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.     

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.     

Microbiota in health and irritable bowel syndrome: current knowledge,perspectives and therapeutic options

Abstract

The gastrointestinal tract is a natural reservoir of microbiota. The gut is germ-free at birth, but rapidly becomes host to various bacteria establishing a progressively mutual relationship. The composition of gut microbiota is individual-specific and depends on the genotype of the host and environmental factors. Novel techniques have been used to characterize gastrointestinal microbiota, including genomic approaches. The bacterial profile shows that dominant and minor phyla are present in the gastrointestinal tract. From the proximal to the distal segments of the gut the bacterial density gradually increases, reaching an estimated 10¹¹ to 10¹² bacteria per gram of colonic content. Dynamic interactions between gut and microbiota play a physiological role in metabolic, protective and structural functions, while dysbiosis contributes to several diseases. Microbiota appear to play a role in IBS, where qualitative and quantitative changes of bacteriaoccur in IBS subtypes. Initial therapeutic approaches in IBS have focused on microbiota. The relationship between perturbations of the microbiota, mucosal inflammation and IBS remains to be further investigated.     

Possible role of intestinal stem cells in the pathophysiology of irritable bowel syndrome

The pathophysiology of irritable bowel syndrome(IBS) is not completely understood. However, several factors are known to play a role in pathophysiology of IBS such as genetics, diet, gut microbiota, gut endocrine cells,stress and low-grade inflammation. Understanding the pathophysiology of IBS may open the way for new treatment approaches. Low density of intestinal stem cells and low differentiation toward enteroendocrine cells has been reported recently in patients with IBS. These abnormalities are believed to be the cause of the low density of enteroendocrine cells seen in patients with IBS.Enteroendocrine cells regulate gastrointestinal motility, secretion, absorption and visceral sensitivity. Gastrointestinal dysmotility, abnormal absorption/secretion and visceral hypersensitivity are all seen in patients with IBS and haven been attributed to the low density the intestinal enteroendocrine cells in these patients.The present review conducted a literature search in Medline(Pub Med) covering the last ten years until November 2019, where articles in English were included.Articles about the intestinal stem cells and their possible role in the pathophysiology of IBS are discussed in the present review. The present review discusses the assumption that intestinal stem cells play a central role in the pathophysiology of IBS and that the other factors known to contribute to the pathophysiology of IBS such as genetics, diet gut microbiota, stress, and lowgrade inflammation exert their effects through affecting the intestinal stem cells.It reports further the data that support this assumption on genetics, diet, gut microbiota, stress with depletion of glutamine, and inflammation.     

Unraveling the ties between irritable bowel syndrome and intestinal microbiota

Irritable bowel syndrome(IBS)is the most prevalent functional gastrointestinal disorder.It is a multifactoria disorder.Intestinal microbiota may cause the pathogenesis of IBS by contributing to abnormal gastrointestina motility,low-grade inflammation,visceral hypersensitivity,communication in the gut-brain axis,and so on.Previous attempts to identify the intestinal microbiota composition in IBS patients have yielded inconsistent and occasionally contradictory results.This inconsistency may be due to the differences in the molecular techniques employed,the sample collection and handling methods,use of single samples that are not linked to fluctuating symptoms,or other factors such as patients diets and phenotypic characterizations.Despite these difficulties,previous studies found that the intestina microbiota in some IBS patients was completely different from that in healthy controls,and there does appear to be a consistent theme of Firmicutes enrichment and reduced abundance of Bacteroides.Based on the differences in intestinal microbiota composition,many studies have addressed the roles of microbiotatargeted treatments,such as antibiotics and probiotics,in alleviating certain symptoms of IBS.This review summarizes the current knowledge of the associations between intestinal microbiota and IBS as well as the possible modes of action of intestinal microbiota in the pathogenesis of IBS.Improving the current level of understanding of host-microbiota interactions in IBS is important not only for determining the role of intestinal microbiota in IBS pathogenesis but also for therapeutic modulation of the microbiota.     

Antibiotics,gut microbiota,and irritable bowel syndrome: What are the relations?

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder in which recurrent abdominal pain is associated with defecation or a change in bowel habits (constipation, diarrhea, or both), and it is often accompanied by symptoms of abdominal bloating and distension. IBS is an important health care issue because it negatively affects the quality of life of patients and places a considerable financial burden on health care systems. Despite extensive research, the etiology and underlying pathophysiology of IBS remain incompletely understood. Proposed mechanisms involved in its pathogenesis include increased intestinal permeability, changes in the immune system, visceral hypersensitivity, impaired gut motility, and emotional disorders. Recently, accumulating evidence has highlighted the important role of the gut microbiota in the development of IBS. Microbial dysbiosis within the gut is thought to contribute to all aspects of its multifactorial pathogenesis. The last few decades have also seen an increasing interest in the impact of antibiotics on the gut microbiota. Moreover, antibiotics have been suggested to play a role in the development of IBS. Extensive research has established that antibacterial therapy induces remarkable shifts in the bacterial community composition that are quite similar to those observed in IBS. This suggestion is further supported by data from cohort and case-control studies, indicating that antibiotic treatment is associated with an increased risk of IBS. This paper summarizes the main findings on this issue and contributes to a deeper understanding of the link between antibiotic use and the development of IBS.     

Comparison of gut microbiota profile in celiac disease,non-celiac gluten sensitivity and irritable bowel syndrome: A systematic review

Gut microbiota is vital for human health. Shifts in the microbial diversity can affect bacterial function, and dysbiosis is associated with a variety of gastrointestinal disorders, including celiac disease (CD) and irritable bowel syndrome (IBS). The distinction between IBS and non-celiac gluten sensitivity (NCGS) is unclear, and it is conceivable that the gut microbiota profile of these patients may overlap. To our knowledge, no existing literature has evaluated the microbial characteristics in CD, IBS, and NCGS. Hence, this systematic review aims to compare the gut microbiota profile in these three diagnoses. A literature search was conducted in PubMed (Medline) until April 2019. Studies investigating bacterial diversity in the gut of patients with CD, IBS, and NCGS were eligible. Inclusion criteria were observational studies and randomized controlled trials reporting bacterial profile at baseline. Ninety-one articles were identified, of which 13 trials were eligible for inclusion. Overall, the bacterial composition of the gut microbiota of patients with CD and those with IBS shared the many similarities. The microbial richness was correspondingly reduced in these patient-groups compared with healthy controls, but this was not reported for NCGS. Our findings suggest that the bacterial profiles of patients with IBS and CD share certain disease-specific trends. Fewer similarities were observed between the bacterial profiles of patients with IBS and NCGS. Notably, the data are limited; thus, no solid conclusions can be made on the basis of these findings alone. The suggested trends can be a valuable basis for further research.     

Gene, environment, and brain-gut interactions in irritable bowel syndrome

The genetic predisposition and influence of environment may underlie in the pathogenesis and/or pathophysiology of irritable bowel syndrome (IBS). This phenomenon, gene x environment interaction together with brain-gut interactions is emerging area to be clarified in IBS research. Earlier studies focused on candidate genes of neurotransmitters, cytokines, and growth factors. Among them, some studies but not all studies revealed association between phenotypes of IBS and 5-hydroxytryptamine (5-HT)-related genes, noradrenaline-related genes, and cytokine genes. Recent prospective cohort study showed that genes encoding immune and adhesion molecules were associated with post-infectious etiology of IBS. Psychosocial stressors and intraluminal factors especially microbiota are keys to develop IBS. IBS patients may have abnormal gut microbiota as well as increased organic acids. IBS is disorder that relates to brain-gut interactions, emotional dysregulation, and illness behaviors. Brain imaging with or without combination of visceral stimulation enables us to depict the detailed information of brain-gut interactions. In IBS patients, thalamus, insula, anterior cingulate cortex, amygdala, and brainstem were more activated in response to visceral stimulation than controls. Corticotropin-releasing hormone and 5-HT are the candidate substances which regulate exaggerated brain-gut response. In conclusion, gene x environment interaction together with brain-gut interactions may play crucial roles in IBS development. Further fundamental research on this issue is warranted.     

Do gut microbial communities differ in pediatric IBS and health?

Human gastrointestinal microbial communities are recognized as important determinants of the host health and disease status. We have recently examined the distal gut microbiota of two groups of children: healthy adolescents and those diagnosed with diarrhea-predominant irritable bowel syndrome (IBS). We have revealed the common core of phylotypes shared among all children, identified genera differentially abundant between two groups and surveyed possible relationships among intestinal microbial genera and phylotypes. In this article we explored the use of supervised and unsupervised ordination and classification methods to separate and classify child fecal samples based on their quantitative microbial profile. We observed sample separation according to the participant health status, and this separation could often be attributed to the abundance levels of several specific microbial genera. We also extended our original correlation network analysis of the relative abundances of bacterial genera across samples and determined possible association networks separately for healthy and IBS groups. Interestingly, the number of significant genus abundance associations was drastically lower among the IBS samples, which can potentially be attributed to the existence of multiple routes to microbiota disbalance in IBS or to the loss of microbial interactions during IBS development.     

Bacteria,genetics and irritable bowel syndrome

Evaluation of: Villani AC, Lemire M, Thabane M et al. Genetic risk factors for post-infectious irritable bowel syndrome following a waterborne outbreak of gastroenteritis. Gastroenterology 138, 1502–1513 (2010).

While the pathogenesis of irritable bowel syndrome (IBS) remains to be fully defined, two clinical observations – the occurrence, de novo, of IBS following bacterial gastroenteritis and the history, commonly obtained from IBS patients, of other instances of the syndrome within their families – have instigated investigations, in IBS, of the potential roles, on the one hand, of the gut microbiota and the host response and, on the other hand, of genetic factors. The study reviewed here relates to both of these factors by studying genetic predisposition to postinfective IBS in a large population of individuals who were exposed to a multimicrobial enteric infection, which resulted in a severe outbreak of gastroenteritis and was followed by the development of IBS in over a third. In this detailed study, the investigators identified a number of genes that were linked significantly to the development of postinfectious-IBS in the Toll-like receptor 9, IL-6 and cadherin 1 regions. These genes play important roles in bacterial recognition, the inflammatory response and epithelial integrity, respectively, and provide considerable support for the hypothesis that links IBS onset to disturbances in the microbiota and the host response.     

Microbiota and viral hepatitis: State of the art of a complex matter

Changes in gut microbiota influence both the gut and liver, which are strictly connected by the so-called “gut–liver axis”. The gut microbiota acts as a major determinant of this relationship in the onset and clinical course of liver diseases. According to the results of several studies, gut dysbiosis is linked to viral hepatitis, mainly hepatitis C virus and hepatitis B virus infection. Gut bacteria-derived metabolites and cellular components are key molecules that affect liver function and modulate the pathology of viral hepatitis. Recent studies showed that the gut microbiota produces various molecules, such as peptidoglycans, lipopolysaccharides, DNA, lipoteichoic acid, indole-derivatives, bile acids, and trimethylamine, which are translocated to the liver and interact with liver immune cells causing pathological effects. Therefore, the existence of crosstalk between the gut microbiota and the liver and its implications on host health and pathologic status are essential factors impacting the etiology and therapeutic approach. Concrete mechanisms behind the pathogenic role of gut-derived components on the pathogenesis of viral hepatitis remain unclear and not understood. In this review, we discuss the current findings of research on the bidirectional relationship of the components of gut microbiota and the progression of liver diseases and viral hepatitis and vice versa. Moreover, this paper highlights the current therapeutic and preventive strategies, such as fecal transplantation, used to restore the gut microbiota composition and so improve host health.     

Gut Microbiota as Potential Orchestrators of Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a multifactorial functional disorder with no clearly defined etiology or pathophysiology. Modern culture-independent techniques have improved the understanding of the gut microbiota’s composition and demonstrated that an altered gut microbiota profile might be found in at least some subgroups of IBS patients. Research on IBS from a microbial perspective is gaining momentum and advancing. This review will therefore highlight potential links between the gut microbiota and IBS by discussing the current knowledge of the gut microbiota; it will also illustrate bacterial-host interactions and how alterations to these interactions could exacerbate, induce or even help alleviate IBS.     

The gut microbiota and metabolic disease: current understanding and future perspectives

The human gut microbiota has been studied for more than a century. However, of nonculture‐based techniques exploiting next‐generation sequencing for analysing the microbiota, development has renewed research within the field during the past decade. The observation that the gut microbiota, as an environmental factor, contributes to adiposity has further increased interest in the field. The human microbiota is affected by the diet, and macronutrients serve as substrates for many microbially produced metabolites, such as short‐chain fatty acids and bile acids, that may modulate host metabolism. Obesity predisposes towards type 2 diabetes and cardiovascular disease. Recently, it has been established that levels of butyrate‐producing bacteria are reduced in patients with type 2 diabetes, whereas levels of Lactobacillus sp. are increased. Recent data suggest that the reduced levels of butyrate‐producing bacteria might be causally linked to type 2 diabetes. Bariatric surgery, which promotes long‐term weight loss and diabetes remission, alters the gut microbiota in both mice and humans. Furthermore, by transferring the microbiota from postbariatric surgery patients to mice, it has been demonstrated that an altered microbiota may contribute to the improved metabolic phenotype following this intervention. Thus, greater understanding of alterations of the gut microbiota, in combination with dietary patterns, may provide insights into how the gut microbiota contributes to disease progression and whether it can be exploited as a novel diagnostic, prognostic and therapeutic target.     

益生菌对大肠癌的防治作用及机制研究进展

大肠癌(colorectal cancer,CRC)是目前最常见的恶性肿瘤之一,CRC的发生及发展与肠道微生态有密切的关系。肠道菌群对于肠道功能的维持及内环境的平衡具有重要作用。肠道菌群失调可通过多种途径促进CRC的发生。益生菌是调节肠道微生态的主要方法,并可通过多种机制发挥抗肿瘤作用。本文综合目前研究进展,从调节肠道代谢产物、保护肠道黏膜屏障完整性、抑制肠道炎症、调节宿主免疫反应、促进凋亡和细胞分化、抑制细胞增殖等方面总结益生菌对癌前病变及CRC的防治作用及机制,为临床肠道微生态的调节及CRC的防治提供指导。     

Mechanisms of gut microbiota-mediated bone remodeling

The mechanisms underlying the systemic effects mediated by gut microbiota are under active investigation. In addition to local, direct effects of gut microbiota on the host, metabolic products from microbiota may act peripherally, reaching distal organs through the circulation. In our recent publication we demonstrated that gut microbiota influence bone remodeling distally, promoting both bone resorption and formation. We proposed that these effects are mediated, at least in part, by the induction of insulin like growth factor (IGF-1) by the microbiota metabolite short chain fatty acids (SCFA). Here we explore additional mechanisms by which microbial metabolites could directly or indirectly alter host bone remodeling. We discuss whether SCFA directly modulate bone resorption by their actions on osteoclasts, and test the possibility that serotonin is another gut microbiota derived long-distance mediator of effects on bone remodeling. A detailed understanding of the mechanisms of microbiota effect on bone remodeling could help establish potential therapeutic strategies to promote bone health.     

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.     

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.     

Effect of commensals and probiotics on visceral sensitivity and pain in irritable bowel syndrome

The last ten years’ wide progress in the gut microbiota phylogenetic and functional characterization has been made evidencing dysbiosis in several gastrointestinal diseases including inflammatory bowel diseases and irritable bowel syndrome (IBS). IBS is a functional gut disease with high prevalence and negative impact on patient’s quality of life characterized mainly by visceral pain and/or discomfort, representing a good paradigm of chronic gut hypersensitivity. The IBS features are strongly regulated by bidirectional gut-brain interactions and there is increasing evidence for the involvement of gut bacteria and/or their metabolites in these features, including visceral pain. Further, gut microbiota modulation by antibiotics or probiotics has been promising in IBS. Mechanistic data provided mainly by animal studies highlight that commensals or probiotics may exert a direct action through bacterial metabolites on sensitive nerve endings in the gut mucosa, or indirect pathways targeting the intestinal epithelial barrier, the mucosal and/or systemic immune activation, and subsequent neuronal sensitization and/or activation.     

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。