等优势,故成为研究肠道微生物的理想模型。然而在国内关于斑马鱼肠道微生物的研究尚处于起步阶段。文章总结了斑马鱼中肠道微生物的相关功能、肠道微生物群落的构建及其演替规律及肠道微生物结构的影响因素,为研究肠道微生物对人类健康的影响及其在疾病治疗中的应用前景提供理论依据。     

人类免疫缺陷病毒感染与肠道菌群的变化研究进展

人类免疫缺陷病毒(HIV)感染CD4~+T细胞,造成免疫系统功能紊乱,导致适应性免疫和固有免疫均发生异常。肠道是人体重要的CD4~+T细胞库,因此,肠道也是病毒感染的主要目标,此外,人肠道内居住着数以亿计的微生物,近年来发现这些微生物群在人类健康中起关键作用。HIV感染除了直接改变肠道CD4~+T细胞组成,也改变了肠道微生物的组成和功能。本文综述了HIV引起的肠道微生物改变,并探讨这些改变在HIV感染个体中产生的局部及系统效应与相关的系统病理损伤,以及用肠道微生物进行靶向调节HIV感染和相关治疗的研究进展。     

肠道菌群与乙型肝炎病毒感染相关肝病的研究进展

乙型肝炎病毒(hepatitis B virus, HBV)可引起人体急性或慢性感染,甚至导致肝硬化或肝癌,其作用机制目前仍未完全阐明。近年来,肠-肝轴受到广泛关注,肠道微生态的相关研究迅速发展,越来越多的实验结果表明,肠道菌群(gut microbiota, GM)与HBV相关肝病的发生和发展具有一定关联。GM可能是了解HBV感染发病机制的一个新视角,并为HBV相关疾病的治疗提供新靶点,这将对未来的治疗策略产生积极影响。本文就HBV感染者肠道菌群与乙型肝炎相关肝病的研究进展进行综述。     

Gut microbiota in antiviral strategy from bats to humans:a missing link in COVID-19

Bats are a potential natural reservoir for SARS-CoV-2 virus and other viruses detrimental to humans. Accumulated evidence has shown that, in their adaptation to a flight-based lifestyle, remodeling of the gut microbiota in bats may have contributed to immune tolerance to viruses. This evidence from bats provides profound insights into the potential influence of gut microbiota in COVID-19 disease in humans. Here, we highlight recent advances in our understanding of the mechanisms by which the gut microbiota helps bats tolerate deadly viruses, and summarize the current clinical evidence on the influence of gut microbiota on the susceptibility to SARS-CoV-2 infection and risk of COVID-19 leading to a fatal outcome. In addition, we discuss the implications of gut microbiota-targeted approaches for preventing infection and reducing disease severity in COVID-19 patients.     

Gut microbiota,inflammation, and molecular signatures of host response to infection

Gut microbial dysbiosis has been linked to many noncommunicable diseases. However, little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying host response to infection. Here, we describe the construction of a proteomic risk score based on 20 blood proteomic biomarkers, which have recently been identified as molecular signatures predicting the progression of the COVID-19. We demonstrate that in our cohort of 990 healthy individuals without infection, this proteomic risk score is positively associated with proinflammatory cytokines mainly among older, but not younger, individuals. We further discover that a core set of gut microbiota can accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model and that these gut microbiota features are highly correlated with proinflammatory cytokines in another independent set of 366 individuals. Fecal metabolomics analysis suggests potential amino acid-related pathways linking gut microbiota to host metabolism and inflammation. Overall, our multi-omics analyses suggest that gut microbiota composition and function are closely related to inflammation and molecular signatures of host response to infection among healthy individuals. These results may provide novel insights into the cross-talk between gut microbiota and host immune system.     

Role of the intestinal microbiota in the immunomodulation of influenza virus infection

Prevention and treatment measures against influenza virus infection remain limited, and alternative host protection strategies are badly needed. In this review, we discuss the regulatory role of intestinal microbiota in influenza infections, and present the latest evidence for strategies seeking to harness gut microbiota for the management of influenza infections.     

宿主遗传因素对肠道菌群的影响

随着高通量测序技术的发展,人们逐渐认识到肠道菌群与人类的健康和疾病密切相关,并发现肠道菌群受很多因素的影响。除了研究传统饮食和药物对肠道菌群的改变外,近年来,科学家也开始注重遗传因素在塑造肠道菌群中的作用。遗传因素可决定宿主的饮食偏好、肠道的生理结构、肠道屏障功能和免疫功能等,而这些都直接与肠道菌群相互作用,参与肠道微生态平衡的构建和稳定。因此,在研究肠道菌群与疾病发生相关性的过程中也需要考虑遗传因素的重要性。随着基因敲除、无菌小鼠和菌群移植等实验技术的革新,以及主成分分析、数量性状基因座和全基因组关联性分析等大数据分析手段的提高,科学家能够深入研究宿主遗传基因与肠道菌群之间的关联性,从而证明宿主遗传基因在塑造肠道微生态的过程中具有重要作用。本文将首先简述肠道菌群与疾病发生之间可能存在的联系,然后从多方面综述遗传因素对肠道菌群的影响及主要的研究进展,从而为今后该领域的深入研究提供重要的指导,也为今后预防和治疗疾病提供新思路和新方法。     

Changes of RNA virus infection rates and gut microbiota in young worker Apis mellifera (Hymenoptera: Apidae) of a chalkbrood-infected colony after a pollination task in a greenhouse

Western honey bee (Apis mellifera Linnaeus) populations recently have been in decline worldwide owing not only to colony collapse disorder but also other infectious diseases. The problem is neither decreasing nor has it been resolved. Chalkbrood (Ascosphaera apis, Maassen ex Claussen) is a well-known fungal brood disease that is now found throughout the world, and there are indications that the incidence of chalkbrood may be on the rise. Here, we conducted comparative studies to analyze infection rates of pathogenic RNA viruses and gut microbiota of young worker honey bees in two colonies: a healthy control colony raised in an open field and a test colony showing the chalkbrood symptom after a 2-month pollination task in a strawberry greenhouse. We found that the number of young worker bees with deformed wing virus (DWV) RNA was significantly elevated in the chalkbrood-infected colony, and two kinds of gut γ-proteobacteria, Frischella perrara gen. nov. and Pasteurellaceae bacterium Trm1, were especially increased in DWV-infected animals. These results showed that the DWV infection rates of worker honey bees were enhanced when their brood was infected with chalkbrood disease and that the gut microbiota in worker bees was significantly affected by the virus infection.     

Gut microbiota composition before infection determines the Salmonella super- and low-shedder phenotypes in chicken

Heterogeneity of infection and extreme shedding patterns are common features of animal infectious diseases. Individual hosts that are super-shedders are key targets for control strategies. Nevertheless, the mechanisms associated with the emergence of super-shedders remain largely unknown. During chicken salmonellosis, a high heterogeneity of infection is observed when animal-to-animal cross-contaminations and reinfections are reduced. We hypothesized that unlike super-shedders, low-shedders would be able to block the first Salmonella colonization thanks to a different gut microbiota. The present study demonstrates that (i) axenic and antibiotic-treated chicks are more prone to become super-shedders; (ii) super or low-shedder phenotypes can be acquired through microbiota transfer; (iii) specific gut microbiota taxonomic features determine whether the chicks develop a low- and super-shedder phenotype after Salmonella infection in isolator; (iv) partial protection can be conferred by inoculation of four commensal bacteria prior to Salmonella infection. This study demonstrates the key role plays by gut microbiota composition in the heterogeneity of infection and pave the way for developing predictive biomarkers and protective probiotics.     

肠道菌群与大脑相互作用的研究进展

定植于宿主肠道中的微生物参与了宿主多种生理功能以及相关疾病的发生。一个新的医学研究热点在近年内逐渐被关注,肠道菌群可通过主要由神经—内分泌介导的肠—脑轴(gut-brain axis,GBA)与大脑进行双向式交流。GBA不仅实现了肠道菌群对大脑发育和功能的影响,也促使大脑对肠道菌群结构和多样性的改变成为可能。本文旨在对肠道菌群与大脑相互作用的研究进展作一综述,以期为肠道和大脑功能领域的研究以及重要相关疾病的治疗策略提供理论依据。     

肠道菌群对代谢相关性脂肪肝的影响及运动干预研究进展

大量研究表明,肠道菌群与神经退行性疾病和代谢性疾病等多种疾病的发生和发展息息相关,菌群的种类和数量会受到遗传、饮食习惯、运动等因素的影响。在代谢相关脂肪性肝病中,肠道菌群的部分代谢物通过增加肝脏脂肪变性、改变肠道黏膜通透性等方式对疾病的发展起到促进作用,菌群的种类和数量变化与病情进展的关系也被广泛研究,但是两者发生的先后顺序仍不十分明确。运动可以增加肠道有益菌群的种类和数量,同时改善高脂饮食导致的肠道菌群紊乱,并有效缓解代谢相关脂肪性肝病的病情,肠道菌群也能对机体的运动能力产生影响,但运动是如何通过肠道菌群来改善代谢相关脂肪性肝病的机制尚不十分明确。本文通过综述三者的相互关系来阐述肠道菌群和运动在代谢相关脂肪性肝病中发挥的重要作用。     

Roles of the gut microbiota in severe SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. The pathophysiological mechanisms linking gut dysbiosis and severe SARS-CoV-2 infection are poorly understood, although gut microbiota disorders are related to severe SARS-CoV-2 infections. The roles of the gut microbiota in severe SARS-CoV-2 infection were compared with those in respiratory viral infection, which is an easily understood and enlightening analogy. Secondary bacterial infections caused by immune disorders and antibiotic abuse can lead to dysregulation of the gut microbiota in patients with respiratory viral infections. The gut microbiota can influence the progression of respiratory viral infections through metabolites and the immune response, which is known as the gut–lung axis. Angiotensin-converting enzyme 2 is expressed in both the lungs and the small intestine, which may be a bridge between the lung and the gut. Similarly, SARS-CoV-2 infection has been shown to disturb the gut microbiota, which may be the cause of cytokine storms. Bacteria in the gut, lung, and other tissues and respiratory viruses can be considered microecosystems and may exert overall effects on the host. By referencing respiratory viral infections, this review focused on the mechanisms involved in the interaction between SARS-CoV-2 infections and the gut microbiota and provides new strategies for the treatment or prevention of severe SARS-CoV-2 infections by improving gut microbial homeostasis.