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.     

肠道菌群与动脉粥样硬化的关系

动脉粥样硬化(As)是心血管疾病(CVD)的主要病理基础且其发病机制具有多样性。肠道菌群失调可通过代谢和免疫系统导致代谢失调和炎症反应,导致斑块形成和破裂,细菌感染在As形成和斑块的发展也具有一定的影响。同时肠道菌群失调可改变胆固醇代谢和菌群代谢物如氧化三甲胺(TMAO)、胆汁酸(BAs)和短链脂肪酸(SCFAs)水平影响As发病进程。目前以肠道菌群为靶点治疗As的研究逐渐深入,益生菌、益生元、粪菌移植、中药可能是未来As治疗的潜在方法并使CVD患者获益。     

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.     

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.     

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.     

Alterations of the gut microbiota in coronavirus disease 2019 and its therapeutic potential

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global health. SARS-CoV-2 infects host cells primarily by binding to angiotensin-converting enzyme 2, which is coexpressed in alveolar type 2 cells and gut epithelial cells. It is known that COVID-19 often presents with gastrointestinal symptoms and gut dysbiosis, mainly characterized by an increase in opportunistic pathogens and a decrease in beneficial commensal bacteria. In recent years, multiple studies have comprehensively explored gut microbiota alterations in COVID-19 and highlighted the clinical correlation between dysbiosis and COVID-19. SARS-CoV-2 causes gastrointestinal infections and dysbiosis mainly through fecal-oral transmission and the circulatory and immune pathways. Studies have shown that the gut microbiota and its metabolites can regulate the immune response and modulate antiviral effects. In addition, the gut microbiota is closely related to gastrointestinal symptoms, such as diarrhea, a common gastrointestinal symptom among COVID-19. Therefore, the contribution of the gut microbiota in COVID-19 should not be overlooked. Strategies targeting the gut microbiota via probiotics, prebiotics and fecal microbiota transplantation should be considered to treat this patient population in the future. However, the specific alterations and mechanisms as well as the contributions of gut microbiota in COVID-19 should be urgently further explored.     

肠道菌群与脑-肠轴功能相互影响的研究进展

人体肠道内的菌群参与了许多生理功能的维持和疾病的发生。作为大脑和胃肠道功能相互调节的重要桥梁,脑-肠轴功能的正常发挥是肠道菌群维持稳定的条件。脑-肠轴紊乱可激活肠黏膜免疫,对肠道菌群产生影响,使菌群结构发生改变。反之,肠道菌群结构改变亦会影响神经系统发育,导致脑-肠轴功能紊乱,其中迷走神经和血清代谢物质在脑-肠轴功能的调节中发挥重要作用。本文就肠道菌群与脑-肠轴功能相互影响的研究进展作一综述。     

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.     

Melatonin prevents obesity through modulation of gut microbiota in mice

Excess weight and obesity are severe public health threats worldwide. Recent evidence demonstrates that gut microbiota dysbiosis contributes to obesity and its comorbidities. The body weight‐reducing and energy balancing effects of melatonin have been reported in several studies, but to date, no investigations toward examining whether the beneficial effects of melatonin are associated with gut microbiota have been carried out. In this study, we show that melatonin reduces body weight, liver steatosis, and low‐grade inflammation as well as improving insulin resistance in high fat diet (HFD)‐fed mice. High‐throughput pyrosequencing of the 16S rRNA demonstrated that melatonin treatment significantly changed the composition of the gut microbiota in mice fed an HFD. The richness and diversity of gut microbiota were notably decreased by melatonin. HFD feeding altered 69 operational taxonomic units (OTUs) compare with a normal chow diet (NCD) group, and melatonin supplementation reversed 14 OTUs to the same configuration than those present in the NCD group, thereby impacting various functions, in particular through its ability to decrease the Firmicutes‐to‐Bacteroidetes ratio and increase the abundance of mucin‐degrading bacteria Akkermansia, which is associated with healthy mucosa. Taken together, our results suggest that melatonin may be used as a probiotic agent to reverse HFD‐induced gut microbiota dysbiosis and help us to gain a better understanding of the mechanisms governing the various melatonin beneficial effects.     

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.     

Gut microbiota and obesity: An opportunity to alter obesity through faecal microbiota transplant (FMT)

Obesity is a global pandemic with immense health consequences for individuals and societies. Multiple factors, including environmental influences and genetic predispositions, are known to affect the development of obesity. Despite an increasing understanding of the factors driving the obesity epidemic, therapeutic interventions to prevent or reverse obesity are limited in their impact. Manipulation of the human gut microbiome provides a new potential therapeutic approach in the fight against obesity. Specific gut bacteria and their metabolites are known to affect host metabolism and feeding behaviour, and dysbiosis of this biosystem may lead to metabolic syndrome. Potential therapies to alter the gut microbiota to treat obesity include dietary changes, supplementation of the diet with probiotic organisms and prebiotic compounds that influence bacterial growth, and the use of faecal microbiota transplant, in which gut microbiota from healthy individuals are introduced into the gut. In this review, we examine the growing scientific evidence supporting the mechanisms by which the human gut microbiota may influence carbohydrate metabolism and obesity, and the various possible therapies that may utilize the gut microbiota to help correct metabolic dysfunction.     

Role of gut microbiota-immunity axis in patients undergoing surgery for colorectal cancer: Focus on short and long-term outcomes

Human body is colonized by a huge amount of microorganisms mostly located in the gastrointestinal tract. These dynamic communities, the environment and their metabolites constitute the microbiota. Growing data suggests a causal role of a dysbiotic microbiota in several pathologies, such as metabolic and neurological disorders, immunity dysregulations and cancer, especially the well-studied colorectal cancer development. However, many were preclinical studies and a complete knowledge of the pathogenetic mechanisms in humans is still absent.The gut microbiota can exert direct or indirect effects in different phases of colorectal cancer genesis. For example, Fusobacterium nucleatum promotes cancer through cellular proliferation and some strains of Escherichia coli and Bacteroides fragilis produce genotoxins. However, dysbiosis may also cause a proinflammatory state and the stimulation of a Th17 response with IL-17 and IL-22 secretion that have a pro-oncogenic activity, as demonstrated for Fusobacterium nucleatum. Microbiota has a crucial role in several stages of postoperative course;dysbiosis in fact seems related with surgical site infections and Enterococcus faecalis(and other collagenase-producers microbes) are suggested as a cause of anastomotic leak. Consequently, unbalanced presence of some species, together with altered immune response may also have a prognostic role. Microbiota has also a substantial role in effectiveness of chemotherapy, chemoresistance and in the related side effects. In other words, a complete knowledge of the fine pathological mechanisms of gut microbiota may provide a wide range of new diagnostic tools other than therapeutic targets in the light of tailored medicine.     

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.     

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.

     

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。     

Microbiota and the gut-liver axis: Bacterial translocation,inflammation and infection in cirrhosis

Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota.In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria(i.e.,gram negative species)and a decrease in autochthonous familiae.Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences.We therefore described the features of the complex interaction between gut microbiota and cirrhotic host,the so called“gut-liver axis”,with a particular attention to the acquired risk of bacterial translocation,systemic inflammation and the relationship with systemic infections in the cirrhotic patient.Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis.     

Influence of fermented milk products,prebiotics and probiotics on microbiota composition and health

The gut microbiota is a highly diverse and relative stabile ecosystem increasingly recognized for its impact on human health. The homeostasis of microbes and the host is also referred to as eubiosis. In contrast, deviation from the normal composition, defined as dysbiosis, is often associated with localized diseases such as inflammatory bowel disease or colonic cancer, but also with systemic diseases like metabolic syndrome and allergic diseases. Modulating a gut microbiota dysbiosis with nutritional concepts may contribute to improving health status, reducing diseases or disease symptoms or supporting already established treatments. The gut microbiota can be modulated by different nutritional concepts, varying from specific food ingredients to complex diets or by the ingestion of particular live microorganisms. To underpin the importance of bacteria in the gut, we describe molecular mechanisms involved in the crosstalk between gut bacteria and the human host, and review the impact of different nutritional concepts such as pre-, pro- and synbiotics on the gastrointestinal ecosystem and their potential health benefits. The aim of this review is to provide examples of potential nutritional concepts that target the gut microbiota to support human physiology and potentially health outcomes.     

Intestinal Dysbiosis: A Possible Mechanism of Alcohol-Induced Endotoxemia and Alcoholic Steatohepatitis in Rats

Background:  Clinical and animal data indicate that gut-derived endotoxin and other luminal bacterial products are necessary cofactors for development of alcoholic liver disease (ALD). Although gut leakiness is clearly an important cause of endotoxemia in ALD, it cannot fully explain endotoxemia in all ALD subjects and thus other factors may be involved. One possible factor is a change in gut microbiota composition (dysbiosis). Thus, the aim of our study was to interrogate the gut bacterial microbiota in alcohol-fed rats to see if chronic alcohol consumption affects gut bacteria composition.
Method:  Male Sprague–Dawley rats were given either alcohol or dextrose intragastrically by gavage twice daily for up to 10 weeks. A subgroup of rats was also given either a probiotic (lactobacillus GG) or a prebiotic (oats) by gavage. Ileal and colonic mucosal-attached microbiota composition were interrogated by Length Heterogeneity PCR (LH-PCR) fingerprinting.
Results:  Bacterial microbiota composition in alcohol-fed rats is not different from dextrose-fed rats at weeks 4 and 6. Mucosa-associated microbiota composition in the colon is altered at 10 weeks of daily alcohol gavage. Both LGG and oats prevented alcohol-induced dysbiosis up to 10 weeks of alcohol treatment.
Conclusion:  Daily alcohol consumption for 10 weeks alters colonic mucosa-associated bacterial microbiota composition in rats. Our data showed, for the first time, that daily alcohol consumption can affect colonic microbiome composition and suggest that dysbiosis may be an important mechanism of alcohol-induced endotoxemia. Further studies are needed to determine how dysbiotic microbiota contributes to development of ALD and whether therapeutic interventions targeted towards dysbiotic microbiota can prevent complications of alcoholism like ALD.     

Dysbiosis in gastrointestinal disorders

The recent development of advanced sequencing techniques has revealed the complexity and diverse functions of the gut microbiota. Furthermore, alterations in the composition or balance of the intestinal microbiota, or dysbiosis, are associated with many gastrointestinal diseases. The looming question is whether dysbiosis is a cause or effect of these diseases. In this review, we will evaluate the contribution of intestinal microbiota in obesity, fatty liver, inflammatory bowel disease, and irritable bowel syndrome. Promising results from microbiota or metabolite transfer experiments in animals suggest the microbiota may be sufficient to reproduce disease features in the appropriate host in certain disorders. Less compelling causal associations may reflect complex, multi-factorial disease pathogenesis, in which dysbiosis is a necessary condition. Understanding the contributions of the microbiota in GI diseases should offer novel insight into disease pathophysiology and deliver new treatment strategies such as therapeutic manipulation of the microbiota.     

Relationship between pouch microbiota and pouchitis following restorative proctocolectomy for ulcerative colitis

Restorative proctocolectomy with ileal pouch-anal anastomosis(IPAA)has become the surgical treatment of choice for many patients with medically refractory ulcerative colitis(UC)and familial adenomatous polyposis(FAP).UC patients with IPAA(UC-IPAA)are,nevertheless,susceptible to inflammatory and noninflammatory sequelae such as pouchitis,which is only rarely noted in FAP patients with IPAA.Pouchitis is the most frequent long-term complication of UC-IPAA patients,with a cumulative prevalence of up to 50%.Although the aetiology of pouchitis remains unclear,accumulating evidence suggests that a dysbiosis of the pouch microbiota and an abnormal mucosal immune response are implicated in its pathogenesis.Studies using culture and molecular techniques have detected a dysbiosis of the pouch microbiota in patients with pouchitis.Risk factors,genetic associations,and serological markers suggest that interactions between the host immune response and the pouch microbiota underlie the aetiology of this idiopathic inflammatory condition.This systematic review focuses on the dysbiosis of the microbiota that inhabit the pouch in UC and FAP patients and its interaction with the mucosal immune system.A metaanalysis was not attempted due to the highly heterogeneous microbiota composition and the different detection methods used by the various studies.Although no specific bacterial species,genus,or family has as yet been identified as pathogenic,there is evidence that a dysbiosis characterized by decreased gut microbiota diversity in UC-IPAA patients may,in genetically predisposed subjects,lead to aberrant mucosal immune regulation triggering an inflammatory process.