肠-脑轴与心血管疾病的研究进展

肠道菌群对人体代谢和肠外器官产生广泛的影响。最近研究表明,肠道菌群失调通过多种途径促进心血管疾病的发生和发展。中枢神经系统调节心血管系统,近年来研究发现由肠道菌群及其代谢产物和中枢神经系统构成的肠-脑轴在高血压、心律失常和心力衰竭等心血管疾病的发生和发展中发挥重要作用。目前,肠-脑轴与心血管疾病的详细机制日渐清晰,现就肠道菌群通过肠-脑轴促进心血管疾病的最新研究机制进行综述。     

菌-肠-脑轴与血脑屏障通透性的相关性研究进展

肠道内数量庞大的菌群对宿主的生理病理功能有着不可忽视的影响.研究显示肠道菌群能够通过合成和释放一些重要的神经递质及调节因子来影响中枢神经系统的功能,肠道菌群的紊乱与血脑屏障完整性降低有关.肠道菌群的稳态在预防与治疗神经退行性疾病中有重要意义.本文拟综述血脑屏障完整性与菌-肠-脑轴相关性的最新进展,为从肠道出发治疗神经系统疾病提供新的方向.     

肠道微生物在非酒精性脂肪性肝病发病中的作用

肝脏和肠道不仅解剖学上而且在生物学功能上存在密切联系,即所谓"肠-肝轴"学说,其对某些疾病的影响越来越受到关注,其中肠道菌群在维持肠-肝轴的平衡方面起着重要作用.肠道菌群紊乱、肠道黏膜通透性改变、肠源性内毒素血症,这将破坏肝脏与肠道之间的正常关系进而导致多种肝脏疾病的发生,进而调整肠微生物成为一种治疗或预防慢性肝病的新手段.有研究表明其在非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)的发生发展中起到了重要作用,这里就肠道微生物对NAFLD的作用做一综述.     

迷走神经参与肠易激综合征中肠-脑互动紊乱的研究进展

迷走神经是肠-脑轴的重要组成部分,参与调节肠道运动和分泌,人体情绪反应和免疫应答,以及肠易激综合征（IBS）患者的肠-脑互动紊乱。本文就迷走神经及其功能,肠-脑轴中迷走神经功能异常与IBS发病的关系,以及迷走神经在IBS治疗中的应用等方面作一综述,以期提高对迷走神经功能与IBS中肠-脑互动紊乱关系的认识,了解其潜在治疗方法。     

中药通过调节脑-肠轴改善急性脑卒中后认知功能障碍的研究进展

脑卒中后认知功能障碍(PSCI)是世界范围内高致残和致死性的重大疾病,目前尚无明确有效的治疗方案,其发生机制多与肠道功能紊乱及菌群失调有关。中药可通过调节肠道菌群、脑肠肽、下丘脑-垂体-肾上腺轴等方式改善PSCI的预后。综述中药通过调控脑-肠轴治疗PSCI的作用机制,以期为PSCI的临床治疗提供新思路。     

肠道菌群和缺血性脑卒中的研究进展

肠道菌群作为人的"第二大脑",不仅从免疫、炎症方面影响脑肠轴，而且内分泌、神经、代谢通路等都会调节脑肠轴，从而影响中枢神经系统(CNS)功能如缺血性脑卒中。同时，CNS功能的改变，亦可通过上述作用机制改变肠道菌群的丰度和多态性，影响肠道功能。近年来，越来越多的研究表明，肠道菌群失调可以参与缺血性脑卒中的发生及发展过程，本综述主要就肠道菌群与缺血性脑卒中之间关系的研究进展进行阐述。     

肠道菌群在肠易激综合征中的病理生理作用

肠易激综合征(irritable bowel syndrome,IBS)是一种功能性肠道疾病。其病因是多因素的,如社会心理因素、遗传或环境因素、脑肠轴功能失调、肠道运动障碍、内脏敏感性增高及肠道菌群的改变等。肠道菌群在IBS发病中起重要作用,包括肠道菌群的组成或其代谢活性的变化,激活黏膜免疫和炎症,导致肠道通透性增加和黏膜屏障功能受损,引起肠道感觉运动功能失调和脑肠轴功能紊乱。本文就肠道菌群在IBS的病理生理学上的重要作用作一概述。     

脑-肠轴失调在肠易激综合征发病中作用的研究进展

肠易激综合征(IBS)的发生是多因素共同作用的结果,其发病机制尚未明确。近年来,以脑-肠轴为基础的生物-心理-社会医学模式参与IBS发病的观念被广泛接受。由神经-内分泌-免疫网络介导的脑-肠双向调节通路,在维持中枢神经系统与肠道局部稳态中发挥重要调节作用,其中任一环节异常,都可能导致稳态平衡破坏而诱发IBS。本文就脑-肠轴失调在IBS发生、发展中作用的研究进展作一综述。     

肠-肝轴在非酒精性脂肪性肝病发生和发展中的作用

肠道与肝脏在功能上有着广泛的联系，其相互作用被表述为“肠-肝轴”的概念。肠道菌群紊乱和肠壁通透性增加等通过免疫反应介导，可促进非酒精性脂肪性肝病的发生和发展；相反，应用抗生素、益生元和益生菌等调节肠道菌群，则有益于缓解非酒精性脂肪性肝病的发展。     

肠道微生态变化与非酒精性脂肪性肝病研究进展

由定植于肠道的大量固有菌群、肠道上皮细胞及肠道局部粘膜免疫系统组成了肠道微生态系统。"肝-肠轴"概念的提出为从肠道微生态角度寻找非酒精性脂肪性肝病(NAFLD)的诊疗措施提供了依据。肠道微生态失衡所致的肠道菌群过度生长、肠黏膜通透性改变、免疫功能紊乱、肠源性内毒素血症、效应细胞激活及炎症因子生成等在NAFLD发生发展中发挥了不容忽视的作用。深入研究肠道菌群与NAFLD之间的关系将为NAFLD的预防和治疗提供新靶点。     

Brain-gut-microbiota axis in Parkinson's disease

Parkinson's disease(PD) is characterized by alphasynucleinopathy that affects all levels of the braingut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological,neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding.Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gutmicrobiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.     

The gut microbiome and irritable bowel syndrome: State of art review

Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract, the physiology of which is not very well understood. There are multiple factors and pathways involved in pathogenesis of this entity. Among all, dysmotility, dysregulation of the brain-gut axis, altered intestinal microbiota and visceral hypersensitivity play a major role. Over the last years, research has shown that the type of gut microbiome present in an individual plays a significant role in the pathophysiology of IBS. Multiple studies have consistently shown that subjects diagnosed with IBS have disruption in gut microbiota balance. It has been established that host immune system and its interaction with metabolic products of gut microbiota play an important role in the gastrointestinal tract. Therefore, probiotics, prebiotics and antibiotics have shown some promising results in managing IBS symptoms via modulating the interaction between the above. This paper discusses the various factors involved in pathophysiology of IBS, especially gut microbiota.     

Gut microecological regulation on bronchiolitis and asthma in children: A review

Introduction

Asthma and bronchiolitis in children are considered common clinical problems associated with gut microbiota. However, the exact relationship between gut microbiota and the above-mentioned diseases remains unclear. Here, we discussed recent advances in understanding the potential mechanism underlying immune regulation of gut microbiota on asthma and bronchiolitis in children as well as the role of the gut–lung axis.

Methods

We retrieved and assessed all relevant original articles related to gut microbiota, airway inflammation-induced wheezing in children, and gut–lung axis studies from databases that have been published so far, including PubMed/MEDLINE, Scopus, Google Scholar, China National Knowledge Infrastructure (CNKI) and the Wanfang Database.

Results

The infant period is critical for the development of gut microbiota, which can be influenced by gestational age, delivery mode, antibiotic exposure and feeding mode. The gut microbiota in children with asthma and bronchiolitis is significantly distinct from those in healthy subjects. Gut microbiota dysbiosis is implicated in asthma and bronchiolitis in children. The presence of intestinal disturbances in lung diseases highlights the importance of the gut–lung axis.

Conclusion

Gut microbiota dysbiosis potentially increases the risk of asthma and bronchiolitis in children. Moreover, a deeper understanding of the gut–lung axis with regard to the gut microbiota of children with respiratory diseases could contribute to clinical practice for pulmonary diseases.     

Focus on the gut-brain axis: multiple sclerosis,the intestinal barrier and the microbiome

The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.     

Starring role of toll-like receptor-4 activation in the gut-liver axis

Since the introduction of the term “gut-liver axis”, many studies have focused on the functional links of intestinal microbiota, barrier function and immune responses to liver physiology. Intestinal and extra-intestinal diseases alter microbiota composition and lead to dysbiosis, which aggravates impaired intestinal barrier function via increased lipopolysaccharide translocation. The subsequent increased passage of gut-derived product from the intestinal lumen to the organ wall and bloodstream affects gut motility and liver biology. The activation of the toll-like receptor 4 (TLR-4) likely plays a key role in both cases. This review analyzed the most recent literature on the gut-liver axis, with a particular focus on the role of TLR-4 activation. Findings that linked liver disease with dysbiosis are evaluated, and links between dysbiosis and alterations of intestinal permeability and motility are discussed. We also examine the mechanisms of translocated gut bacteria and/or the bacterial product activation of liver inflammation and fibrogenesis via activity on different hepatic cell types.     

The intestinal microbiome,probiotics and prebiotics in neurogastroenterology

The brain-gut axis allows bidirectional communication between the central nervous system (CNS) and the enteric nervous system (ENS), linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent experimental work suggests that the gut microbiota have an impact on the brain-gut axis. A group of experts convened by the International Scientific Association for Probiotics and Prebiotics (ISAPP) discussed the role of gut bacteria on brain functions and the implications for probiotic and prebiotic science. The experts reviewed and discussed current available data on the role of gut microbiota on epithelial cell function, gastrointestinal motility, visceral sensitivity, perception and behavior. Data, mostly gathered from animal studies, suggest interactions of gut microbiota not only with the enteric nervous system but also with the central nervous system via neural, neuroendocrine, neuroimmune and humoral links. Microbial colonization impacts mammalian brain development in early life and subsequent adult behavior. These findings provide novel insights for improved understanding of the potential role of gut microbial communities on psychological disorders, most particularly in the field of psychological comorbidities associated with functional bowel disorders like irritable bowel syndrome (IBS) and should present new opportunity for interventions with pro- and prebiotics.     

蠕虫及肠道原虫感染与肠道菌群关系研究进展

肠道菌群是人体最大最复杂的生态系统,与肠道病毒和寄生虫等共同栖息在人或动物肠道内。已有研究表明,肠道菌群紊乱与多种疾病的发生、发展及预后密切相关。定植在宿主体内的寄生虫可直接或间接影响肠道菌群及其与机体的相对稳态,而肠道菌群结构及多样性的改变也会影响寄生虫感染及疾病的发生、发展和预后。本文就蠕虫及肠道原虫与肠道菌群相互关系研究进展作一综述。     

Gut microbiota-derived metabolites as key mucosal barrier modulators in obesity

A significant breakthrough in the field of obesity research was the demonstration that an obese phenotype could be manipulated by modulating the gut microbiota. An important next step is to elucidate a human-relevant “map’’ of microbiota-host interactions that regulate the metabolic health of the host. An improved understanding of this crosstalk is a prerequisite for optimizing therapeutic strategies to combat obesity. Intestinal mucosal barrier dysfunction is an important contributor to metabolic diseases and has also been found to be involved in a variety of other chronic inflammatory conditions, including cancer, neurodegeneration, and aging. The mechanistic basis for intestinal barrier dysfunction accompanying metabolic disorders remains poorly understood. Understanding the molecular and cellular modulators of intestinal barrier function will help devise improved strategies to counteract the detrimental systemic consequences of gut barrier breakage. Changes in the composition and function of the gut microbiota, i.e., dysbiosis, are thought to drive obesity-related pathogenesis and may be one of the most important drivers of mucosal barrier dysfunction. Many effects of the microbiota on the host are mediated by microbiota-derived metabolites. In this review, we focus on several relatively well-studied microbial metabolites that can influence intestinal mucosal homeostasis and discuss how they might affect metabolic diseases. The design and use of microbes and their metabolites that are locally active in the gut without systemic side effects are promising novel and safe therapeutic modalities for metabolic diseases.     

Gut microbiota and irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that poses a significant health concern. Although its etiology remains unknown, there is growing evidence that gut dysbiosis is involved in the development and exacerbation of IBS. Previous studies have reported altered microbial diversity, abundance, and composition in IBS patients when compared to controls. However, whether dysbiosis or aberrant changes in the intestinal microbiota can be used as a hallmark of IBS remains inconclusive. We reviewed the literatures on changes in and roles of intestinal microbiota in relation to IBS and discussed various gut microbiota manipulation strategies. Gut microbiota may affect IBS development by regulating the mucosal immune system, brain–gut–microbiome interaction, and intestinal barrier function. The advent of high-throughput multi-omics provides important insights into the pathogenesis of IBS and promotes the development of individualized treatment for IBS. Despite advances in currently available microbiota-directed therapies, large-scale, well-organized, and long-term randomized controlled trials are highly warranted to assess their clinical effects. Overall, gut microbiota alterations play a critical role in the pathophysiology of IBS, and modulation of microbiota has a significant therapeutic potential that requires to be further verified.     

Role of gut microbiota in the pathogenesis and therapeutics of minimal hepatic encephalopathy via the gut-liver-brain axis

Minimal hepatic encephalopathy (MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety; however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.