Association of symptoms with gastrointestinal microbiota in irritable bowel syndrome

AIM:To investigate the correlations between selfreported symptoms of irritable bowel syndrome(IBS) and the gastrointestinal(GI) microbiota composition.METHODS:Fecal samples were collected from a total of 44 subjects diagnosed with IBS.Their symptoms were monitored with a validated inflammatory bowel disease questionnaire adjusted for IBS patients.Thirteen quantitative real-time polymerase chain reaction assays were applied to evaluate the GI microbiota composition.Eubacteria and GI bacterial genera(Bifidobacterium,Lactobacillus and Veillonella),groups(Clostridium coccoides/Eubacterium rectale,Desulfovibrio desulfuricans) and distinct bacterial phylotypes [closest 16S rDNA sequence resemblance to species Bifidobacterium catenulatum,Clostridium cocleatum,Collinsella aerofaciens(C.aerofaciens),Coprococcus eutactus(C.eutactus),Ruminococcus torques and Streptococcus bovis ] with a suspected association with IBS were quantified.Correlations between quantities or presence/absence data of selected bacterial groups or phylotypes and various IBSrelated symptoms were investigated.RESULTS:Associations were observed between subjects’ self-reported symptoms and the presence or quantities of certain GI bacteria.A Ruminococcus torques(R.torques)-like(94% similarity in 16S rRNA gene sequence) phylotype was associated with severity of bowel symptoms.Furthermore,among IBS subjects with R.torques 94% detected,the amounts of C.cocleatum 88%,C.aerofaciens-like and C.eutactus 97% phylotypes were significantly reduced.Interesting observations were also made concerning the effect of a subject’s weight on GI microbiota with regard to C.aerofaciens like phylotype,Bifidobacterium spp.and Lactobacillus spp.CONCLUSION:Bacteria seemingly affecting the symptom scores are unlikely to be the underlying cause or cure of IBS,but they may serve as biomarkers of the condition.     

肠道菌群检测方法学评价及其在肠易激综合征中的应用

正常情况下,肠道菌群组成的微生态系统对肠道功能和免疫防御等有着极其重要的作用,但肠道感染或抗生素的使用可能打破菌群平衡,从而表现出胃肠道症状,如肠易激综合征(IBS)。大量的IBS研究业已表明肠道菌群分析在肠道疾病的诊断和治疗中的重要价值。随着生物技术的发展,菌群分析的方法学也取得了较大进展。了解各种菌群分析的方法学特点并合理运用,对于保证肠道菌群检测的准确性及其临床应用具有重要意义。     

Effect of a calcium channel blocker and antispasmodic in diarrhoea-predominant irritable bowel syndrome

BACKGROUND: Irritable bowel syndrome (IBS) is a colonic function disorder. Both pinaverlum bromide (a selective calcium channel blocker) and mebeverine (an antispasmodic) are reported to be effective in the long-term (12-16 weeks) treatment of IBS patients. Their efficacy in the short-term treatment of IBS patients and colonic transit time is unclear. Furthermore, substance P and neuropeptide Y have either excitatory or inhibitory effects on colonic motility. Whether the efficacy of both drugs is mediated through these neuropeptides remains unknown. METHODS AND RESULTS: A clinical trial was conducted with 91 patients with diarrhoea-predominant IBS. After basal measurement of the total colonic transit time, IBS patients were randomized to receive either pinaverlum bromide (50 mg, t.i.d.) or mebeverine (100 mg, t.i.d.) for 2 weeks. The symptomatic scores regarding defaecation, total colonic transit time and serum levels of substance P and neuropeptide Y were measured before and after treatments. The daily defaecation frequency was markedly decreased after treatment (pinaverlum bromide, 2.9+/-1.2 vs 2.0+/-1.0, P< 0.05; mebeverine, 2.7+/-1.1 vs 2.1+/-1.0, P< 0.05). The stool consistency became well formed after both treatments (P< 0.05). Both drugs similarly improved the global well-being in these IBS patients (pinaverlum bromide vs mebeverine 73.4 vs 71.8%, P> 0.05). The total colonic transit time was significantly prolonged only after pinaverlum bromide treatment (21.4+/-15.5 vs 30.8+/-14.8 h, P< 0.01). Neither substance P nor neuropeptide Y serum level was significantly changed after either treatments. CONCLUSION: Pinaverlum bromide and mebeverine have similar therapeutic efficacies on diarrhoea-predominant IBS patients. Prolonged colonic transit time may be one of the factors responsible for the efficacy of pinaverlum bromide on the IBS patients. Substance P and neuropeptideY appear less important in the pathogenesis of diarrhoea-predominant IBS.     

Rifaximin is associated with modest,transient decreases in multiple taxa in the gut microbiota of patients with diarrhoea-predominant irritable bowel syndrome

Rifaximin, a non-systemic antibiotic, is efficacious for the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D). Given the emerging association between the gut microbiota and IBS, this study examined potential effects of rifaximin on the gastrointestinal microbial community in patients with IBS-D. TARGET 3 was a randomised, double-blind, placebo-controlled, phase 3 study. Patients with IBS-D initially received open-label rifaximin 550 mg 3 times daily (TID) for 2 weeks. Patients who responded to the initial treatment and then relapsed were randomised to receive 2 repeat courses of rifaximin 550 mg TID or placebo for 2 weeks, with each course separated by 10 weeks. Stool samples were collected at the beginning and end of open-label treatment, at the beginning and end of the first double-blind treatment, and at the end of the study. As a secondary analysis to the TARGET 3 trial, the composition and diversity of the gut microbiota were assessed, from a random subset of patients, using variable 4 hypervariable region 16S ribosomal RNA gene sequencing. Samples from 103 patients were included. After open-label rifaximin treatment for 2 weeks, 7 taxa (e.g. Peptostreptococcaceae, Verrucomicrobiaceae, Enterobacteriaceae) had significantly lower relative abundance at a 10% false discovery rate threshold. The effects of rifaximin were generally short-term, as there was little evidence of significantly different changes in taxa relative abundance at the end of the study (up to 46 weeks) versus baseline. The results suggest that rifaximin has a modest, largely transient effect across a broad range of stool microbes. Future research may determine whether the taxa affected by rifaximin are causally linked to IBS-D.

ClinicalTrials.gov identifier number: NCT01543178.     

Food-related gastrointestinal symptoms in the irritable bowel syndrome

BACKGROUND/AIMS: Postprandial symptoms are common in patients with irritable bowel syndrome (IBS). However, existing studies have come to different conclusions about the role of food in the pathophysiology of IBS. We explored the prevalence of subjective food-related gastrointestinal (GI) symptoms and its relationship to clinical characteristics and psychological factors in IBS. METHODS: 330 patients with IBS and 80 healthy volunteers completed a food questionnaire developed for this study. The subjects graded their subjective symptoms after 35 different foods and a food score was obtained by adding the item scores. The relationship between subjective food-related GI symptoms and referral status, IBS subgroup (predominant bowel pattern), sex, anxiety, depression and body mass index (BMI) was estimated. RESULTS: In 209 (63%) of the patients the GI symptoms were related to meals. Gas problems and abdominal pain were the most frequently reported symptoms. Foods rich in carbohydrates, as well as fatty food, coffee, alcohol and hot spices were most frequently reported to cause symptoms. The food score was higher in patients than in controls (p < 0.0001). In the IBS group higher scores were observed in patients with anxiety (p = 0.005), and females (p < 0.001), but the results were unrelated to IBS subgroup, referral status or BMI. The BMI did not differ between groups. CONCLUSION: A majority of IBS patients consider their symptoms to be related to meals. Especially foods rich in carbohydrates and fat cause problems. Nevertheless, the majority of IBS patients are normal or overweight. Female sex and anxiety predict a high degree of food-related symptoms in IBS.     

Comorbidity and use of health-care services among irritable bowel syndrome sufferers

OBJECTIVE: Patients suffering from irritable bowel syndrome (IBS) have more somatic and psychiatric comorbidity and use more health-care services for comorbid conditions than do other patients. Little is known about the frequency of comorbid symptoms among IBS sufferers in the general population and their influence on use of health-care facilities. The objective of this study was to compare the frequency of somatic and psychiatric symptoms between IBS sufferers and controls in the general population, and to study how comorbidity rates are distributed among consulters and non-consulters and how they predict the use of health care-services. MATERIAL AND METHODS: By means of a questionnaire sent to 5000 randomly selected adults IBS was identified according to the Rome II criteria. The questionnaire also covered upper GI symptoms, non-GI somatic symptoms, depression and anxiety. A logistic regression analysis with 26 variables was carried out to determine the independent predictors of health-care seeking for GI and non-GI complaints. RESULTS: The response rate was 73% and prevalence of IBS 5.1% (95% CI 4.4-5.8%). Dyspeptic symptoms, somatic extra-GI symptoms and psychiatric symptoms were reported by 45%, 69% and 51% of IBS sufferers, respectively, and 6%, 35% and 27%, of controls, respectively. Visiting a physician because of GI complaints was associated with disturbing abdominal symptoms, but not with depression or anxiety. Of the present GI conditions, only dyspeptic symptoms were associated with an increased consultation rate also for non-GI complaints. CONCLUSIONS: In the general population, both IBS consulters and non-consulters demonstrate high rates of comorbidity. Seeking health care for abdominal complaints is associated with abdominal symptoms rather than psychiatric comorbidity.     

Comorbidity and use of health-care services among irritable bowel syndrome sufferers

Objective. Patients suffering from irritable bowel syndrome (IBS) have more somatic and psychiatric comorbidity and use more health-care services for comorbid conditions than do other patients. Little is known about the frequency of comorbid symptoms among IBS sufferers in the general population and their influence on use of health-care facilities. The objective of this study was to compare the frequency of somatic and psychiatric symptoms between IBS sufferers and controls in the general population, and to study how comorbidity rates are distributed among consulters and non-consulters and how they predict the use of health care-services. Material and methods. By means of a questionnaire sent to 5000 randomly selected adults IBS was identified according to the Rome II criteria. The questionnaire also covered upper GI symptoms, non-GI somatic symptoms, depression and anxiety. A logistic regression analysis with 26 variables was carried out to determine the independent predictors of health-care seeking for GI and non-GI complaints. Results. The response rate was 73% and prevalence of IBS 5.1% (95% CI 4.4–5.8%). Dyspeptic symptoms, somatic extra-GI symptoms and psychiatric symptoms were reported by 45%, 69% and 51% of IBS sufferers, respectively, and 6%, 35% and 27%, of controls, respectively. Visiting a physician because of GI complaints was associated with disturbing abdominal symptoms, but not with depression or anxiety. Of the present GI conditions, only dyspeptic symptoms were associated with an increased consultation rate also for non-GI complaints. Conclusions. In the general population, both IBS consulters and non-consulters demonstrate high rates of comorbidity. Seeking health care for abdominal complaints is associated with abdominal symptoms rather than psychiatric comorbidity.     

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.     

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.     

Methodological issues in the study of intestinal microbiota in irritable bowel syndrome

Irritable bowel syndrome (IBS) is an intestinal functional disorder with the highest prevalence in the industrialized world. The intestinal microbiota (IM) plays a role in the pathogenesis of IBS and is not merely a consequence of this disorder. Previous research efforts have not revealed unequivocal microbiological signatures of IBS, and the experimental results are contradictory. The experimental methodologies adopted to investigate the complex intestinal ecosystem drastically impact the quality and significance of the results. Therefore, to consider the methodological aspects of the research on IM in IBS, we reviewed 29 relevant original research articles identified through a PubMed search using three combinations of keywords: “irritable bowel syndrome + microflora”, “irritable bowel syndrome + microbiota” and “irritable bowel syndrome + microbiome”. For each study, we reviewed the quality and significance of the scientific evidence obtained with respect to the experimental method adopted. The data obtained from each study were compared with all considered publications to identify potential inconsistencies and explain contradictory results. The analytical revision of the studies referenced in the present review has contributed to the identification of microbial groups whose relative abundance significantly alters IBS, suggesting that these microbial groups could be IM signatures for this syndrome. The identification of microbial biomarkers in the IM can be advantageous for the development of new diagnostic tools and novel therapeutic strategies for the treatment of different subtypes of IBS.     

Upper gastrointestinal and mental symptoms in the irritable bowel syndrome

Gastrointestinal and mental symptoms were assessed in 101 outpatients with the irritable bowel syndrome (IBS). A normal female population was used for comparison of mental symptoms. By definition all patients had abdominal pains and/or change of bowel habits (constipation or diarrhoea, or both) but no demonstrable organic disease. Upper gastrointestinal symptoms without peptic ulcer disease were reported by 87% of the patients. Mental symptoms were reported by almost all patients. Symptoms of anxiety, fatiguability, hostile feelings, sadness, and sleep disturbances were seen significantly more often among IBS women than in the controls. We conclude that patients with IBS frequently have upper gastrointestinal and mental symptoms that should be taken into account in the therapeutic management and evaluation of new modes of treatment.     

Rectal afferent hypersensitivity and compliance in irritable bowel syndrome: differences between diarrhoea-predominant and constipation-predominant subgroups

OBJECTIVES: To evaluate the differences in rectal compliance and sensory thresholds for the urge to defecate and discomfort between irritable bowel syndrome (IBS) subgroups and controls, and to correlate these parameters with rectal symptoms. METHODS: A total of 38 IBS patients [Rome II criteria; 19 diarrhoea-predominant IBS (D-IBS), 16 constipation-predominant IBS (C-IBS), three with alternating diarrhoea and constipation IBS (Alt-IBS)] and 10 controls were studied. A barostat was used to measure rectal compliance and sensory thresholds, in the 'unprepared' rectum. The thresholds for the urge to defecate and discomfort were determined using phasic rectal balloon distension in a double random staircase sequence. RESULTS: D-IBS had significantly lower rectal compliance and threshold for the urge to defecate compared with controls [4 ml/mmHg interquartile range (IQR) 3.99 versus 8.4 ml/mmHg IQR 5.69; P=0.001; 8 mmHg IQR 6 versus 20 mmHg IQR 4; P=0.003]. D-IBS also had significantly lower rectal compliance and threshold for the urge to defecate compared with the C-IBS group (5.8 ml/mmHg IQR 4.61; P=0.027; 16 mmHg IQR 12; P=0.003). The volume at the threshold for discomfort was significantly lower in D-IBS compared with controls (163 ml IQR 99.5 versus 212 ml IQR 147.25; P=0.016). The severity of abdominal pain and rectal symptoms showed a significantly negative correlation with rectal sensory thresholds. CONCLUSION: This study shows that the sensory threshold for the urge to defecate and rectal compliance is significantly lower in D-IBS compared with C-IBS and controls. The consequent inability to tolerate rectal faecal loading may account for the symptoms of the passage of frequent, small-volume stools in D-IBS patients.     

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.     

Medical costs in community subjects with irritable bowel syndrome

Costs of management of irritable bowel syndrome (IBS) are unknown. The direct medical charges in community subjects with IBS were estimated. An age- and sex-stratified random sample of residents of Olmsted County, Minnesota, ranging in age from 20 to 95 years, was mailed a valid self-report questionnaire. Subjects were categorized as having IBS, having some symptoms but inadequate criteria for IBS, and controls. All charges (in 1992 U.S. dollars) for health services rendered in the year before completing the survey were obtained (except outpatient medications). A total of 88% of subjects with IBS, 86% of subjects with some symptoms of IBS, and 83% of controls incurred direct medical charges during the study year. The odds of incurring charges were 1.6 times greater in subjects with IBS relative to those without symptoms (P < 0.01) adjusting for age, sex, education, marital status, and employment. Overall median charges incurred by subjects with IBS were $742 compared with $429 for controls and $614 for subjects with some symptoms. Among those subjects with nonzero charges, there were significant positive associations with age, higher education, and symptom groups (all P < 0.01) but not sex. The economic impact of IBS is significant. A better understanding of the determinants of these costs is needed so that cost-saving strategies can be implemented.     

睡眠质量与社区人群肠易激综合征相关性分析

目的 探讨上海市社区人群睡眠质量与肠易激综合征(IBS)患病率及两者之间的关系.方法 采用随机分层整群抽样方法,对上海市嘉定区江桥镇常住人群成年居民进行面访式问卷调查,回收有效调查问卷11 569份.采用罗马Ⅲ标准诊断IBS,阿森斯睡眠障碍量表进行自我评估,分析睡眠障碍与IBS之间的关系.结果 睡眠障碍在社区总人群、IBS患者及非IBS患者中发生率分别为21.00%、33.02%和18.74%.IBS组存在睡眠障碍比例高于非IBS组,两组间差异有统计学意义(P=0.004,OR=2.14,95%CI:1.92～2.39),即存在睡眠障碍的人群患IBS的危险性是无睡眠障碍人群的2.14倍.在IBS组,女性患者存在睡眠障碍的比例(37.24%)显著高于男性患者(28.41%),两组间差异有统计学意义(P=0.000,OR=1.50,95%CI:1.23～1.82),提示存在睡眠障碍的女性更易于患IBS.Logistic回归分析显示睡眠障碍是IBS的危险因素之一(OR=2.11,95%CI:1.89～2.36).结论 IBS患者常存在睡眠障碍,尤其是女性患者.