肠道菌群与缺血性卒中

脑肠轴是中枢神经系统与胃肠道间相互作用的重要通路。缺血性卒中可促进肠道菌群失调和移位,肠道菌群及其代谢产物也会反向影响缺血性卒中的发生、发展及转归。文章对缺血性卒中与肠道菌群的相关文献进行回顾,以综述两者的联系及相关机制,并对靶向肠道菌群的卒中治疗进行了展望。     

肠道菌群及其代谢物在脑卒中后认知障碍发病机制中的研究进展

卒中后认知障碍（PSCI）是卒中后常见的神经精神并发症,严重影响卒中患者的生活质量及预后。近年来,越来越多的研究表明,肠道微生物群与认知障碍疾病存在联系。肠道菌群及其代谢物既可影响神经递质水平,又可介导神经免疫细胞炎症反应或干涉神经元及其信号传导,共同影响大脑功能和认知行为。PSCI发病机制迄今尚未阐明,亦无有效的防治方法。研究表明,肠道微生物群和大脑之间可能会通过微生物群-肠道-大脑轴相互影响,即肠道菌群可以通过神经免疫、神经内分泌以及迷走神经等“双向脑肠信号”与中枢神经系统进行信息交流。     

肠道菌群与1型糖尿病的关系

1型糖尿病发病机制与遗传因素、环境因素及自身免疫因素均有关,是在遗传因素基础上,由环境因素启动,以T淋巴细胞介导的胰岛β细胞进行性损伤为主要特征的自身免疫性疾病.肠道菌群作为环境因素与1型糖尿病发生有直接关系,可通过改变肠壁通透性和宿主免疫系统影响发病.肠道菌群、宿主免疫及1型糖尿病三者之间存在相互联系,研究肠道菌群可为1型糖尿病的预防和治疗提供线索.     

肠道菌群与缺血性卒中相关性的研究进展

《柳叶刀》杂志发表的一项关于全球疾病负担的系统分析表明,卒中于2017年已跃升为中国的首要死因[1]。我国70%的脑卒中为缺血性,为老年人群三大死因之一,也是导致成年人残疾的主要原因,造成沉重的社会负担。肠道菌群被证实与肥胖、糖尿病、高血压病、帕金森病、阿尔兹海默病等多种疾病密切相关[2]。众多研究发现,肠道菌群通过代谢途径和免疫反应作用于人体内环境稳态,影响卒中的发生与发展[3-5]。同样,缺血性卒中的发生引起机体免疫功能降低和肠道内环境改变,导致肠道菌群紊乱,影响卒中预后。因此,肠道菌群对于缺血性卒中的发生、发展及预后具有深远影响。     

肠道菌群与肥胖和2型糖尿病的相关性

近年来研究发现肠道菌群、肥胖、胰岛素抵抗及2型糖尿病之间有着紧密的联系.有证据表明,在宿主的营养、免疫和代谢中有不可替代的作用的肠道菌群不仅可以通过调节宿主脂肪吸收存储相关的基因,影响后者的能量平衡,更重要的是其结构失调导致宿主循环系统中内毒素增加,诱发慢性、低水平炎症,导致肥胖和胰岛素抵抗及糖尿病.肠道菌群影响人体健康已得到初步证明,研究结果表明肠道菌群很可能与肥胖及2型糖尿病的发生发展有密切联系[1],但是究竟是如何联系的呢？我们对此进行如下综述.     

脑中风与胃肠道的关系

介绍肠道菌群在种类和数量等方面的变化及可能参与的神经、体液、免疫代谢,发现肠道菌群影响中枢,故肠道菌群失调可能是促进脑血管疾病发生发展的原因之一。对肠道菌群进行调控有望成为脑血管疾病的潜在治疗新靶点。中医学对脑/神志与胃肠之间的联系早有记载,现从中西医结合角度对脑中风与胃肠道的联系进行综述。     

肠道菌群与骨骼肌消耗症的研究进展

骨骼肌在人体日常活动中发挥重要作用.肿瘤、慢性肾脏病及营养不良等疾病时,由于骨骼肌能量消耗过多,患者最终表现为骨骼肌萎缩.对"肠-肌"轴的研究表明,肠道菌群通过多种途径参与骨骼肌消耗,影响骨骼肌萎缩.肠道菌群与骨骼肌消耗之间的关系,使得通过干预肠道菌群来预防和治疗骨骼肌萎缩成为可能.     

肠道菌群及其代谢物与心律失常关系的研究进展

最近,几项涉及动物和人类的研究表明,心律失常(如心房颤动、室性心律失常和窦房结功能障碍)的发生和发展与肠道菌群的失调及其代谢物之间存在显著的联系。肠道菌群生态系统主要是一个虚拟的内分泌器官,在宿主体内相互作用并对分子信号作出反应。肠道与宿主的相互作用涉及几种生物途径,包括胆汁酸。现综述肠道菌群及其代谢物在心房颤动、室性心律失常和窦房结功能障碍的发生和发展中的作用与机制,以及在心律失常防治方面的潜在价值,以促进心律失常患者疾病的良性转归。     

肠道微环境对TH17细胞分化及其功能影响的研究进展

肠道微环境是指肠道微生态环境,由大量微生物菌群组成并参与机体肠道黏膜保护、能量传递及营养代谢等生理机制,微环境发生改变时会引起肠道病理性反应。人体内肠道菌群失调会影响肠道TH17细胞的正常发育、分化及功能,从而使免疫系统的抗病能力降低,导致肠道黏膜损伤及肠道炎症反应。肠道微环境、肠道菌群、肠道TH17细胞与肠道炎症性反应相关因素之间有密切关系,但目前联系并不明确。本文就肠道微环境、肠道菌群、肠道TH17细胞与肠道炎症反应相关因素之间关系作一概述,从而探讨肠道疾病可能的发病机制,为炎症性肠道疾病治疗途径提供新的思路。     

肠道菌群在结直肠癌中的研究进展

人体肠道菌群是一个复杂的系统,由大量的微生物构成.肠道菌群和人类健康与疾病密切相关,且始终保持着动态平衡.肠道菌群之间相互作用,同时与机体共同维持消化,吸收,代谢等功能.近年来,肠道菌群始终是研究的一大热点,有大量研究表明肠道菌群与结直肠癌的发生发展密切相关.本文就肠道菌群与结直肠癌的关系,发病机制及防治作用进行综述,为结直肠癌的研究提供一些新思路.     

Techniques used to characterize the gut microbiota: a guide for the clinician

The gut microbiota is a complex ecosystem that has a symbiotic relationship with its host. An association between the gut microbiota and disease was first postulated in the early 20(th) century. However, until the 1990s, knowledge of the gut microbiota was limited because bacteriological culture was the only technique available to characterize its composition. Only a fraction (estimated at <30%) of the gut microbiota has been cultured to date. Since the 1990s, advances in culture-independent techniques have spearheaded our knowledge of the complexity of this ecosystem. These techniques have elucidated the microbial diversity of the gut microbiota and have shown that alterations in the gut microbiota composition and function are associated with certain disease states, such as IBD and obesity. These new techniques are fast, facilitate high throughput, identify organisms that are uncultured to date and enable enumeration of organisms present in the gut microbiota. This Review discusses the techniques that can used to characterize the gut microbiota, when they can be applied to human studies and their relative advantages and limitations.     

Characterisation and therapeutic manipulation of the gut microbiome in inflammatory bowel disease

Inflammatory bowel diseases are thought to develop as a result of dysregulation of the relationship that exists between the gut microbiota, host genetics and the immune system. The advent of culture‐independent techniques has revolutionised the ability to characterise the role of the gut microbiota in health and disease based on the microbiota's genetic make‐up. Inflammatory bowel diseases are characterised by dysbiosis which is an imbalance between pro‐ and anti‐inflammatory bacteria and a reduction in bacterial diversity. Emerging data suggest that it is not only the presence of the gut microbiota but the functional activity of the microbiota that appears to play an important role in health and disease. Current strategies to manipulate therapeutically the gut microbiota using dietary modification, prebiotics, probiotics, antibiotics and faecal microbiota transplantation aim to restore the balance to a state of normobiosis. However, the ability of such strategies to correct dysbiosis and thereby achieve therapeutic benefit is yet to be fully characterised.     

Gut microbiota in the pathogenesis of inflammatory bowel disease

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a chronic and relapsing inflammatory disorder of the intestine. Although its incidence is increasing globally, the precise etiology remains unclear and a cure for IBD has yet to be discovered. The most accepted hypothesis of IBD pathogenesis is that complex interactions between genetics, environmental factors, and the host immune system lead to aberrant immune responses and chronic intestinal inflammation. The human gut harbors a complex and abundant aggregation of microbes, collectively referred to as the gut microbiota. The gut microbiota has physiological functions associated with nutrition, the immune system, and defense of the host. Recent advances in next-generation sequencing technology have identified alteration of the composition and function of the gut microbiota, which is referred to as dysbiosis, in IBD. Clinical and experimental data suggest dysbiosis may play a pivotal role in the pathogenesis of IBD. This review is focused on the physiological function of the gut microbiota and the association between the gut microbiota and pathogenesis in IBD. In addition, we review the therapeutic options for manipulating the altered gut microbiota, such as probiotics and fecal microbiota transplantation.     

Lessons from mother: Long-term impact of antibodies in breast milk on the gut microbiota and intestinal immune system of breastfed offspring

From birth to adulthood, the gut microbiota matures from a simple community dominated by a few major bacterial groups into a highly diverse ecosystem that provides both benefits and challenges to the host. Currently there is great interest in identifying environmental and host factors that shape the development of our gut microbiota. Breast milk is a rich source of maternal antibodies, which provide the first source of adaptive immunity in the newborn''s intestinal tract. In this addendum, we summarize our recent data demonstrating that maternal antibodies in breast milk promote long-term intestinal homeostasis in suckling mice by regulating the gut microbiota and host gene expression. We also discuss important unanswered questions, future directions for research in this field, and implications for human health and disease.     

Lessons from mother: Long-term impact of antibodies in breast milk on the gut microbiota and intestinal immune system of breastfed offspring

From birth to adulthood, the gut microbiota matures from a simple community dominated by a few major bacterial groups into a highly diverse ecosystem that provides both benefits and challenges to the host. Currently there is great interest in identifying environmental and host factors that shape the development of our gut microbiota. Breast milk is a rich source of maternal antibodies, which provide the first source of adaptive immunity in the newborn's intestinal tract. In this addendum, we summarize our recent data demonstrating that maternal antibodies in breast milk promote long-term intestinal homeostasis in suckling mice by regulating the gut microbiota and host gene expression. We also discuss important unanswered questions, future directions for research in this field, and implications for human health and disease.     

From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?

Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.

     

An unexplored brain-gut microbiota axis in stroke

Microbiota research, in particular that of the gut, has recently gained much attention in medical research owing to technological advances in metagenomics and metabolomics. Despite this, much of the research direction has focused on long-term or chronic effects of microbiota manipulation on health and disease. In this addendum, we reflect on our recent publication that reported findings addressing a rather unconventional hypothesis. Bacterial pneumonia is highly prevalent and is one of the leading contributors to stroke morbidity and mortality worldwide. However, microbiological cultures of samples taken from stroke patient with a suspected case of pneumonia often return with a negative result. Therefore, we proposed that post-stroke infection may be due to the presence of anaerobic bacteria, possibly those originated from the host gut microbiota. Supporting this, we showed that stroke promotes intestinal barrier breakdown and robust microbiota changes, and the subsequent translocation of selective bacterial strain from the host gut microbiota to peripheral tissues (i.e. lung) induces post-stroke infections. Our findings were further supported by various elegant studies published in the past 12 months. Here, we discuss and provide an overview of our key findings, supporting studies, and the implications for future advances in stroke research.     

Gut brain axis: an insight into microbiota role in Parkinson’s disease

Parkinson's disease (PD) is one of the most common progressive neurodegenerative diseases. It is characterized neuropathologically by the presence of alpha-synuclein containing Lewy Bodies in the substantia nigra of the brain with loss of dopaminergic neurons in the pars compacta of the substantia nigra. The presence of alpha-synuclein aggregates in the substantia nigra and the enteric nervous system (ENS) drew attention to the possibility of a correlation between the gut microbiota and Parkinson’s disease. The gut-brain axis is a two-way communication system, which explains how through the vagus nerve, the gut microbiota can affect the central nervous system (CNS), including brain functions related to the ENS, as well as how CNS can alter various gut secretions and immune responses. As a result, this dysbiosis or alteration in gut microbiota can be an early sign of PD with reported changes in short chain fatty acids, bile acids, and lipids. This gave rise to the use of probiotics and faecal microbiota transplantation as alternative approaches to improve the symptoms of patients with PD. The aim of this review is to discuss investigations that have been done to explore the gastrointestinal involvement in Parkinson’s disease, the effect of dysbiosis, and potential therapeutic strategies for PD.

     

Fecal Microbiota Transplantation in the Treatment of Clostridium difficile Infections

In recent years, Clostridium difficile infections have become more frequent, more severe, more refractory to standard treatment, and more likely to recur. Current antibiotic treatment regimens for Clostridium difficile infection alter the normal gut flora, which provide colonization resistance against Clostridium difficile. Over the past few years, there has been a marked increase in the knowledge of the gut microbiota and its role in health maintenance and disease causation. This has, fortuitously, coincided with the use of a unique microbial replacement therapy, fecal microbiota transplantation, in the treatment of patients with multiple recurrent Clostridium difficile infections. We briefly review current knowledge of the gut microbiota's functions. We then review the indications for use of fecal microbiota transplantation in Clostridium difficile infection, the techniques employed, and results of treatment. Fecal microbiota transplantation has been shown to be efficacious for patients with multiply recurrent Clostridium difficile infections (reported cure rates of 90%), with an excellent short-term safety profile, and has been included in the American College of Gastroenterology treatment guidelines for this troublesome disease.     

Differences in gut microbiota associated with age,sex, and stool consistency in healthy Japanese subjects

Background

Human gut microbiota is involved in host health and disease development. Investigations of age-related and sex-related alterations in gut microbiota are limited, and the association between stool consistency and gut microbiota has not been fully investigated. We investigated gut microbiota differences related to age, sex, and stool consistency in healthy Japanese subjects.

Methods

Two-hundred and seventy-seven healthy Japanese subjects aged 20–89 years were enrolled. Fecal samples were obtained to analyze the gut microbiome. We evaluated the association between stool consistency [Bristol stool scale (BSS)] and gut microbiota.

Results

Although there were significant differences in the microbial structure between males and females, the α-diversity of gut microbiota showed no difference between males and females or among age groups. There were significant increases in genera Prevotella, Megamonas, Fusobacterium, and Megasphaera and Bifidobacterium, Ruminococcus, and Akkermansia in males and females, respectively. The ratio of hard stools (BSS types 1 and 2) was higher in females; the ratio of loose stools (BSS type 6) was higher in males. No younger male had BSS type 1 or type 2. Fusobacterium in males was significantly higher in the loose consistency group, and Oscillospira was significantly higher in the hard consistency group in males; Campylobacter, SMB53, and Turicibacter were significantly higher in the hard consistency group in females.

Conclusions

Several changes in gut microbiota were associated with age and sex. Stool consistency and gut microbiota associations emphasized the importance of stool consistency assessments to understand intestinal function.