Gut microbiota role in irritable bowel syndrome: New therapeutic strategies

In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome(IBS). As a correlate, manipulation of gut microbiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial(Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful(Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required.     

Gut dysbiosis and irritable bowel syndrome: The potential role of probiotics

Objective

To discuss the role of gut dysbiosis in the development of irritable bowel syndrome (IBS) and the impact of probiotics as a potential therapeutic measure.

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.     

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.     

益生菌对肠易激综合征和炎症性肠病的作用

由于胃肠道微生物参与炎症性肠病（inflammatory bowel disease,IBD）的病理过程,而且最近研究表明微生物可能在肠易激综合征（irritable bowel syndrome,IBS）中扮演重要作用.本文重点关注益生菌在这两种疾病中的作用机制和疗效.胃肠道微生物的组成受多种因素调节,包括年龄、饮食和疾病状态.益生菌可能通过影响宿主的微生物菌群和提高黏膜的免疫调节作用发挥疗效.益生菌的口服耐受性较好.许多短期研究表明益生菌在IBS中有效,尽管只是在部分的特殊菌株和某些特定症状中有效.在IBD中,许多临床试验表明大量的益生菌在结肠袋炎和溃疡性结肠炎中有效,而对克罗恩病无明显疗效.显然,益生菌在IBS和IBD的治疗中能起到巨大的作用,但是,这些只是针对特殊的菌株.将来迫切需要进行高质量的临床研究和实验观察益菌对IBD和IBS的疗效.     

益生菌和肠易激综合征的关系

肠易激综合征(IBS)是最常见的功能性胃肠病之一,其发病机制目前还不明确。近年发现肠道微生物群可能参与了IBS的发生发展,细菌感染可以诱发感染后IBS;有一部分IBS患者存在小肠细菌过度生长(SIBO)或是菌群组成改变;口服肠道不吸收的抗生素能够减轻IBS的症状。因此有人提出用益生菌治疗IBS可能是一个合理的方法。此文就益生菌治疗IBS的相关研究作一综述。     

Lower Bifidobacteria counts in both duodenal mucosa-associated and fecal microbiota in irritable bowel syndrome patients

AIM： To determine the composition of both fecal and duodenal mucosa-associated microbiota in irritable bowel syndrome （IBS） patients and healthy subjects using molecular-based techniques.
METHODS： Fecal and duodenal mucosa brush samples were obtained from 41 IBS patients and 26 healthy subjects. Fecal samples were analyzed for the composition of the total microbiota using fluorescent in situ hybridization （FISH） and both fecal and duodenal brush samples were analyzed for the composition of bifidobacteria using real-time polymerase chain reaction.
RESULTS： The FISH analysis of fecal samples revealed a 2-fold decrease in the level of bifidobacteria （4.2 ± 1.3 vs 8.3 ± 1.9, P 〈 0.01） in IBS patients compared to healthy subjects, whereas no major differences in other bacterial groups were observed. At the species level, Bifidobacterium catenulatum levels were significantly lower （6 ± 0.6 vs 19 ± 2.5, P 〈 0.001） in the IBS patients in both fecal and duodenal brush samples than in healthy subjects.
CONCLUSION： Decreased bifidobacteria levels in both fecal and duodenal brush samples of IBS patients compared to healthy subjects indicate a role for microbiotic composition in IBS pathophysiology.     

Meta-analysis of probiotics for the treatment of irritable bowel syndrome

Irritable bowel syndrome （IBS） is a chronic condition affecting 3%-25% of the general population. As no curative treatment is available, therapy is aimed at reducing symptoms, often with little success. Because alteration of the normal intestinal microflora has been observed in IBS, probiotics （beneficial microbes taken to improve health） may be useful in reducing symptoms. This paper systematically reviews randomized, controlled, blinded bials of probiotics for the treatment of IBS and synthesizes data on efficacy across trials of adequate quality. Pubr4ed, Medline, Google Scholar, NIH registry of clinical trials, metaRegister, and the Cochrane Central Register of Controlled Trials were searched from 1982-2007. We also conducted secondary searches of reference lists, reviews, commentaries, relevant articles on associated diseases, books and meeting abstracts. Twenty trials with 23 probiotic treatment arms and a total of 1404 subjects met inclusion criteria. Probiotic use was associated with improvement in global IBS symptoms compared to placebo [pooled relative risk （RRpooled） 0.77, 95% confidence interval （95% CI） 0.62-0.94]. Probiotics were also associated with less abdominal pain compared to placebo [RRpooled = 0.78 （0.69-0.88）]. Too few studies reported data on other IBS symptoms or on specific probiotic strains to allow estimation of a pooled RR. While our analyses suggest that probiotic use may be associated with improvement in IBS symptoms compared to placebo, these results should be interpreted with caution, given the methodological limitations of contributing studies. Probiotics warrant further study as a potential therapy for IBS.     

肠易激综合征与肠道微生态的研究现状分析

肠易激综合征(IBS)发病机制复杂,目前没有统一的理论能解释IBS的发病,也没有单一的药物能缓解IBS的所有症状。此文就肠易激综合征与肠道微生态研究现状作一综述。     

鼠李糖乳杆菌治疗肠易激综合征机制新进展

肠易激综合征(irritable bowel syndrome,IBS)是临床上常见的功能性胃肠病,其会影响患者的生活质量.因此探寻IBS的有效治疗方法具有重要意义.益生菌可改善IBS患者的症状并提高其生活质量,其中备受关注的是鼠李糖乳杆菌(Lactobacillus rhamnosus GG,LGG).LGG是目前被...     

Probiotics and irritable bowel syndrome

Irritable bowel syndrome(IBS)is common gastrointestinal problems.It is characterized by abdominal pain or discomfort,and is associated with changes in stool frequency and/or consistency.The etiopathogenesis of IBS may be multifactorial,as is the pathophysiology,which is attributed to alterations in gastrointestinal motility,visceral hypersensitivity,intestinal microbiota,gut epithelium and immune function,dysfunction of the brain-gut axis or certain psychosocial factors.Current therapeutic strategies are often unsatisfactory.There is now increasing evidence linking alterations in the gastrointestinal microbiota and IBS.Probiotics are living organisms which,when ingested in certain numbers,exert health benefits beyond inherent basic nutrition.Probiotics have numerous positive effects in the gastrointestinal tract.Recently,many studies have suggested that probiotics are effective in the treatment of IBS.The mechanisms of probiotics in IBS are very complex.The purpose of this review is to summarize the evidence and mechanisms for the use of probiotics in the treatment of IBS.     

Recent advances in pharmacological treatment of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a highly prevalent functional disorder that reduces patients’ quality of life. It is a chronic disorder characterized by abdominal pain or discomfort associated with disordered defecation in the absence of identifiable structural or biochemical abnormalities. IBS imposes a significant economic burden to the healthcare system. Alteration in neurohumoral mechanisms and psychological factors, bacterial overgrowth, genetic factors, gut motility, visceral hypersensitivity, and immune system factors are currently believed to influence the pathogenesis of IBS. It is possible that there is an interaction of one or more of these etiologic factors leading to heterogeneous symptoms of IBS. IBS treatment is predicated upon the patient’s most bothersome symptoms. Despite the wide range of medications and the high prevalence of the disease, to date no completely effective remedy is available. This article reviews the literature from January 2008 to July 2013 on the subject of IBS peripherally acting pharmacological treatment. Drugs are categorized according to their administration for IBS-C, IBS-D or abdominal pain predominant IBS.     

Possible therapeutic role of Ig E blockade in irritable bowel syndrome

Omalizumab is a humanized monoclonal antibody that binds to the high-affinity type-I Ig E Fc receptors on mast cells(MCs) and basophils, inhibiting the Ig E immune pathway. Irritable bowel syndrome(IBS) is the most common functional gastrointestinal disorder, and dysregulation of the immune system likely contributes to its etiology and/or symptomatology. Colonic biopsies from patients with IBS demonstrate considerable increase in the number of degranulating MCs releasing histamine in proximity to nerves, and this event may underlie the common IBS symptom of abdominal pain. Pharmacologic control of MC activation and mediator release is a current area of active interest in the field of IBS research. Recently, we and Pearson et al described 2 cases of patients with IBS with diarrhea(IBS-D) showing positive clinical response to omalizumab. In both cases, the female patients had severe, long-lasting IBS-D and achieved an almost complete resolution of IBS symptoms. Both patients were also able to discontinue all IBS medications after commencing the anti-Ig E therapy. For both patients, the omalizumab treatment showed a relatively rapid onset of action, resembling the efficacy observed in and previously reported for patients with chronic spontaneous urticaria. In this Editorial, we discuss the possible biological mechanisms that may underlie the clinical efficacy of omalizumab in IBS. We suggest that there is a need for a well-designed prospective study to investigate the therapeutic effects of anti-Ig E in IBS.     

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.     

褪黑激素与肠易激综合征

肠易激综合征是一种原因不明的慢性肠功能紊乱性疾病，其发病机制尚不清楚。其治疗方法也在不断改进中，褪黑激素对肠易激综合征的治疗有着积极的作用。     

Overgrowth of the indigenous gut microbiome and irritable bowel syndrome

Culture-independent molecular techniques have demonstrated that the majority of the gut microbiota is uncultivable.Application of these molecular techniques to more accurately identify the indigenous gut microbiome has moved with great pace over recent years,leading to a substantial increase in understanding of gut microbial communities in both health and a number of disorders,including irritable bowel syndrome(IBS).Use of culture-independent molecular techniques already employed to characterise faecal and,to a lesser extent,colonic mucosal microbial populations in IBS,without reliance on insensitive,traditional microbiological culture techniques,has the potential to more accurately determine microbial composition in the small intestine of patients with this disorder,at least that occurring proximally and within reach of sampling.Current data concerning culture-based and culture-independent analyses of the small intestinal microbiome in IBS are considered here.     

肠易激综合征流行病学研究现状与进展

肠易激综合征(irritable bowel syndrome,IBS)是一种以慢性或者反复发作的腹痛伴排便习惯改变为特征的功能性肠病,并缺乏形态学和生化标志的异常。IBS是一种全球性疾病,人群患病率较高,其症状可反复发作,严重影响患者的生活质量,并占用了大量的医疗资源。IBS的病因和发病机制尚未明了,随着对IBS认识的不断深入和发展,国内外在不同时期,采用不同的标准和方法,对IBS的流行病学进行了较深入的研究,但不同国家和地区、不同人群的IBS患病率及其分布特征研究结果不尽相同,影响IBS的危险因素主要包括社会心理因素及遗传、感染、食物、药物因素等,现就近年来国内外IBS流行病学的研究情况作一综述。     

Emerging role of the gut microbiome in post-infectious irritable bowel syndrome: A literature review

Post-infectious irritable bowel syndrome (PI-IBS) is a particular type of IBS, with symptom onset after an acute episode of infectious gastroenteritis. Despite infectious disease resolution and clearance of the inciting pathogen agent, 10% of patients will develop PI-IBS. In susceptible individuals, the exposure to pathogenic organisms leads to a marked shift in the gut microbiota with prolonged changes in host-microbiota interactions. These changes can affect the gut-brain axis and the visceral sensitivity, disrupting the intestinal barrier, altering neuromuscular function, triggering persistent low inflammation, and sustaining the onset of IBS symptoms. There is no specific treatment strategy for PI-IBS. Different drug classes can be used to treat PI-IBS similar to patients with IBS in general, guided by their clinical symptoms. This review summarizes the current evidence for microbial dysbiosis in PI-IBS and analyzes the available data regarding the role of the microbiome in mediating the central and peripheral dysfunctions that lead to IBS symptoms. It also discusses the current state of evidence on therapies targeting the microbiome in the management of PI-IBS. The results of microbial modulation strategies used in relieving IBS symptomatology are encouraging. Several studies on PI-IBS animal models reported promising results. However, published data that describe the efficacy and safety of microbial targeted therapy in PI-IBS patients are scarce. Future research is required.     

State-of-the-art of irritable bowel syndrome and inflammatory bowel disease research in 2008

Irritable bowel syndrome （IBS） and inflammatory bowel disease （IBD） are two of the leading causes of chronic intestinal conditions in the world. This issue of World Journal of Gastroenterology （ WJG） presents a series of papers from world experts who discuss the current knowledge and opinions on these important conditions. Although great strides have been made in the diagnosis, treatment and pathology of IBS and IBD; much has yet to be explained. The etiologies and risk factors of these multifactorial conditions remain elusive. Specific diagnostic biomarkers need to be developed and safer treatments developed. The burden of IBS and IBD on the healthcare system is felt with repeated medical care visits and high costs. IBS and IBD patients can account for 30%-50% of office visits at gastroenterology services/clinics. Over one million people have IBD in the United States, with 30000 new cases being diagnosed every year. One-quarter million people in the UK are afflicted with IBD. The cost of medical care in the United States for IBD is estimated to be $1.8 billion/year.