Gut microbiota and liver diseases

Several studies revealed that gut microbiota are associated with various human diseases,e.g.,metabolic diseases,allergies,gastroenterological diseases,and liver diseases.The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein,and the liver-gut axis is important to understand the pathophysiology of several liver diseases,especially non-alcoholic fatty liver disease and hepatic encephalopathy.Moreover,gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis.Based on theseprevious findings,trials using probiotics have been performed for the prevention or treatment of liver diseases.In this review,we summarize the current understanding of the changes in gut microbiota associated with various liver diseases,and we describe the therapeutic trials of probiotics for those diseases.     

Gut microbiota and allergic diseases in children

The gut microbiota resides in the human gastrointestinal tract, where it plays an important role in maintaining host health. The human gut microbiota is established by the age of 3 years. Studies have revealed that an imbalance in the gut microbiota, termed dysbiosis, occurs due to factors such as cesarean delivery and antibiotic use before the age of 3 years and that dysbiosis is associated with a higher risk of future onset of allergic diseases. Recent advancements in next-generation sequencing methods have revealed the presence of dysbiosis in patients with allergic diseases, which increases attention on the relationship between dysbiosis and the development of allergic diseases. However, there is no unified perspective on the characteristics on dysbiosis or the mechanistic link between dysbiosis and the onset of allergic diseases. Here, we introduce the latest studies on the gut microbiota in children with allergic diseases and present the hypothesis that dysbiosis characterized by fewer butyric acid-producing bacteria leads to fewer regulatory T cells, resulting in allergic disease. Further studies on correcting dysbiosis for the prevention and treatment of allergic diseases are warranted.     

肠道菌群和心血管疾病的免疫调节

心血管疾病是人类健康的第一杀手,发病率和死亡率逐年增加。数万亿微生物寄居于人类肠道,在心血管疾病及其相关的代谢、免疫反应中发挥着至关重要的作用。先天性和适应性免疫机制都参与了心血管疾病的发生发展,菌群组分和代谢产物可调节巨噬细胞、淋巴细胞等免疫细胞的分化及功能,并通过循环系统影响机体免疫稳态。本文将通过肠道菌群及其代谢产物与免疫系统的相互作用,讨论肠道菌群与心血管疾病发展之间潜在的免疫机制,为预防和治疗心血管疾病提供新思路。     

RETRACTED ARTICLE: The porphyrias: pathophysiology

Porphyrias are a group of inherited and acquired metabolic disorders due to a defect in haem biosynthesis. An enzymatic defect at different steps of haem synthesis leads to tissue accumulation and excessive excretion of porphyrins and/or their toxic precursors. The specific patterns of accumulation determine the variety of clinical manifestations, ranging from acute neurovisceral attacks to skin lesions and liver disease. Most enzyme defects represent partial deficiencies, while familial cases are linked to autosomal or recessive traits. The incomplete penetrance of the genetic defects often requires the triggering or aggravating effect of host-related or environmental factors. While genetics has a role in confirming clinical suspicion and in family screening, biochemical and clinical studies are still central in the diagnosis.     

Gut microbiota mediated molecular events and therapy in liver diseases

Gut microbiota is a community of microorganisms that reside in the gastrointestinal tract. An increasing number of studies has demonstrated that the gut-liver axis plays a critical role in liver homeostasis. Dysbiosis of gut microbiota can cause liver diseases, including nonalcoholic fatty liver disease and alcoholic liver disease. Preclinical and clinical investigations have substantiated that the metabolites and other molecules derived from gut microbiota and diet interaction function as mediators to cause liver fibrosis, cirrhosis, and final cancer. This effect has been demonstrated to be associated with dysregulation of intrahepatic immunity and liver metabolism. Targeting these findings have led to the development of novel preventive and therapeutic strategies. Here, we review the cellular and molecular mechanisms underlying gut microbiota-mediated impact on liver disease. We also summarize the advancement of gut microbiota-based therapeutic strategies in the control of liver diseases.     

Gut microbiota and IBD

Gut microbiota contains about 10(14) bacterial cells classified within 4 bacterial phyla, namely Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. Much of the information has been generated through the application of nucleic acid-based methodologies (16S rRNA) which provide a cornerstone of microbial taxonomy. Inflammatory bowel disease (IBD) involves a dysregulated immune response to the gut microbiota in genetically predisposed hosts. Experimental animal models of colitis provide the best evidence that bacteria present in the bowel of the animals have an essential role in the pathogenesis of colitis since in most models, germ-free animals do not develop disease. Moreover, in the immunodeficient mouse model of colitis called TRUC (T-bet-/- x RAG2-/-), a colitogenic gut microbiota is selected and can be transmitted to mice with intact immunity and induce colitis. Current interest therefore focuses on the bacterial community as the source of antigens that fuel the chronic inflammation seen in IBD. Dysbiosis, an imbalance between harmful and protective bacteria, has been evoked and investigated in IBD. Thus, besides the classical pathogens, gut microbiota can drive pathogenicity via two mechanisms: an expansion of 'pro-inflammatory' species or a restriction in the protective compounds of the microbiota. Complexity of the microbiota suggests that both mechanisms may contribute to chronic gut inflammation in IBD.     

肠道菌群与卒中

近年来提出的"肠-脑轴"理论指出,肠道菌群与中枢神经系统疾病之间存在相互影响.大量研究表明,肠道菌群与抑郁症、帕金森病、阿尔茨海默病之间均存在联系.肠道菌群与卒中的联系亦受到关注.文章对肠道菌群与卒中的关系进行了综述.     

Gut microbiota and obesity

Right ventricular dysfunction during acute pulmonary embolism (PE) predisposes to hemodynamic instability and cardiogenic shock. Aim of this case–control study was to determine the clinical, historical and diagnostic findings associated with right ventricular dysfunction in patients with acute PE involving the main or segmental pulmonary arteries (central PE) and without hemodynamic instability on admission to the Emergency Department (ED) (non-massive PE). From January 1, 2002 to December 31, 2005, 211 patients with central PE were admitted to the Department of Emergency Medicine of the “Antonio Cardarelli” Hospital (Naples, Italy). One hundred eighteen of them had echocardiographic evidence of right ventricular dysfunction on admission to the ED. A history of type 2 diabetes mellitus and chronic obstructive pulmonary disease were significantly associated with an increased risk of this PE-related complication. Compared to patients without right ventricular dysfunction, those with right ventricular dysfunction showed higher levels of markers of cardiac damage, and a significant impairment of respiratory function. Echocardiographic evidence of right ventricular dysfunction on admission to the ED was significantly associated with the occurrence of hemodynamic instability and cardiogenic shock during the PE clinical course. The study results indicate that a history of type 2 diabetes mellitus and chronic obstructive pulmonary disease are significantly associated with the occurrence of right ventricular dysfunction in patients with non-massive and central PE independent of age, gender and other historical and clinical variables detectable on admission to the ED.     

Gut microbiota and obesity

The human gut hosts more than 100 trillion microorganisms, encompassing thousands of species. In adults, Bacteroidetes and Firmicutes are the most prevalent phyla. Experimental data in animal and observational studies in obese patients suggest that obesity is associated with substantial changes in the composition and metabolic function of the gut microbiota. The initial findings linked obesity with the decreased relative proportion of Bacteroidetes to Firmicutes. There are some authors who suggest that probiotics and prebiotics can modulate obesity-host metabolism in obesity and obesity-related disorders.     

Gut in diseases： Physiological elements and their clinical significance

The intestinal barrier function of GI tract is very important in the body except for the function of digestion and absorption. The functional status of gut barrier basically reflects the stress severity when body suffers from trauma and various stimulations. Many harmful factors such as drugs, illnesses, trauma and burns can damage the gut barrier, which can lead to the barrier dysfunction and bacterial/endotoxin translocation. The paper discusses and reviews the concepts, anatomy, pathophysiology of gut barrier and its clinical relations.     

Gut microbiota in common elderly diseases affecting activities of daily living

Gut microbiota are involved in the development or prevention of various diseases such as type 2 diabetes,fatty liver, and malignancy such as colorectal cancer,breast cancer and hepatocellular carcinoma. Alzheimer'sdisease, osteoporosis, sarcopenia, atherosclerotic stroke and cardiovascular disease are major diseases associated with decreased activities of daily living(ADL), especially in elderly people. Recent analyses have revealed the importance of gut microbiota in the control of these diseases. The composition or diversity of these microbiota is different between patients with these conditions and healthy controls, and administration of probiotics or prebiotics has been shown effective in the treatment of these diseases. Gut microbiota may affect distant organs through mechanisms that include regulating the absorption of nutrients and/or the production of microbial metabolites, regulating and interacting with the systemic immune system, and translocating bacteria/bacterial products through disrupted mucosal barriers.Thus, the gut microbiota may be important regulators in the development of diseases that affect ADL. Although adequate exercise and proper diet are important for preventing these diseases, their combination with interventions that manipulate the composition and/or diversity of gut microbiota could be a promising strategy for maintaining health condition and preserving ADL. This review thus summarizes current understanding of the role of gut microbiota in the development or prevention of diseases closely associated with the maintenance of ADL.     

肠道菌群与肾移植

了解肾移植受者肠道菌群的构成及其变化对改善肾移植受者短期及长期预后具有重要的意义。现有研究显示肾移植受者存在肠道菌群失调的情况,特别是出现并发症时,通过改善肾移植受者肠道菌群失调来提高患者预后具有治疗前景。本文旨在阐述肠道菌群在肾移植的最新研究进展。     

Gut microbiota and hepatic encephalopathy

There is a strong relationship between liver and gut; while the portal venous system receives blood from the gut, and its contents may affect liver functions, liver in turn, affects intestinal functions through bile secretion. There is robust evidence that the pathogenesis of hepatic encephalopathy (HE) is linked to alterations in gut microbiota and their by-products such as ammonia, indoles, oxindoles, endotoxins, etc. In the setting of intestinal barrier and immune dysfunction, these by-products are involved in the pathogenesis of complications of liver cirrhosis including HE and systemic inflammation plays an important role. Prebiotics, probiotics and synbiotics may exhibit efficacy in the treatment of HE by modulating the gut flora. They improve derangement in flora by decreasing the counts of pathogenic bacteria and thus improving the endotoxemia, HE and the liver disease. Current evidence suggest that the trials evaluating the role of probiotics in the treatment of HE are of not high quality and all trials had high risk of bias and high risk of random errors. Therefore, the use of probiotics for patients with HE cannot be currently recommended. Further RCTs are required. This review summarizes the main literature findings about the relationships between gut flora and HE, both in terms of the pathogenesis and the treatment of HE.     

Gut microbiota and metabolic syndrome

Symbiosis is the result of the relationship between gut microbiota and human surfaces; in fact, it regulates many functions such as metabolic and protective ones. It is widely known that any changes in the microbes in gut microbiota (dysbiosis) and the regulation of mucosal and systemic host’s immunity have been linked to different diseases such as metabolic syndromes and associated disorders. Recent studies report an aberrant gut microbiota and an alteration of gut microbial metabolic activities in obese subjects, with an important influence of a number of human physiological functions. Most studies suggest that diet, especially the high-fat low-fiber western-style diet, dramatically impacts on gut microbiota composition and functions in those patients with metabolic syndrome. A deeper knowledge of a specific microbiota profile associated with increased risk of metabolic disease and its subsequent modification induced by prebiotics, probiotics or targeted antibiotics will be necessary for the development of new therapeutic approaches in the treatment of metabolic disease.     

肠道菌群与胰岛素抵抗

IR是T2DM的重要特征,也是代谢性疾病的共同病理基础.肠道菌群与机体能量代谢密切相关,且与IR、肥胖和糖尿病发生存在关联.本文就肠道菌群与IR的相互关系作一概述.     

Gut microbiota and liver disease

Microbes are present in large numbers in each human being, in particularly in the gastrointestinal (GI) tract, and have long been believed to have some beneficial effects for their hosts. Till recently, however, we lacked tools for studying these organisms. Rapid technological advances in recent years have markedly improved our understanding of their role both in health and disease. Recent literature suggests that organisms in the GI tract, referred to collectively as gut microbiota, play an indispensable role in the maintenance of host's homeostasis. Alterations in the gut microbiota, that is in the nature and relative density of various constituent bacterial species, appear to have a role in pathogenesis and progression of several GI and hepatic diseases. This has also opened the vista for tinkering with gut flora in an attempt to treat or prevent such diseases. In this review, we have tried to summarize information on normal gut microbiota, laboratory techniques and animal models used to study it, and the role of its perturbations in some of the common hepatic disorders, such as non‐alcoholic fatty liver disease (including obesity), non‐alcoholic steatohepatitis, alcoholic liver disease, and liver cirrhosis and its complications.     

Gut microbiota and GLP-1

A large body of evidence suggests that the regulation of energy balance and glucose homeostasis by fermentable carbohydrates induces specific changes in the gut microbiota. Among the mechanisms, our research group and others have demonstrated that the gut microbiota fermentation (i.e., bacterial digestion of specific compounds) of specific prebiotics or other non-digestible carbohydrates is associated with the secretion of enteroendocrine peptides, such as the glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), produced by L-cells. In this review, we highlight past and recent results describing how dietary manipulation of the gut microbiota, using nutrients or specific microbes, can stimulate GLP-1 secretion in rodents and humans. Furthermore, the purpose of this review is to discuss the putative mechanisms by which specific bacterial metabolites, such as short chain fatty acids, trigger GLP-1 secretion through GPR41/43-dependent mechanisms. Moreover, we conclude by discussing the molecular advance showing that the endocannabinoid system or related bioactive lipids modulated by the gut microbiota may contribute to the regulation of glucose, lipid and energy homeostasis.