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。     

肺部菌群和肠道菌群及其互作与肺癌发生发展的相关性研究进展

肺部菌群及肠道菌群与肺癌密切相关,研究发现与健康人群相比肺癌患者的肺部及肠道菌群发生失调,即菌群组成结构发生显著改变。随着“肠-肺轴”概念的提出,肺部及肠道菌群在人体内的紧密联系越发受到重视,因此关于肺部及肠道菌群的研究对于阐明肺癌的发生发展机制有重要的指引作用。文中综述了肺癌患者肺部及肠道菌群的组成特点及可能的互作机制,强调了肠-肺轴中免疫系统的重要性,最后总结了肺部及肠道菌群对肺癌临床治疗的影响,并对肺部及肠道菌群可作为肺癌早期诊断与治疗的新颖靶点进行了展望。     

多糖与肠道菌群相互作用及其构效关系研究进展

肠道菌群是一个复杂的生态系统,影响宿主的饮食、疾病发展、药物代谢和免疫系统调节等诸多生理方面。多糖广泛存在于动物、植物及微生物中,具有多种生理活性。肠道菌群与多糖相互作用,消化难以消化的多糖,多糖作为肠道菌群的重要能量来源,促进益生菌增殖。肠道菌群紊乱导致疾病的发生,多糖通过调节肠道菌群改善疾病。随着“人类微生物组计划”的启动和国内外学者对肠道菌群的深入研究,多糖与肠道菌群的关系逐渐清晰,但多糖的结构与肠道菌群之间的关系还有待进一步探究。因此,本文综述了多糖与肠道菌群的相互作用,并通过调节肠道菌群的组成来改善疾病,以及从多糖的分子量、糖苷键、单糖组成三方面探讨多糖与肠道菌群的构效关系,同时对未来研究的方向进行展望,以期为治疗疾病的深入研究提供重要参照和建议。     

肠道菌群和流感病毒感染的相互作用

流感病毒感染可引起肺部损伤甚至引发严重的并发症,因其抗原性易发生变异,所以疫苗难以进行全面防护。而肠道菌群具有促进免疫系统正常发育及调节免疫细胞内稳态的功能。本文综述了肠道菌群与流感病毒的相互作用和影响,从肠道菌群提高人体固有免疫反应、减轻肺部免疫损伤、促使树突状细胞成熟及形成同源异型交叉保护等方面,探讨肠道菌群对流感病毒感染的预防和治疗作用及其机制,旨在为将肠道菌群作为预防治疗疾病手段和潜在的药物靶点提供思路。     

肠道菌群参与宿主免疫应答的作用及机制研究进展

肠道菌群作为动物体内重要的组成部分,能够直接参与机体的免疫调控作用,促进机体免疫系统发育,维持正常免疫功能。同时,免疫系统对肠道菌群又有调控和制约作用。本文主要综述了肠道菌群的组成以及影响肠道菌群变化的因素,系统阐述了肠道菌群与疾病相互作用的机制,总结了肠道菌群在宿主感染与免疫应答中的作用,为开展肠道菌群参与机体免疫应答的机制方面的研究提供新的思路。     

肠道微生态与生命早期健康

肠道微生态是指肠道正常菌群与其宿主之间相互作用、相互影响的统一整体[1]。生命早期一般指自母体妊娠阶段开始算起至出生后2岁内(近1 000天),这段时间的生命生长发育对于整个生命周期至关重要。随着对肠道微生态研究的不断深入,发现生命早期健康肠道微生态的建立对婴儿各系统生长发育至关重要,因各种因素导致的肠道微生态改变或结构异常与生命早期婴儿发生免疫系统、消化系统、内分泌系统等相关疾病息息相关。本研究将综述生命早期肠道微生物来源、健康肠道微生态建立的相关因素及其生理作用,以及因不健全或紊乱的肠道微生态而引起的相关疾病。     

肠道菌群-肠-脑轴与心身疾病的相互关系

心身疾病是由焦虑、抑郁等不良情绪引起机体出现应激反应而导致的躯体性障碍,是生物、心理和社会因素的共同作用导致的心理、生理症状并存的疾病。负性情绪通过引起下丘脑-垂体-肾上腺轴过度活跃产生应激反应,血液皮质醇激素浓度增加进一步影响交感-肾上腺髓质系统导致机体产生应急反应,进而通过作用于自主神经系统来影响内脏活动。生理应激和心理应激引起的负性情绪均可以引起功能性消化道疾病、高血压、糖尿病、性功能障碍等多种心身疾病。近年来,国内外最新研究表明寄居在消化道内的肠道菌群可通过肠道菌群-肠-脑轴这一通路实现与大脑之间的双向交流和相互作用。一方面,情绪变化可以通过激活肠道免疫系统引起肠道菌群的结构改变;另一方面肠道菌群可以通过作用于迷走神经、免疫系统、内分泌系统等多种途径影响大脑的结构和行为变化。因此,肠道菌群-肠-脑轴是肠道菌群与大脑之间双向交流、互相作用的新通路,调整肠道菌群结构有望成为治疗心身疾病的新靶点。     

益生菌的治疗现状与前景以及 对呼吸道有益菌探索的研究进展

益生菌是调节机体微生态失衡的有效途径。肝功能异常影响肠道微生物,慢性肝衰竭、2型糖尿病、动脉粥样硬化相关心血管疾病等与肠道微生态失衡密切相关。同时肠道菌群亦受环境、遗传等复合条件影响,改变菌群组成可能导致疾病的发生发展。提倡益生菌对疾病的预防、治疗、预后,改善机体微环境,提高生命质量。近年来,益生菌、益生元、合生元三方面的研究飞速发展,对肠道益生菌研发已经取得一定成果。呼吸道作为与外界相通的腔道其优势菌群已经有相关报道,但对呼吸道益生菌的探索尚不明确,呼吸道内的优势菌是否可以制成益生菌制剂尚有待研究。     

人肠道菌群与肺癌关系的研究进展

肠道菌群是由不同种类微生物组成的一个大群体,对宿主的代谢、内分泌系统和免疫系统有着较大的影响。近年来大量的研究发现肠道微生物群落结构变化与消化系统疾病、精神疾病、呼吸系统疾病等多种疾病的发生密切相关,其中关于肠道菌群与肺癌的研究发展迅速。在这篇综述中,我们系统地回顾了肠道常见菌群及肠道菌群与肺癌的关系,并探讨了调节肠道菌群在疾病预防和治疗方面的作用,以期能更加全面地了解肠道菌群在肺癌发生发展中的作用,从而为肺癌的预防、诊断及治疗提供新的方向。     

益生菌、益生元和后生元对食物过敏的影响和作用机制

食物过敏(food allergy,FA)的发病率在近二十年来持续上升,已经严重影响患者的生活质量.生命早期接触外源性抗原少而导致的免疫耐受限制是FA的主要原因.微生物-宿主的相互作用与FA密切相关,健康的微生物菌群促进宿主在生命早期建立成熟的免疫系统,减少FA的易感性,因此,改善肠道菌群和调节机体免疫在治疗FA中至关...     

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。     

Long-Lasting Effects of Early-Life Antibiotic Treatment and Routine Animal Handling on Gut Microbiota Composition and Immune System in Pigs

BackgroundIn intensive pig husbandry systems, antibiotics are frequently administrated during early life stages to prevent respiratory and gastro-intestinal tract infections, often in combination with stressful handlings. The immediate effects of these treatments on microbial colonization and immune development have been described recently. Here we studied whether the early life administration of antibiotics has long-lasting effects on the pig’s intestinal microbial community and on gut functionality.Conclusions/SignificanceThe results obtained in this study indicate that early life (day 4 after birth) perturbations have long-lasting effects on the gut system, both in gene expression (day 55) as well as on microbiota composition (day 176). At day 55 high variance was observed in the microbiota data, but no significant differences between treatment groups, which is most probably due to the newly acquired microbiota during and right after weaning (day 28). Based on the observed difference in gene expression at day 55, it is hypothesized that due to the difference in immune programming during early life, the systems respond differently to the post-weaning newly acquired microbiota. As a consequence, the gut systems of the treatment groups develop into different homeostasis.     

A future perspective on neurodegenerative diseases: nasopharyngeal and gut microbiota

Neurodegenerative diseases are considered a serious life‐threatening issue regardless of age. Resulting nerve damage progressively affects important activities, such as movement, coordination, balance, breathing, speech and the functioning of vital organs. Reports on the subject have concluded that neurodegenerative disease can be caused by mutations of susceptible genes, alcohol consumption, toxins, chemicals and other unknown environmental factors. Although several diagnostic techniques can be used to determine aetiologies, the process is difficult and often fails. Research shows that nasopharyngeal and gut microbiota play important roles in brain to spinal cord coordination. However, no conclusive epidemiologic evidence is available on the roles played by respiratory and gut microbiota in the development of neurodegenerative diseases. Thus, understanding the connection between respiratory and gut microbiota and the nervous system could provide information on causal links. The present review describes future perspectives on the role played by nasopharyngeal and gut microbiota in the development of neurodegenerative diseases.     

Microbiota: A Missing Link in The Pathogenesis of Chronic Lung Inflammatory Diseases

Chronic respiratory diseases account for high morbidity and mortality, with asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) being the most prevalent globally. Even though the diseases increase in prevalence, the exact underlying mechanisms have still not been fully understood. Despite their differences in nature, pathophysiologies, and clinical phenotypes, a growing body of evidence indicates that the presence of lung microbiota can shape the pathogenic processes underlying chronic inflammation, typically observed in the course of the diseases. Therefore, the characterization of the lung microbiota may shed new light on the pathogenesis of these diseases. Specifically, in chronic respiratory tract diseases, the human microbiota may contribute to the disease’s development and severity. The present review explores the role of the microbiota in the area of chronic pulmonary diseases, especially COPD, asthma, and CF.     

Review: The development of the gastrointestinal tract microbiota and intervention in neonatal ruminants

The complex microbiome colonizing the gastrointestinal tract (GIT) of ruminants plays an important role in the development of the immune system, nutrient absorption and metabolism. Hence, understanding GIT microbiota colonization in neonatal ruminants has positive impacts on host health and productivity. Microbes rapidly colonize the GIT after birth and gradually develop into a complex microbial community, which allows the possibility of GIT microbiome manipulation to enhance newborn health and growth and perhaps induce lasting effects in adult ruminants. This paper reviews recent advances in understanding how host-microbiome interactions affect the GIT development and health of neonatal ruminants. Following initial GIT microbiome colonization, continuous exposure to host-specific microorganisms is necessary for GIT development and immune system maturation. Furthermore, the early GIT microbial community structure is significantly affected by early life events, such as maternal microbiota exposure, dietary changes, age and the addition of prebiotics, probiotics and synbiotics, supporting the idea of microbial programming in early life. However, the time window in which interventions can optimally improve production and reduce gastrointestinal disease as well as the role of key host-specific microbiota constituents and host immune regulation requires further study.     

Relationship between gut microbiota and development of T cell associated disease

The interplay between the immune response and the gut microbiota is complex. Although it is well-established that the gut microbiota is essential for the proper development of the immune system, recent evidence indicates that the cells of the immune system also influence the composition of the gut microbiota. This interaction can have important consequences for the development of inflammatory diseases, including autoimmune diseases and allergy, and the specific mechanisms by which the gut commensals drive the development of different types of immune responses are beginning to be understood. Furthermore, sex hormones are now thought to play a novel role in this complex relationship, and collaborate with both the gut microbiota and immune system to influence the development of autoimmune disease. In this review, we will focus on recent studies that have transformed our understanding of the importance of the gut microbiota in inflammatory responses.     

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.     

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。     

Neuropathy in COVID-19 associated with dysbiosis-related inflammation

Although COVID-19 affects mainly lungs with a hyperactive and imbalanced immune response, gastrointestinal and neurological symptoms such as diarrhea and neuropathic pains have been described as well in patients with COVID-19. Studies indicate that gut–lung axis maintains host homeostasis and disease development with the association of immune system, and gut microbiota is involved in the COVID-19 severity in patients with extrapulmonary conditions. Gut microbiota dysbiosis impairs the gut permeability resulting in translocation of gut microbes and their metabolites into the circulatory system and induce systemic inflammation which, in turn, can affect distal organs such as the brain. Moreover, gut microbiota maintains the availability of tryptophan for kynurenine pathway, which is important for both central nervous and gastrointestinal system in regulating inflammation. SARS-CoV-2 infection disturbs the gut microbiota and leads to immune dysfunction with generalized inflammation. It has been known that cytokines and microbial products crossing the blood-brain barrier induce the neuroinflammation, which contributes to the pathophysiology of neurodegenerative diseases including neuropathies. Therefore, we believe that both gut–lung and gut–brain axes are involved in COVID-19 severity and extrapulmonary complications. Furthermore, gut microbial dysbiosis could be the reason of the neurologic complications seen in severe COVID-19 patients with the association of dysbiosis-related neuroinflammation. This review will provide valuable insights into the role of gut microbiota dysbiosis and dysbiosis-related inflammation on the neuropathy in COVID-19 patients and the disease severity.     

Modelling the effect of birth and feeding modes on the development of human gut microbiota

The human gut microbiota is transmitted from mother to infant through vaginal birth and breastfeeding. Bifidobacterium, a genus that dominates the infants’ gut, is adapted to breast milk in its ability to metabolize human milk oligosaccharides; it is regarded as a mutualist owing to its involvement in the development of the immune system. The composition of microbiota, including the abundance of Bifidobacteria, is highly variable between individuals and some microbial profiles are associated with diseases. However, whether and how birth and feeding practices contribute to such variation remains unclear. To understand how early events affect the establishment of microbiota, we develop a mathematical model of two types of Bifidobacteria and a generic compartment of commensal competitors. We show how early events affect competition between mutualists and commensals and microbe-host-immune interactions to cause long-term alterations in gut microbial profiles. Bifidobacteria associated with breast milk can trigger immune responses with lasting effects on the microbial community structure. Our model shows that, in response to a change in birth environment, competition alone can produce two distinct microbial profiles post-weaning. Adding immune regulation to our competition model allows for variations in microbial profiles in response to different feeding practices. This analysis highlights the importance of microbe–microbe and microbe–host interactions in shaping the gut populations following different birth and feeding modes.