病毒感染对宿主肠道微生态的影响

摘要：肠道菌群对宿主免疫系统的建立和发育起着重要的作用,与宿主的生理、病理等密切相关,对机体抗病毒作用具有一定的影响。病毒感染影响宿主肠道微生物群落,进而影响宿主机体营养物质的代谢及细胞免疫功能。本研究着重综述病毒感染对宿主肠道微生态及免疫的影响。     

动物宿主——肠道微生物代谢轴研究进展

肠道中栖息着数量庞大且复杂多样的微生物菌群,在维持宿主肠道微环境稳态中发挥重要作用。微生物菌群可以利用宿主肠道的营养素,发酵产生代谢产物,与宿主机体形成宿主—微生物代谢轴(host-microbe metabolic axis)。该代谢轴既能影响营养素吸收和能量代谢,又可调控宿主各项生理过程。本文主要阐述宿主-肠道微生物代谢轴的概念、肠-肝轴、肠-脑轴、肠道微生物与宿主肠道代谢轴的互作以及对机体健康的影响。     

肠道菌群昼夜节律与宿主生物节律 相互作用的研究进展

为了适应地球昼夜更替对机体的影响,哺乳动物进化出了一套内在的适应性计时机制,由此形成了生物钟系统(circadian clock)。昼夜节律作为该系统中的重要部分可与机体的代谢过程同步变化[1]。肠道菌群作为与机体共生的生物群落,在肠道功能方面发挥着重要作用。对肠道菌群的昼夜节律性波动以及与宿主生物节律之间的相互作用进行研究有重要意义。本文将着重阐述肠道菌群昼夜节律与宿主生物节律的相互作用,以及这种相互作用对宿主代谢的影响。     

肠道微生物调控宿主食欲的研究进展

肠道微生物与宿主代谢相互作用,可调节机体的生理功能。宿主机体中存在"微生物-肠道-大脑轴",肠道菌群可通过多种途径影响中枢神经系统,进而对宿主摄食等行为产生影响。食物中不易被宿主消化吸收的膳食纤维等营养物质,被肠道微生物发酵可产生多种代谢产物,这些代谢产物作为信号分子可通过不同途径介导中枢神经系统,进而调控宿主食欲。本文主要综述了肠道微生物及其代谢产物对中枢神经系统与宿主食欲的影响及其可能的调控途径与机制,以加深肠道微生物在调控宿主食欲方面的新认识。     

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。     

动物肠道菌群与宿主肠道免疫系统相互作用的研究进展

作为动物机体中最大的免疫器官之一,动物肠道是机体阻止外源病原体入侵的重要防线。动物肠道中定殖的微生物与宿主的营养物代谢,疾病和免疫系统发育等密切相关。该文主要综述了肠道微生物对于维持肠道屏障完整性的作用、诱导机体T、B淋巴细胞的发育和分化的分子机制及与一些代谢类疾病发生的关系等内容。尽管如此,肠道微生物与宿主免疫系统相互作用的机制还有待深入研究。随着免疫学、微生物学及分子生物学等学科的发展,对动物肠道菌群与宿主免疫系统互作机制的研究也得到快速发展,并为临床上预防和治疗人类疾病提供理论支撑。     

肠道微生物多样性与能量代谢调控及肥胖关系的研究进展

肠道微生物与宿主之间相互选择,构成了一个相对稳定的超有机体。宿主基因型和遗传关系影响肠道微生物的生态学特征,而肠道微生物发酵肠道内多糖,为宿主提供可吸收利用的养分,增强肠道对养分吸收的能力。同时,肠道微生物还影响一些转录因子的活性,调控宿主基因的表达,增强宿主甘油三酯的合成和脂肪沉积,减少脂肪酸氧化分解,调控宿主能量代谢。     

病毒诱导机体产生细胞因子及其信号转导的研究进展

病毒感染后,可诱导机体产生许多细胞因子,这些细胞因子在宿主抗病毒反应及病毒感染引起的免疫病理中起着非常重要的作用。有关病毒感染诱导机体产生细胞因子及其信号转导的研究取得了很大的进展,为开发抗病毒新药开辟了新途径。本文介绍了病毒诱导机体产生细胞因子的病毒成分及其主要信号转导途径。     

肠道黏膜免疫与炎症小体的研究进展

肠道是机体消化器官,为机体生命活动提供所需要的营养。肠道免疫系统有独特的功能,在抵抗潜在病原体侵入机体过程中发挥至关重要的作用。炎症小体是机体天然免疫系统中重要的蛋白复合体感受器,参与病原体引起的宿主防御反应,并在维持肠道免疫稳态中发挥关键作用。本文综述了肠道黏膜免疫系统及炎症小体在肠道免疫中的作用。     

蜜蜂肠道菌群定殖研究进展

肠道菌群在其宿主健康中发挥着各种各样的重要功能。蜜蜂是高度社会化的昆虫,其肠道菌群与大多数昆虫明显不同,由兼性厌氧和微好氧的细菌组成,具有高度保守性和专门的核心肠道微生物群。近年来的研究表明,蜜蜂肠道微生物群在代谢、免疫功能、生长发育以及保护机体免受病原体侵袭等方面起着重要作用,并已证实肠道微生物在蜜蜂健康和疾病中起着重要作用,肠道微生物群的破坏对蜜蜂健康会产生不利影响。本文综述了蜜蜂肠道菌群的特征及菌群定殖研究进展,介绍了蜜蜂的日龄、群体、季节等对蜜蜂肠道菌群定殖的影响,探讨了宿主的功能和新陈代谢对肠道菌群的影响。     

Research progress on the regulation mechanism of probiotics on the microecological flora of infected intestines in livestock and poultry

The animal intestine is a complex ecosystem composed of host cells, gut microbiota and available nutrients. Gut microbiota can prevent the occurrence of intestinal diseases in animals by regulating the homeostasis of the intestinal environment. The intestinal microbiota is a complex and stable microbial community, and the homeostasis of the intestinal environment is closely related to the invasion of intestinal pathogens, which plays an important role in protecting the host from pathogen infections. Probiotics are strains of microorganisms that are beneficial to health, and their potential has recently led to a significant increase in studies on the regulation of intestinal flora. Various potential mechanisms of action have been proposed on probiotics, especially mediating the regulation mechanism of the intestinal flora on the host, mainly including competitive inhibition of pathogens, stimulation of the host's adaptive immune system and regulation of the intestinal flora. The advent of high-throughput sequencing technology has given us a clearer understanding and has facilitated the development of research methods to investigate the intestinal microecological flora. This review will focus on the regulation of probiotics on the microbial flora of intestinal infections in livestock and poultry and will depict future research directions.     

Correction of immunity disorders, treatment of intestinal infections and disbiosis in children (clinical review)

Acute viral and bacterial intestinal infections in children provoke the Tn2 immune response, resulting in development of severe and complicated forms of the disease and sustained by the disbiotic disturbances due to unnecessarily prolonged use of antibacterial drugs. Cycloferon, an early inductor of interferon-1 and -2, was shown to be safe and efficient in the complex therapy of the intestinal infections. It promoted generation of the Th2 immune response and decrease of the repeated isolation of the pathogen with normalization of the disease clinical signs. The host intestinal microflora was normalized and the level of the opportunistic organisms decreased.     

Immunomodulatory functions of type I interferons

Interferon-α (IFNα) and IFNβ, collectively known as type I IFNs, are the major effector cytokines of the host immune response against viral infections. However, the production of type I IFNs is also induced in response to bacterial ligands of innate immune receptors and/or bacterial infections, indicating a broader physiological role for these cytokines in host defence and homeostasis than was originally assumed. The main focus of this Review is the underappreciated immunomodulatory functions of type I IFNs in health and disease. We discuss their function in the regulation of innate and adaptive immune responses, the response to bacterial ligands, inflammasome activation, intestinal homeostasis and inflammatory and autoimmune diseases.     

Chronic Trichuris muris Infection Decreases Diversity of the Intestinal Microbiota and Concomitantly Increases the Abundance of Lactobacilli

The intestinal microbiota is vital for shaping the local intestinal environment as well as host immunity and metabolism. At the same time, epidemiological and experimental evidence suggest an important role for parasitic worm infections in maintaining the inflammatory and regulatory balance of the immune system. In line with this, the prevalence of persistent worm infections is inversely correlated with the incidence of immune-associated diseases, prompting the use of controlled parasite infections for therapeutic purposes. Despite this, the impact of parasite infection on the intestinal microbiota, as well as potential downstream effects on the immune system, remain largely unknown. We have assessed the influence of chronic infection with the large-intestinal nematode Trichuris muris, a close relative of the human pathogen Trichuris trichiura, on the composition of the murine intestinal microbiota by 16S ribosomal-RNA gene-based sequencing. Our results demonstrate that persistent T. muris infection dramatically affects the large-intestinal microbiota, most notably with a drop in the diversity of bacterial communities, as well as a marked increase in the relative abundance of the Lactobacillus genus. In parallel, chronic T. muris infection resulted in a significant shift in the balance between regulatory and inflammatory T cells in the intestinal adaptive immune system, in favour of inflammatory cells. Together, these data demonstrate that chronic parasite infection strongly influences the intestinal microbiota and the adaptive immune system. Our results illustrate the complex interactions between these factors in the intestinal tract, and contribute to furthering the understanding of this interplay, which is of crucial importance considering that 500 million people globally are suffering from these infections and their potential use for therapeutic purposes.     

New weapons in the war on worms: identification of putative mechanisms of immune-mediated expulsion of gastrointestinal nematodes

Parasitic nematode infections of humans and livestock continue to impose a significant public health and economic burden worldwide. Murine models of intestinal nematode infection have proved to be relevant and tractable systems to define the cellular and molecular basis of how the host immune system regulates resistance and susceptibility to infection. While susceptibility to chronic infection is propagated by T helper cell type 1 cytokine responses (characterised by production of IL-12, IL-18 and interferon-gamma), immunity to intestinal-dwelling adult nematode worms is critically dependent on a type 2 cytokine response (controlled by CD4+T helper type 2 cells that secrete the cytokines IL-4, IL-5, IL-9 and IL-13). However, the immune effector mechanisms elicited by type 2 cytokines in the gut microenvironment that precipitate worm expulsion have remained elusive. This review focuses on new studies that implicate host intestinal epithelial cells as one of the dominant immune effector cells against this group of pathogens. Specifically, three recently identified type 2 cytokine-dependent pathways that could offer insights into the mechanisms of expulsion of parasitic nematodes will be discussed: (i) the intelectins, a new family of galactose-binding lectins implicated in innate immunity, (ii) the resistin-like molecules, a family of small cysteine-rich proteins expressed by multiple cell types, and (iii) cytokine regulation of intestinal epithelial cell turnover. Identifying how the mammalian immune response fights gastrointestinal nematode infections is providing new insights into host protective immunity. Harnessing these discoveries, coupled with identifying what the targets of these responses are within parasitic nematodes, offers promise in the design of a new generation of anti-parasitic drugs and vaccines.     

A role for IL-22 in the relationship between intestinal helminths,gut microbiota and mucosal immunity

The intestinal tract is home to nematodes as well as commensal bacteria (microbiota), which have coevolved with the mammalian host. The mucosal immune system must balance between an appropriate response to dangerous pathogens and an inappropriate response to commensal microbiota that may breach the epithelial barrier, in order to maintain intestinal homeostasis. IL-22 has been shown to play a critical role in maintaining barrier homeostasis against intestinal pathogens and commensal bacteria. Here we review the advances in our understanding of the role of IL-22 in helminth infections, as well as in response to commensal and pathogenic bacteria of the intestinal tract. We then consider the relationship between intestinal helminths and gut microbiota and hypothesize that this relationship may explain how helminths may improve symptoms of inflammatory bowel diseases. We propose that by inducing an immune response that includes IL-22, intestinal helminths may enhance the mucosal barrier function of the intestinal epithelium. This may restore the mucosal microbiota populations from dysbiosis associated with colitis and improve intestinal homeostasis.     

Physiological changes in the gastrointestinal tract and host protective immunity: learning from the mouse-Trichinella spiralis model

Infection and inflammation in the gastrointestinal (GI) tract induces a number of changes in the GI physiology of the host. Experimental infections with parasites represent valuable models to study the structural and physiological changes in the GI tract. This review addresses research on the interface between the immune system and GI physiology, dealing specifically with 2 major components of intestinal physiology, namely mucin production and muscle function in relation to host defence, primarily based on studies using the mouse-Trichinella spiralis system. These studies demonstrate that the infection-induced T helper 2 type immune response is critical in generating the alterations of infection-induced mucin production and muscle function, and that this immune-mediated alteration in gut physiology is associated with host defence mechanisms. In addition, by manipulating the host immune response, it is possible to modulate the accompanying physiological changes, which may have clinical relevance. In addition to enhancing our understanding of immunological control of GI physiological changes in the context of host defence against enteric infections, the data acquired using the mouse-T. spiralis model provide a basis for understanding the pathophysiology of a wide range of GI disorders associated with altered gut physiology.     

Heligmosomoides polygyrus: a model for chronic gastrointestinal helminthiasis

Establishment of chronic infections and strain-dependent variation in resistance to challenge infections are well-known features of the relationship between mice and the intestinal nematode parasite Heligmosomoides polygyrus. Here, Fernando Monroy and Javier Enriquez examine host responses, immunogenic and nonimmunogenic antigens of the parasite, and parasite immune evasion strategies in this useful laboratory mouse model of nematode parasitism of mammals.     

鱼类肠道微生物与宿主免疫系统相互作用研究进展

鱼类肠道中存在大量微生物,对于维持宿主健康具有重要作用。鱼类免疫系统能够监视并调控肠道微生物组成,维持肠道菌群稳态。同时,鱼类肠道共生微生物调节鱼类免疫系统,抑制病原微生物的过度增殖,保证宿主的健康。本文回顾了鱼类肠道微生物与宿主免疫系统相互作用的研究进展,重点介绍了宿主免疫系统识别肠道微生物、塑造肠道菌群以及益生菌对宿主免疫和肠道菌群的调控等,提出了理想的益生菌应该来自动物自身胃肠道,生产中应谨慎选用非宿主来源的益生菌,以期为推动鱼类肠道功能微生物开发和应用提供理论支撑。