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.     

IBS-associated phylogenetic unbalances of the intestinal microbiota are not reverted by probiotic supplementation

IBS is a prevalent functional gastrointestinal disorder, in which the microbiota has been demonstrated to play a role. An increasing number of studies have suggested how probiotics may alleviate IBS symptoms and several mechanisms of action have been proposed.

In the present study we characterized the intestinal microbiota of 19 subjects suffering from diagnosed IBS using a fully validated High Taxonomic Fingerprint Microbiota Array (HTF-Microbi.Array). We demonstrated that the IBS microbiota is different from that of healthy individuals due to an unbalance in a number of commensal species, with an increase in relative abundance of lactobacilli, B. cereus and B. clausii, bifidobacteria, Clostridium cluster IX and E. rectale, and a decrease in abundance of Bacteroides/Prevotella group and Veillonella genus. Additionally, we demonstrated that some bacterial groups of the human intestinal microbiota, recently defined as pathobionts, are increased in concentration in the IBS microbiota.

Furthermore, we aimed at investigating if the daily administration of a novel probiotic yogurt containing B. animalis subsp lactis Bb12 and K. marxianus B0399, recently demonstrated to have beneficial effects in the management of IBS symptoms, could impact on the biostructure of IBS microbiota, modulating its composition to counteract putative dysbiosis found in IBS subjects. Notably, we demonstrated that the beneficial effects associated to the probiotic preparation are not related to significant modifications in the composition of the human intestinal microbiota.     

IBS-associated phylogenetic unbalances of the intestinal microbiota are not reverted by probiotic supplementation

IBS is a prevalent functional gastrointestinal disorder, in which the microbiota has been demonstrated to play a role. An increasing number of studies have suggested how probiotics may alleviate IBS symptoms and several mechanisms of action have been proposed. In the present study we characterized the intestinal microbiota of 19 subjects suffering from diagnosed IBS using a fully validated High Taxonomic Fingerprint Microbiota Array (HTF-Microbi.Array). We demonstrated that the IBS microbiota is different from that of healthy individuals due to an unbalance in a number of commensal species, with an increase in relative abundance of lactobacilli, B. cereus and B. clausii, bifidobacteria, Clostridium cluster IX and E. rectale, and a decrease in abundance of Bacteroides/Prevotella group and Veillonella genus. Additionally, we demonstrated that some bacterial groups of the human intestinal microbiota, recently defined as pathobionts, are increased in concentration in the IBS microbiota. Furthermore, we aimed at investigating if the daily administration of a novel probiotic yogurt containing B. animalis subsp lactis Bb12 and K. marxianus B0399, recently demonstrated to have beneficial effects in the management of IBS symptoms, could impact on the biostructure of IBS microbiota, modulating its composition to counteract putative dysbiosis found in IBS subjects. Notably, we demonstrated that the beneficial effects associated to the probiotic preparation are not related to significant modifications in the composition of the human intestinal microbiota.     

Upper gastrointestinal microbiota and digestive diseases

Metagenomics which combines the power of genomics,bioinformatics,and systems biology,provide new access to the microbial world.Metagenomics permit the genetic analysis of complex microbial populations without requiring prior cultivation.Through the conceptual innovations in metagenomics and the improvements in DNA high-throughput sequencing and bioinformatics analysis technology,gastrointestinal microbiology has entered the metagenomics era and become a hot topic worldwide.Human microbiome research is underway,however,most studies in this area have focused on the composition and function of the intestinal microbiota and the relationship between intestinal microbiota and metabolic diseases(obesity,diabetes,metabolic syndrome,etc.) and intestinal disorders [inflammatory bowel disease,colorectal cancer,irritable bowel syndrome(IBS),etc.].Few investigations on microbiota have been conducted within the upper gastrointestinal tract(esophagus,stomach and duodenum).The upper gastrointestinal microbiota is essential for several gastrointestinal illnesses,including esophagitis,Barrett’s esophagus,and esophageal carcinoma,gastritis and gastric cancer,small intestinal bacterial overgrowth,IBS and celiac disease.However,the constitution and diversity of the microbiota in different sections of the upper gastrointestinal tract under health and various disease states,as well as the function of microbiota in the pathogenesis of various digestive diseases are still undefined.The current article provides an overview of the recent findings regarding the relationship between upper gastrointestinal microbiota and gastrointestinal diseases;and discusses the study limitations and future directions of upper gastrointestinal microbiota research.     

Intestinal microbiota in pathophysiology and management of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a functional bowel disorder without any structural or metabolic abnormalities that sufficiently explain the symptoms, which include abdominal pain and discomfort, and bowel habit changes such as diarrhea and constipation. Its pathogenesis is multifactorial: visceral hypersensitivity, dysmotility, psychosocial factors, genetic or environmental factors, dysregulation of the brain-gut axis, and altered intestinal microbiota have all been proposed as possible causes. The human intestinal microbiota are composed of more than 1000 different bacterial species and 10¹⁴ cells, and are essential for the development, function, and homeostasis of the intestine, and for individual health. The putative mechanisms that explain the role of microbiota in the development of IBS include altered composition or metabolic activity of the microbiota, mucosal immune activation and inflammation, increased intestinal permeability and impaired mucosal barrier function, sensory-motor disturbances provoked by the microbiota, and a disturbed gut-microbiota-brain axis. Therefore, modulation of the intestinal microbiota through dietary changes, and use of antibiotics, probiotics, and anti-inflammatory agents has been suggested as strategies for managing IBS symptoms. This review summarizes and discusses the accumulating evidence that intestinal microbiota play a role in the pathophysiology and management of IBS.     

Irritable bowel syndrome: the role of the intestinal microbiota, pathogenesis and therapeutic targets

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that predominantly affects women and accounts for up to 40% of the gastroenterology unit outpatient visits. The pathophysiology is complex and multifactorial. In the present review we will focus on the role of intestinal dysbiosis in its pathogenesis and treatment. Post-infectious IBS (PI-IBS) can put light on the mechanisms underlying IBS. Modified commensal gut flora may lead to mucosal inflammation. Several changes such as an increase in mucosal cellularity (enterochromaffin cells, lamina propria T lymphocytes and mast cells), modified pro-inflammatory/anti-inflammatory cytokine balance and disordered neurotransmission have been observed. The normal microbiota is an essential factor in health. A modification of the flora, such as small intestinal bacterial overgrowth (SIBO) is thought to play a pathogenic role in IBS. Changes in the composition of the luminal and mucosal colonic flora have been linked to IBS. It is not clear however, whether these changes are a cause or a consequence of the syndrome. The comprehension of the interaction between the dysbiotic microbiota and the host will probably lead to the development of focused therapies. Based on these assumptions, treatments modulating the microbiota have been investigated. On the one hand several probiotics have shown a reduction in IBS symptoms by an immunomodulatory and analgesic effects. On the other hand antibiotic treatment has proven efficacy in treating IBS with or without associated SIBO. Due to its complex pathophysiology, treating IBS nowadays implies multiple approaches, one of which may be modulation of the intestinal flora.     

Pathogenic factors involved in the development of irritable bowel syndrome: focus on a microbial role

Irritable bowel syndrome (IBS) is a symptom complex characterized by recurrent abdominal pain or discomfort, and accompanied by abnormal bowel habits, in the absence of any discernible organic abnormality. Its origin remains unclear, partly because multiple pathophysiologic mechanisms are likely to be involved. A significant proportion of patients develop IBS symptoms after an episode of gastrointestinal infection. In addition to gastrointestinal pathogens, recent evidence suggests that patients with IBS have abnormal composition and higher temporal instability of their intestinal microbiota. Because the intestinal microbiota is an important determinant of normal gut function and immunity, this instability may constitute an additional mechanism that leads to symptom generation and IBS. More importantly, a role for altered microbiota composition in IBS raises the possibility of therapeutic interventions through selective antibiotic or probiotic administration. The new concept of functional bowel diseases incorporates the bidirectional communication between the gut and the central nervous system (gut-brain axis), which may explain the multiple facets of IBS by linking emotional and cognitive centers of the brain with peripheral functioning of the gastrointestinal tract and vice versa.     

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.     

The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a significant gastrointestinal disorder with unknown etiology. The symptoms can greatly weaken patients' quality of life and account for notable economical costs for society. Contribution of the gastrointestinal microbiota in IBS has been suggested. Our objective was to characterize putative differences in gastrointestinal microbiota between patients with IBS and control subjects. These differences could potentially have a causal relationship with the syndrome. METHODS: Microbial genomes from fecal samples of 24 patients with IBS and 23 controls were collected, pooled in a groupwise manner, and fractionated according to their guanine cytosine content. Selected fractions were analyzed by extensive high-throughput 16S ribosomal RNA gene cloning and sequencing of 3753 clones. Some of the revealed phylogenetic differences were further confirmed by quantitative polymerase chain reaction assays on individual samples. RESULTS: The coverage of the clone libraries of IBS subtypes and control subjects differed significantly (P < .0253). The samples were also distinguishable by the Bayesian analysis of bacterial population structure. Moreover, significant (P < .05) differences between the clone libraries were found in several bacterial genera, which could be verified by quantitative polymerase chain reaction assays of phylotypes belonging to the genera Coprococcus, Collinsella, and Coprobacillus. CONCLUSIONS: The study showed that fecal microbiota is significantly altered in IBS. Further studies on molecular mechanisms underlying these alterations are needed to elucidate the exact role of intestinal bacteria in IBS.     

Recent developments in the pathophysiology of irritable bowel syndrome

Irritable bowel syndrome(IBS) is a common gastrointestinal disorder, the pathophysiology of which is not completely known, although it has been shown that genetic/social learning factors, diet, intestinal microbiota, intestinal low-grade inflammation, and abnormal gastrointestinal endocrine cells play a major role. Studies of familial aggregation and on twins have confirmed the heritability of IBS. However, the proposed IBS risk genes are thus far nonvalidated hits rather than true predisposing factors. There is no convincing evidence that IBS patients suffer from food allergy/intolerance, with the effect exerted by diet seemingly caused by intake of poorly absorbed carbohydrates and fiber. Obesity is a possible comorbidity of IBS. Differences in the microbiota between IBS patients and healthy controls have been reported, but the association between IBS symptoms and specific bacterial species is uncertain. Low-grade inflammation appears to play a role in the pathophysiology of a major subset of IBS, namely postinfectious IBS. The density of intestinal endocrine cells is reduced in patients with IBS, possibly as a result of genetic factors, diet, intestinal microbiota, and low-grade inflammation interfering with the regulatory signals controlling the intestinal stem-cell clonogenic and differentiation activities. Furthermore, there is speculation that this decreased number of endocrine cells is responsible for the visceral hypersensitivity, disturbed gastrointestinal motility, and abnormal gut secretion seen in IBS patients.     

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.     

Sex hormones in the modulation of irritable bowel syndrome

Compelling evidence indicates sex and gender differences in epidemiology,symptomatology,pathophysiology,and treatment outcome in irritable bowel syndrome(IBS).Based on the female predominance as well as the correlation between IBS symptoms and hormonal status,several models have been proposed to examine the role of sex hormones in gastrointestinal(GI)function including differences in GI symptoms expression in distinct phases of the menstrual cycle,in pre-and post-menopausal women,during pregnancy,hormonal treatment or after oophorectomy.Sex hormones may influence peripheral and central regulatory mechanisms of the brain-gut axis involved in the pathophysiology of IBS contributing to the alterations in visceral sensitivity,motility,intestinal barrier function,and immune activation of intestinal mucosa.Sex differences in stress response of the hypothalamic-pituitary-adrenal axis and autonomic nervous system,neuroimmune interac-tions triggered by stress,as well as estrogen interactions with serotonin and corticotropin-releasing factor signaling systems are being increasingly recognized.A concept of"microgenderome"related to the potential role of sex hormone modulation of the gut microbiota is also emerging.Significant differences between IBS female and male patients regarding symptomatology and comorbidity with other chronic pain syndromes and psychiatric disorders,together with differences in efficacy of serotonergic medications in IBS patients confirm the necessity for more sex-tailored therapeutic approach in this disorder.     

肠道菌群失调与肠易激综合征的研究进展

肠易激综合征（IBS）的发病机制复杂,可能与内脏感觉过敏、胃肠道动力异常、肠道菌群失调、小肠细菌过度生长、肠道感染、食物不耐受、免疫异常、社会心理因素以及脑一肠轴异常等有关。研究显示,肠道菌群失调可能与IBS症状的产生和持续有关。本文就肠道菌群失调与IBS的研究进展作一综述。     

小肠细菌过度生长在肠易激综合征中的研究进展

肠易激综合征(IBS)是一种常见的功能性胃肠病,其发病机制复杂。目前认为IBS与胃肠动力障碍、内脏高敏感、肠道感染、脑-肠轴功能紊乱、免疫活化等因素有关。最新研究表明小肠细菌过度生长(SIBO)在IBS的发病中亦起重要作用。本文就SIBO在IBS中的研究进展,包括病理生理机制、诊断、治疗等作一综述。     

Bile acids and FXR in functional gastrointestinal disorders

Functional gastrointestinal disorders (FGIDs), such as irritable bowel syndrome (IBS) and chronic constipation (CC), are commonly diagnosed conditions in clinical practice which create a substantial global burden. Since the farnesoid X receptor (FXR) and bile acids (BAs) are responsible for maintaining homeostasis in the GI tract, any disturbances in the expression of FXR or the composition of BAs may contribute to the development of the GI symptoms. Alterations in the mechanism of action of FXR directly affect the BAs pool and account for increased intestinal permeability and changes in abundance and diversity of gut microbiota leading to intestinal dysmotility.Current review focuses on the correlation between the FXR, BAs and the composition of gut microbiota and its influence on the occurrence of GI symptoms in FGIDs.     

Gastrointestinal microbiota in irritable bowel syndrome: their role in its pathogenesis and treatment

Irritable bowel syndrome (IBS) is a chronic disorder characterized by abdominal pain, change in bowel habit, and bloating. It has traditionally been viewed as a disorder of visceral hypersensitivity heavily influenced by stress, and therefore therapeutic strategies to date have largely reflected this. However, more recently, there is good evidence for a role of the gastrointestinal (GI) microbiota in its pathogenesis. Changes in fecal microbiota, the use of probiotics, the phenomenon of postinfectious IBS, and the recognition of an upregulated host immune system response suggest that an interaction between the host and GI microbiota may be important in the pathogenesis of IBS. This article explores the role of the GI microbiota in IBS and how their modification might lead to therapeutic benefit.     

感染后肠易激综合征研究现状

肠易激综合征（IBS）是最常见的功能性胃肠病之一,已有研究证据表明其可能是多种因素共同作用的结果,包括遗传和环境因素、胃肠动力改变、内脏高敏感、肠道感染和炎症、慢性应激、肠道细菌过度生长和脑-肠轴功能紊乱等。部分患者在急性肠道感染恢复后仍存在腹痛、腹部不适、腹泻等症状,即感染后肠易激综合征（PI-IBS）,是近年功能性胃肠病的研究热点。本文就PI-IBS的定义、流行病学、发病机制、动物模型、临床特征、诊断和治疗等研究现状作一概述。     

Bacterial proteases in IBD and IBS

Proteases play a decisive role in health and disease. They fulfil diverse functions and have been associated with the pathology of gastrointestinal disorders such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). The current knowledge focuses on host-derived proteases including matrix metalloproteinases, various serine proteases and cathepsins. The possible contribution of bacterial proteases has been largely ignored in the pathogenesis of IBD and IBS, although there is increasing evidence, especially demonstrated for proteases from pathogenic bacteria. The underlying mechanisms extend to proteases from commensal bacteria which may be relevant for disease susceptibility. The intestinal microbiota and its proteolytic capacity exhibit the potential to contribute to the pathogenesis of IBD and IBS. This review highlights the relevance of host- and bacteria-derived proteases and their signalling mechanisms.     

Gut bless you: The microbiota-gut-brain axis in irritable bowel syndrome

Irritable bowel syndrome(IBS)is a common clinical label for medically unexplained gastrointestinal symptoms,recently described as a disturbance of the microbiota-gut-brain axis.Despite decades of research,the pathophysiology of this highly heterogeneous disorder remains elusive.However,a dramatic change in the understanding of the underlying pathophysiological mechanisms surfaced when the importance of gut microbiota protruded the scientific picture.Are we getting any closer to understanding IBS’etiology,or are we drowning in unspecific,conflicting data because we possess limited tools to unravel the cluster of secrets our gut microbiota is concealing?In this comprehensive review we are discussing some of the major important features of IBS and their interaction with gut microbiota,clinical microbiota-altering treatment such as the low FODMAP diet and fecal microbiota transplantation,neuroimaging and methods in microbiota analyses,and current and future challenges with big data analysis in IBS.