肠道菌群与肥胖和糖尿病的关系

人的胃肠道内寄居着种类繁多的单细胞微生物,称为肠道菌群.基因、出生方式、婴幼儿喂养模式、抗生素应用、卫生居住条件以及长期的饮食习惯有助于塑造肠道菌群的组成.越来越多的动物和人体研究表明肠道菌群与肥胖和2型糖尿病密切相关.肠道菌群可通过宿主能量代谢、免疫系统及炎性反应等影响代谢综合征及2型糖尿病的发生、发展.干预肠道菌群有可能成为防治肥胖及糖尿病的新靶点.     

肠道菌群与2型糖尿病

研究表明,2型糖尿病患者肠道菌群结构及功能与健康人不同,肠道菌群可能通过干预宿主营养及能量的吸收利用,促进脂肪的合成及存储,引发慢性低度炎性反应等机制影响2型糖尿病的发展.多项针对肠道菌群的治疗措施在2型糖尿病的动物模型和人群研究中开展,表明饮食、运动及药物均可通过干预肠道菌群的结构及功能影响糖尿病的发生和发展.干预肠道菌群可能成为今后糖尿病防治领域的重要手段之一.     

肠道菌群与非消化系统疾病关系的研究进展

肠道菌群由数万亿个微生物组成,正常情况下它们与宿主保持着共生关系,在调节宿主新陈代谢中发挥着重要作用。近年来,肠道菌群在各系统疾病中的作用受到了大量科研工作者的关注,本文就肠道菌群与非消化系统疾病的关系作一概述,为相关疾病的诊治提供更多的理论支持。     

非酒精性脂肪性肝病与肠道菌群失调新观点

非酒精性脂肪性肝病（NAFLD）在世界范围内患病率逐渐升高,“二次打击学说”发病机制已经被认可,但是具体的病理生理学发病机制还不完全清楚。近期,已有大量研究的新观点来解释肠道菌群在 NAFLD 发病机制中的作用,包括调节肠粘膜通透性、低水平炎症反应和免疫平衡,调节饮食胆碱代谢,调节胆汁酸代谢和增加细菌产生的内源性乙醇等。这些因素在分子水平上解释了肠道菌群如何促发 NAFLD 的发生,并进一步诱导其向非酒精性脂肪性肝炎（NASH）进展。     

肠道菌群代谢产物与胰岛素抵抗相关衰老疾病的研究进展

2型糖尿病(T2DM)和阿尔茨海默病(AD)都是与年龄相关的衰老性疾病,二者存在多种共同危险因素.肠道微生物通过多种代谢产物参与胰岛素生理机能的调控过程,在胰岛素抵抗(IR)发生发展中发挥重要的作用.该文从IR的角度,对肠道菌群代谢产物与T2DM及AD发病机制的内在联系作一综述.     

An update on the role of gut microbiota in chronic inflammatory diseases,and potential therapeutic targets

ABSTRACT

Introduction: The human microbiome plays a critical role in human health, having metabolic, protective, and trophic functions, depending upon its’ exact composition. This composition is affected by a number of factors, including the genetic background of the individual, early life factors (including method of birth, length of breastfeeding) and nature of the diet and other environmental exposures (including cigarette smoking) and general life habits. It plays a key role in the control of inflammation, and in turn, its’ composition is significantly influenced by inflammation.

Areas covered: We consider metabolic, protective, and trophic functions of the microbiome and influences through the lifespan from post-partum effects, to diet later in life in healthy older adults, the effects of aging on both its’ composition, and influence on health and potential therapeutic targets that may have anti-inflammatory effects.

Expert commentary: The future will see the growth of more effective therapies targeting the microbiome particularly with respect to the use of specific nutrients and diets personalized to the individual.     

Role of gut microbiota in cardiovascular diseases

The human gut is colonized by a community of microbiota, primarily bacteria,that exist in a symbiotic relationship with the host. Intestinal microbiota-host interactions play a critical role in the regulation of human physiology.Deleterious changes to the composition of gut microbiota, referred to as gut dysbiosis, has been linked to the development and progression of numerous diseases, including cardiovascular disease(CVD). Imbalances in host-microbial interaction impair homeostatic mechanisms that regulate health and can activate multiple pathways leading to CVD risk factor progression. Most CVD risk factors, including aging, obesity, dietary patterns, and a sedentary lifestyle, have been shown to induce gut dysbiosis. Dysbiosis is associated with intestinal inflammation and reduced integrity of the gut barrier, which in turn increases circulating levels of bacterial structural components and microbial metabolites,including trimethylamine-N-oxide and short-chain fatty acids, that may facilitate the development of CVD. This article reviews the normal function and composition of the gut microbiome, mechanisms leading to the leaky gut syndrome, its mechanistic link to CVD and potential novel therapeutic approaches aimed towards restoring gut microbiome and CVD prevention. As CVD is the leading cause of deaths globally, investigating the gut microbiota as a locus of intervention presents a novel and clinically relevant avenue for future research.     

The emerging role of gut microbiota in cardiovascular diseases

There is mounting evidence which suggests the involvement of gut microbiota dysbiosis in the pathogenesis of various cardiovascular diseases (CVD) and associated risk states such as hypertension, type 2 diabetes, obesity and dyslipidaemia, atherosclerosis, heart failure and atrial fibrillation. The current review comprehensively summarizes the various pathogenetic mechanisms of dysbiosis in these conditions and discusses the key therapeutic implications. Further deeper understanding of the pathogenetic links between CVD and gut microbiota dysbiosis can aid in the development of novel microbiota-based targets for the management of CVDs.     

Role of gut microbiota via the gut-liver-brain axis in digestive diseases

The gut-brain axis is a bidirectional information interaction system between the central nervous system(CNS) and the gastrointestinal tract, in which gut microbiota plays a key role. The gut microbiota forms a complex network with the enteric nervous system, the autonomic nervous system, and the neuroendocrine and neuroimmunity of the CNS, which is called the microbiota-gut-brain axis. Due to the close anatomical and functional interaction of the gut-liver axis, the microbiota-gut-liver-brain axis has attracted increased attention in recent years. The microbiota-gut-liver-brain axis mediates the occurrence and development of many diseases, and it offers a direction for the research of disease treatment. In this review, we mainly discuss the role of the gut microbiota in the irritable bowel syndrome, inflammatory bowel disease, functional dyspepsia, non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis and hepatic encephalopathy via the gut-liver-brain axis, and the focus is to clarify the potential mechanisms and treatment of digestive diseases based on the further understanding of the microbiota-gut-liver-brain axis.     

Dietary approach and gut microbiota modulation for chronic hepatic encephalopathy in cirrhosis

Hepatic encephalopathy(HE) is a common and serious neuropsychiatric complication of cirrhosis, acute liver failure, and porto-systemic shunting. HE largely contributes to the morbidity of patients with liver disease, severely affecting the quality of life of both patients and their relatives and being associated with poor prognosis. Its presentation is largely variable, manifesting with a broad spectrum of cognitive abnormalities ranging from subtle cognitive impairment to coma. The pathogenesis of HE is complex and has historically been linked with hyperammonemia. However, in the last years, it has become evident that the interplay of multiple actors, such as intestinal dysbiosis, gut hyperpermeability, and neuroinflammation, is of crucial importance in its genesis. Therefore, HE can be considered a result of a dysregulated gut-liverbrain axis function, where cognitive impairment can be reversed or prevented by the beneficial effects induced by "gut-centric" therapies, such as non-absorbable disaccharides, non-absorbable antibiotics, probiotics, prebiotics, and fecal microbiota transplantation. In this context dietary modifications, by modulating the intestinal milieu, can also provide significant benefit to cirrhotic patients with HE. This review will provide a comprehensive insight into the mechanisms responsible for gut-liver-brain axis dysregulation leading to HE in cirrhosis.Furthermore, it will explore the currently available therapies and the most promising future treatments for the management of patients with HE, with a special focus on the dietary approach.     

Glucose metabolism: Focus on gut microbiota,the endocannabinoid system and beyond

The gut microbiota is now considered as a key factor in the regulation of numerous metabolic pathways. Growing evidence suggests that cross-talk between gut bacteria and host is achieved through specific metabolites (such as short-chain fatty acids) and molecular patterns of microbial membranes (lipopolysaccharides) that activate host cell receptors (such as toll-like receptors and G-protein-coupled receptors). The endocannabinoid (eCB) system is an important target in the context of obesity, type 2 diabetes (T2D) and inflammation. It has been demonstrated that eCB system activity is involved in the control of glucose and energy metabolism, and can be tuned up or down by specific gut microbes (for example, Akkermansia muciniphila). Numerous studies have also shown that the composition of the gut microbiota differs between obese and/or T2D individuals and those who are lean and non-diabetic. Although some shared taxa are often cited, there is still no clear consensus on the precise microbial composition that triggers metabolic disorders, and causality between specific microbes and the development of such diseases is yet to be proven in humans. Nevertheless, gastric bypass is most likely the most efficient procedure for reducing body weight and treating T2D. Interestingly, several reports have shown that the gut microbiota is profoundly affected by the procedure. It has been suggested that the consistent postoperative increase in certain bacterial groups such as Proteobacteria, Bacteroidetes and Verrucomicrobia (A. muciniphila) may explain its beneficial impact in gnotobiotic mice. Taken together, these data suggest that specific gut microbes modulate important host biological systems that contribute to the control of energy homoeostasis, glucose metabolism and inflammation in obesity and T2D.     

Fecal microbiota transplantation in the metabolic diseases: Current status and perspectives

With the development of microbiology and metabolomics, the relationship between the intestinal microbiome and intestinal diseases has been revealed. Fecal microbiota transplantation (FMT), as a new treatment method, can affect the course of many chronic diseases such as metabolic syndrome, malignant tumor, autoimmune disease and nervous system disease. Although the mechanism of action of FMT is now well understood, there is some controversy in metabolic diseases, so its clinical application may be limited. Microflora transplantation is recommended by clinical medical guidelines and consensus for the treatment of recurrent or refractory Clostridium difficile infection, and has been gradually promoted for the treatment of other intestinal and extraintestinal diseases. However, the initial results are varied, suggesting that the heterogeneity of the donor stools may affect the efficacy of FMT. The success of FMT depends on the microbial diversity and composition of donor feces. Therefore, clinical trials may fail due to the selection of ineffective donors, and not to faulty indication selection for FMT. A new understanding is that FMT not only improves insulin sensitivity, but may also alter the natural course of type 1 diabetes by modulating autoimmunity. In this review, we focus on the main mechanisms and deficiencies of FMT, and explore the optimal design of FMT research, especially in the field of cardiometabolic diseases.     

粪菌移植与慢性肝脏疾病

<正>成人胃肠道粘膜表面积达到300 m2,是人体与外界环境发生相互作用最大的区域。在成人胃肠道中定殖着超过1×10~(14)个微生物。各种不同的环境信号和不同的饮食习惯使肠道微生物群产生大量的代谢产物以及脂多糖/内毒素、胆汁酸、短链脂肪酸、三甲胺等物质。肝脏作为肠道营养物质、细菌产物、毒素以及其他各种代谢产物的接受者和过滤者,经受着这些物质的作用,可能造成许多肝脏疾     

人体寄生虫与肠道菌群相互作用的研究进展

人体寄生虫与人和哺乳动物肠道内的共生菌会发生一些重要的相互作用。肠道内寄生虫与肠道菌群的相互作用及产生的潜在影响已有较多报道,然而有些通常并不寄生在肠道内的寄生虫也会对肠道菌群产生影响。本文就人体肠道内和肠道外寄生虫对肠道菌群影响的研究进展作一综述。     

糖尿病微血管并发症患者肠道菌群的特征分析

目的:探讨糖尿病微血管并发症（DMC）患者的肠道菌群特征。方法:选取2019年9月至2020年11月于承德医学院附属医院内分泌科住院治疗的2型糖尿病（T2DM）患者。收集患者年龄、性别、吸烟史、收缩压、舒张压、体重指数（BMI）、糖化血红蛋白（HbA 1c）、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白...     

Change in gut microbiota for eczema: Implications for novel therapeutic strategies

Eczema is one of the most common inflammatory diseases, often constituting a lifelong burden for afflicted individuals. The complex interaction of host genetic and multiple environmental factors contribute to its pathogenesis. A relationship between maladjustment of gut microbiota and eczema has been brought into the light of day in most previous studies. In eczema preclinical models, specific intestinal microbial species have been demonstrated to prohibit or dwindle immune responsiveness, indicating that these strains among commensal gut bacteria may exert either a morbific or phylactic function in eczema progression. As such, oral probiotics can serve as a medicinal approach for eczema therapy. Given that relative scientific work is still at the early stage, only limited data are available in the field. New sequencing techniques have been fortunately performed to gain access to an extended research on the relationship between gut bacterial flora and human diseases. In the current review, we identified the role of intestinal microbiota in the development of eczema and how specific bacterial strains adjust the immune responsiveness in the midst of disease progression. Probiotics as an applicable treatment for eczema were evaluated in other threads as well.     

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。     

Functional analysis of gut microbiota and immunoinflammation in children with autism spectrum disorders

Background and AimsRecent evidence implicates gut microbiota (GM) and immune alterations in autism spectrum disorders (ASD). We assess GM profile and peripheral levels of immunological, neuronal and bacterial molecules in ASD children and controls. Alarmin HMGB1 was explored as a non-invasive biomarker to monitor gastrointestinal (GI) symptoms.MethodsThirty ASD children and 14 controls entered into the study. GM metagenomic analysis was performed for 16 ASD patients and 7 controls. GM functional profile was assessed by GO term analysis. Blood levels of IL-1β, TNFα, TGFβ, IL-10, INFγ, IL-8, lipopolysaccharide, Neurotensin, Sortilin1 and GSSG/GSH ratio were analyzed in all subjects by ELISA. Fecal HMGB1 was analyzed by Western blot.ResultsWe observed a significant decrease in bacterial diversity. Furthermore, 82 GO terms underrepresented in ASD. Four of them pointed at 3,3 phenylpropionate catabolism and were imputable to Escherichia coli (E. coli) group. Serum levels of TNFα, TGFβ, NT, and SORT-1 increased in ASD patients. Fecal levels of HMGB1 correlated with GI sign severity in ASD children.ConclusionsWe suggest that a decrease of E. coli might affect the propionate catabolism in ASD. We report occurrence of peripheral inflammation in ASD children. We propose fecal HMGB1 as a non-invasive biomarker to detect GI symptoms.     

Altered gut microbiota patterns in COVID-19: Markers for inflammation and disease severity

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to a severe respiratory illness and alters the gut microbiota, which dynamically interacts with the human immune system. Microbiota alterations include decreased levels of beneficial bacteria and augmentation of opportunistic pathogens. Here, we describe critical factors affecting the microbiota in coronavirus disease 2019 (COVID-19) patients. These include, such as gut microbiota imbalance and gastrointestinal symptoms, the pattern of altered gut microbiota composition in COVID-19 patients, and crosstalk between the microbiome and the gut-lung axis/gut-brain-lung axis. Moreover, we have illustrated the hypoxia state in COVID-19 associated gut microbiota alteration. The role of ACE2 in the digestive system, and control of its expression using the gut microbiota is discussed, highlighting the interactions between the lungs, the gut, and the brain during COVID-19 infection. Similarly, we address the gut microbiota in elderly or co-morbid patients as well as gut microbiota dysbiosis of in severe COVID-19. Several clinical trials to understand the role of probiotics in COVID-19 patients are listed in this review. Augmented inflammation is one of the major driving forces for COVID-19 symptoms and gut microbiome disruption and is associated with disease severity. However, understanding the role of the gut microbiota in immune modulation during SARS-CoV-2 infection may help improve therapeutic strategies for COVID-19 treatment.