Pathogenesis Of Irritable Bowel Syndrome Research Articles

The Intestinal Microbiota and Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is the most prevalent and the best studied functional gastrointestinal disorder. The etiology and the pathogenesis of IBS are still not clear; however, recent studies have implicated a role for alterations in the intestinal microbiota (dysbiosis) in the pathophysiology of the disorder. Epidemiological observations have demonstrated that the development of IBS symptoms is often preceded by a disruption of the individual's normal intestinal microbiota, and microbiological studies have demonstrated compositional differences in the intestinal microbiota between patients with IBS patients and healthy controls. In addition, animal studies and a few recent human clinical studies have demonstrated that compositional changes in the intestinal microbiota in IBS are associated with relevant abnormal gastrointestinal and brain-gut axis functions that are often observed in patients with IBS. This article discusses points of interest from the current research on the microbiota-gut-brain interactions in IBS and highlights the relevance of the emerging data to our understanding of the disorder and the clinical implications for patients' care.

Tryptase and Protease-Activated Receptor 2 Expression Levels in Irritable Bowel Syndrome

Background/AimsPrevious studies have revealed that mast cells (MCs) may activate the protease-activated receptors and release of neuropeptides involved in the pathogenesis of irritable bowel syndrome (IBS). The levels of protease-activated receptor 2 (PAR-2) and tryptase can contribute to understanding the pathogenesis of IBS.MethodsColonoscopic biopsies were performed of 38 subjects (20 with IBS-diarrhea [IBS-D], eight with IBS-constipation [IBS-C], and 10 healthy volunteers). The mRNA and protein levels of tryptase and PAR-2 were assessed by real-time PCR and Western blot. The levels of vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) were measured by immunohistochemistry, and MCs were counted by toluidine blue staining.ResultsSignificant increases in the mRNA expression of tryptase (p<0.05, IBS-D, IBS-C vs control) and PAR-2 (p<0.05, IBS-D, IBS-C vs control) and in the tryptase protein level (p<0.05, IBS-D, IBS-C vs control) were detected in IBS. Elevations of MCs, CGRP, VIP and SP (p<0.05, IBS-D vs control) were observed for IBS-D only.ConclusionsTryptase levels may upregulate the function of PAR-2, resulting in the release of neuropeptide and they were correlated with clinical symptoms associated with IBS.

Breath Testing for Small Intestinal Bacterial Overgrowth in Irritable Bowel Syndrome: A Metaanalysis

Introduction: There is mounting evidence that the gastrointestinal microbiome and bacterial dysbiosis play an integral role in the pathogenesis of irritable bowel syndrome (IBS). While small bowel cultures remain the gold standard for diagnosis of small intestinal bacterial overgrowth (SIBO), breath testing remains the mainstay clinical tool to diagnose SIBO due to its non-invasive nature. We conducted a meta-analysis to determine the prevalence of SIBO in IBS subjects compared to healthy controls based on hydrogen breath testing. Methods: A literature search was performed using MEDLINE (1966 to May 2015) for case-control studies involving hydrogen breath testing in IBS patients compared to healthy controls based on an a priori definition of breath test positivity. Abstracts fulfilling inclusion criteria underwent full paper review. A second author verified the pooled data. We then conducted a meta-analysis based on a random effects model of the pooled data as well as data for each substrate to determine the odds ratio (OR) of breath test positivity among IBS subjects relative to healthy controls. Heterogeneity of the data was assessed by I2. Results: Nine studies were included in the final meta-analysis. The estimated prevalence of a positive breath test in IBS subjects was 36% (CI=16-55%) while in controls, the estimated prevalence was 15% (CI=8-22%).The odds ratio of a positive breath test was higher in IBS subjects versus healthy controls (OR=3.32, 95% confidence interval (CI) = 2.42-4.56). The studies were further analyzed based on geographical location (see figure 1) and stratified into North America (OR=1.83, 95% CI=1.09-3.08), Asia (OR=3.86, 95% CI=2.41-6.2), and Europe (OR=6.92, 95% CI=2.97-16.15). Significant heterogeneity was noted among the North American studies. Glucose was the most commonly used substrate in the nine studies (see figure 2) and had the highest odds of a positive breath test in IBS subjects versus healthy controls (OR=5.6, 95% CI=3.4-9.23). Studies that used glucose were more homogenous as compared with lactulose.Figure 1Figure 2Conclusion: In this meta-analysis of 1,641 patients in 9 case-control studies, we demonstrated that positive breath tests are more common among IBS patients in comparison to healthy controls. Our findings suggest that SIBO is more prevalent in an IBS population and are consistent with the bacterial overgrowth hypothesis for IBS.

The Aspects of Clinical Manifestation and Diagnostics of Irritable Bowel Syndrome in Infants

The work deals with the present conceptions concerning irritable bowel syndrome (IBS) in infants. IBS is a functional intestinal disorder when abdominal pain or discomfort are associated with defecation, or changes of the intestinal function and peculiarities of defecation. It is the only disease with various variants of the course connected with disorders of a regulating role of the central nervous system and vegetative dysfunctions resulting, first of all, in the development of motor disorders of the large intestine and is manifested by defecation disorders, changes of frequency and quality of stools, and is accompanied by abdominal pain. The main aspects of etiopathogenesis are: compromised heredity, increased sensitivity of the large intestine to extension, enzymatic insufficiency and imbalance of neuroendocrine mechanisms, disorders of the intestinal endocrine system, leading to the intensification of the intestinal motor function, secretion, activation of the kinin system, occurring of pain impulses, regulative disorders of psychic and sensory functions. The main factors playing their role in IBS pathogenesis are: disorders of a regulating role of the CNS and development of vegetative dysfunctions; motor disorders and disorders of intestinal biocoenosis, which can be treated as a target mechanism of IBS and/or as the consequence of the disease. Diagnostic criteria, approaches to interpret the findings of the study and the principles of IBS treatment in infants are estimated. The initial diagnosis of IBS is made on the basis of clinical signs, the final diagnosis – on the basis of a combined estimation of clinical and paraclinical examinations. Proctosigmoidoscopy is a compulsory examination which should be performed to make or exclude the diagnosis of IBS. The results of clinical-paraclinical examinations of infants with clinical signs of IBS, aged 3-4 years, are presented. Much more considerable level of albumin, A1-AT, calprotectin and sIgA were found in their evacuations as compared to the infants of the control group which is indicative of a local inflammation, increased permeability of the intestinal mucus and local allergic reaction, which can be a predictor to develop further atopic dermatitis. The changes mentioned above are accompanied by considerable alterations of intestinal microbiocoenosis, which is manifested by a decreased content of physiological microflora with prevailed colonies of opportunistic microorganisms. The diagnosis of IBS is the diagnosis of exclusion, it can be verified only in case other diseases are excluded (first of all, inflammatory intestinal diseases).The treatment of IBS requires a comprehensive therapy with the use of medicines of a combined regulation action, it should be accurately differentiated considering a clinical variant of its course and individual reaction of the patient, substantiated and well-considered administration of medicines, keeping to the essential period of treatment to prevent relapsed signs.

Food allergy in irritable bowel syndrome: The case of non-celiac wheat sensitivity.

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders, having a prevalence of 12%-30% in the general population. Most patients with IBS attribute their symptoms to adverse food reactions. We review the role of diet in the pathogenesis of IBS and the importance of dietary factors in the management of these patients. The MEDLINE electronic database (1966 to Jan 2015) was searched using the following keywords: "food", "diet", "food allergy", "food hypersensitivity", "food intolerance", "IBS", "epidemiology", "pathogenesis", "pathophysiology", "diagnosis", "treatment". We found 153 eligible papers; 80 were excluded because: not written in English, exclusive biochemical and experimental research, case reports, reviews, and research otherwise not relevant to our specific interest. We selected 73 papers: 43 original papers, 26 reviews and 4 letters to the editor. These papers focused on IBS pathogenesis, the association between IBS and atopy, and between IBS and food allergy, the relationship between IBS and non-celiac wheat sensitivity, the role of diet in IBS. Pending further scientific evidence, a cautious approach is advisable but the concept of food allergy should be included as a possible cause of IBS, and a dietary approach may have a place in the routine clinical management of IBS.

Microbiota-host interactions in irritable bowel syndrome: epithelial barrier, immune regulation and brain-gut interactions.

Irritable bowel syndrome (IBS) is a common, sometimes debilitating, gastrointestinal disorder worldwide. While altered gut motility and sensation, as well as aberrant brain perception of visceral events, are thought to contribute to the genesis of symptoms in IBS, a search for an underlying aetiology has, to date, proven unsuccessful. Recently, attention has been focused on the microbiota as a possible factor in the pathogenesis of IBS. Prompted by a number of clinical observations, such as the recognition of the de novo development of IBS following enteric infections, as well as descriptions of changes in colonic bacterial populations in IBS and supported by clinical responses to interventions, such as antibiotics and probiotics, that modify the microbiota, various approaches have been taken to investigating the microbiota-host response in IBS, as well as in animal models thereof. From such studies a considerable body of evidence has accumulated to indicate the activation or upregulation of both factors involved in bacterial engagement with the host as well host defence mechanisms against bacteria. Alterations in gut barrier function, occurring in response, or in parallel, to changes in the microbiota, have also been widely described and can be seen to play a pivotal role in generating and sustaining host immune responses both within and beyond the gut. In this manner a plausible hypothesis, based on an altered microbiota and/or an aberrant host response, for the pathogenesis, of at least some instances of IBS, can be generated.

Visceral hypersensitivity in irritable bowel syndrome: evidence for involvement of serotonin metabolism--a preliminary study.

Altered serotonergic (5-HT) metabolism and visceral perception have been associated with the pathogenesis of irritable bowel syndrome (IBS). Aim of this preliminary study was to assess the effect of the direct precursor of 5-HT, 5-hydroxytryptophan (5-HTP), on systemic 5-HT metabolites and visceral perception and to assess potential differential responses between IBS and controls. 15 IBS patients and 15 healthy volunteers participated in this randomized double-blind placebo controlled study. Visceroperception was measured by rectal barostat. The 100 mg 5-HTP or placebo was ingested orally. Serotonergic metabolites were assessed in platelet poor plasma. 5-HTP induces rectal allodynia in a significant number of healthy controls; IBS patients exhibit lowered pain thresholds in both placebo and 5-HTP conditions. 5-HTP induces rectal hyperalgesia in hypersensitive but not in non-hypersensitive IBS patients. Administration of 5-HTP significantly increased plasma 5-HTP levels (p < 0.001), did not affect 5-HT levels (p > 0.05), while levels of the main metabolite of 5-HT, 5-hydroxyindoleacetic acid, increased significantly (p < 0.05) in both groups. The magnitude of these changes observed in 5-HT metabolites was significantly greater in IBS patients. Oral administration of 5-HTP induced significant alterations in systemic 5-HT metabolites that were accompanied by increased visceroperception of pain in controls and hypersensitive IBS patients. Changes in 5-HT metabolism appear to be important factors involved in visceral hypersensitivity as the 5-HTP-induced pro-nociceptive response was observed in all hypersensitive IBS patients and to a lesser magnitude in a significant number of healthy controls but in none of the non-hypersensitive IBS patients.

肠道菌群生态失衡与肠易激综合征

The pathogenesis of irritable bowel syndrome (IBS) is still unclear. It may be associated with various factors. The patients suffered from IBS have intestinal flora ecological imbalance. There have been suggestions that intestinal flora ecological imbalance is associated with the pathogenesis of IBS since 1980s. Post-infective IBS (PI-IBS) has been proposed in recent years. It has obtained remarkable effect on restoring normal intestinal microbiota. So, intestinal microbiota shows a critical role in the pathogenesis of IBS. This paper reviews the relationship of intestinal flora ecological imbalance with IBS and the treatment progress of IBS.

Treatment of irritable bowel syndrome in China: a review.

Irritable bowel syndrome (IBS) is a common, chronic, functional gastrointestinal disorder with a high incidence rate in the general population, and it is common among the Chinese population. The pathophysiology, etiology and pathogenesis of IBS are poorly understood, with no evidence of inflammatory, anatomic, metabolic, or neoplastic factors to explain the symptoms. Treatment approaches are mainly focused on symptom management to maintain everyday functioning and to improve quality of life for patients with IBS. However, prescribed medications often result in significant side effects, and many IBS sufferers (particularly Chinese) do not improve. Instead of taking a variety of conventional medications, many have turned to taking traditional Chinese medicine or integrated Chinese and Western medicine for remedy. A number of clinical trials have shown that Chinese herbal, acupuncture or integrative therapies presented improved treatment outcomes and reduced side effects in IBS patients. The purpose of this review article is to examine the treatment approaches of IBS that have been published in recent years, especially in China, to assess the possible differences in treating IBS between China and other countries. This would provide some useful information of unique treatment approach in clinical practice for physicians in the management of IBS in China, thus offering more treatment options for IBS patients with potentially better treatment outcomes while reducing the medical cost burden.

Prevalence and Predictive Factors of Irritable Bowel Syndrome in a Community-dwelling Population in Japan

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by chronic, relapsing abdominal pain or discomfort and is associated with disturbed defecation. The pathogenesis of IBS is multifactorial. The aim of this study was to investigate the prevalence of IBS using the Rome III criteria and to assess the effects of mental and lifestyle factors on IBS in a community-dwelling population in Japan. The diagnosis of irritable bowel syndrome was based on the Japanese version of the Rome III Questionnaire. The questionnaire was administered to 993 volunteers who participated in the Iwaki Health Promotion Project 2013. Diet was assessed with a validated brief-type self-administered diet history questionnaire. Dietary patterns based on 52 predefined food groups [energy-adjusted food (g/d)] were extracted using a principal component analysis. The Center for Epidemiologic Studies Depression Scale with a cut-off point of 16 was used to assess the prevalence of depression. A total of 61 subjects (6.1%) were classified as having IBS. Three dietary patterns were identified: "Healthy", "Western" and "Alcohol and accompanying" dietary patterns. After adjusting for potential confounders, the "Alcohol and accompanying" dietary pattern and depression were related to the risk of IBS. We found that an "Alcohol and accompanying" dietary pattern and depression were related to the risk of IBS in a Japanese community population. However, we could not rule out the possibility of some selection bias. Further studies with longitudinal observations are therefore warranted.

Proinflammatory and anti-inflammatory cytokine profile in pediatric patients with irritable bowel syndrome

Background and objectivesThere is evidence that patients with irritable bowel syndrome (IBS) have a low degree of inflammation in the intestinal mucosa. The aim of the study was to evaluate theprofile of pro- and anti-inflammatory cytokinesin plasmain Mexican pediatric patients with IBS. Patients and methodsFifteen patients with IBS according to Rome III criteria for childhood and 15 healthy children, matched by age and sex, were included in the study. Plasma levels of tumoral necrosis factor alpha (TNF-α), interleukins 10 and 12 (IL-10, IL-12) and transforming growth factor beta (TGF-β) were quantified and compared between groups. ResultsPlasma levels of IL-10 were lower in patients with IBS (86.07+21.3 pg/mL vs. 118.71+58.62 pg/mL: P=.045) and IL-12 levels were higher in patients with IBS compared to the control group of healthy children (1,204.2±585.9 pg/mL vs. 655.04±557.80 pg/mL; P=.011). The IL-10/IL-12 index was lower in patients with IBS (0.097±0.07 vs. 0.295±0.336; P=.025). Plasma concentration of TGF-β was higher in patients with IBS (545.67±337.69 pg/mL vs. 208.48±142.21 pg/mL; P=.001). There was no difference in plasma levels of TNF-α between groups. ConclusionsThis study suggests that children with IBS have a state of altered immune regulation. This is consistent with the theory of low-grade inflammatory state in these patients. Further studies are needed to elucidate the role played by these cytokines, specifically TGF-β in the pathogenesis of IBS.

Proinflammatory and anti-inflammatory cytokine profile in pediatric patients with irritable bowel syndrome.

There is evidence that patients with irritable bowel syndrome (IBS) have a low degree of inflammation in the intestinal mucosa. The aim of the study was to evaluate the profile of pro- and anti-inflammatory cytokines in plasma in Mexican pediatric patients with IBS. Fifteen patients with IBS according to Rome III criteria for childhood and 15 healthy children, matched by age and sex, were included in the study. Plasma levels of tumoral necrosis factor alpha (TNF-α), interleukins 10 and 12 (IL-10, IL-12) and transforming growth factor beta (TGF-β) were quantified and compared between groups. Plasma levels of IL-10 were lower in patients with IBS (86.07+21.3 pg/mL vs. 118.71+58.62 pg/mL: P=.045) and IL-12 levels were higher in patients with IBS compared to the control group of healthy children (1,204.2±585.9 pg/mL vs. 655.04±557.80 pg/mL; P=.011). The IL-10/IL-12 index was lower in patients with IBS (0.097±0.07 vs. 0.295±0.336; P=.025). Plasma concentration of TGF-β was higher in patients with IBS (545.67±337.69 pg/mL vs. 208.48±142.21 pg/mL; P=.001). There was no difference in plasma levels of TNF-α between groups. This study suggests that children with IBS have a state of altered immune regulation. This is consistent with the theory of low-grade inflammatory state in these patients. Further studies are needed to elucidate the role played by these cytokines, specifically TGF-β in the pathogenesis of IBS.

Genetic polymorphism in pathogenesis of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a complex symptom-based disorder without established biomarkers or putative pathophysiology. IBS is a common functional gastrointestinal disorder which is defined as recurrent abdominal pain or discomfort that has at least two of the following symptoms for 3 d per month in the past 3 mo according to ROME III: relief by defecation, onset associated with a change in stool frequency or onset with change in appearance or form of stool. Recent discoveries revealed genetic polymorphisms in specific cytokines and neuropeptides may possibly influence the frequencies and severity of symptoms, as well as the therapeutic responses in treating IBS patients. This review gives new insights on how genetic determinations influence in clinical manifestations, treatment responses and potential biomarkers of IBS.

Dietary Renaissance in IBS: Has Food Replaced Medications as a Primary Treatment Strategy?

The medical community has only recently started to focus attention on the role of food in the pathogenesis of irritable bowel syndrome (IBS), though the association between food and gastrointestinal (GI) symptoms has been recognized by patients for decades. Health care providers receive little formal training in the dietary management of IBS and have traditionally viewed dietary interventions with skepticism. There is mounting evidence that links food to changes in motility, visceral sensation, microbiome, permeability, immune activation, and brain-gut interactions-all key elements in the pathogenesis of IBS. The role of specific dietary modification in the management of IBS has not been rigorously investigated until recently. There is now credible evidence suggesting that targeted dietary carbohydrate exclusion provides clinical benefits to IBS patients. There is emerging evidence to suggest that proteins such as gluten, as well as food chemicals, may play a role in IBS.

The Prevalence of Intestinal Parasites Is Not Greater Among Individuals With Irritable Bowel Syndrome: A Population-based Case-control Study

The parasites Dientamoeba fragilis and Blastocystis have been detected in feces from patients with irritable bowel syndrome (IBS), therefore these parasites may be involved in IBS pathogenesis. We proposed that a higher prevalence of the parasites in IBS subjects compared with asymptomatic controls would support such a mechanism. We aimed to determine the prevalence of these parasites in IBS subjects (cases) and controls and to identify risk factors associated with parasite carriage. We performed a population-based, case-control study of an adult population from an internet-based research institute in Denmark. In January 2010, subjects completed a questionnaire based on the Rome III criteria for IBS and answered questions on factors associated with parasite carriage. Respondents (n= 483) were asked to submit fecal samples for parasite testing; samples were analyzed from 124 cases and 204 controls. A greater proportion of controls than cases carried the parasites (50% vs 36%; P= .01). D fragilis was detected in a greater proportion of fecal samples from controls than cases (35% vs 23%; P= .03), as was Blastocystis (22% of controls vs 15% of cases; P= .09), and a greater percentage of controls carried more than 1 species of parasite (16% of controls vs 8% of cases; P= .05). D fragilis infection was associated with having children 5 to 18 years old in the household and Blastocystis infection was associated with high income (≥600,000 Danish Kroner/y, approximately $100,000 US dollars/y), no animals in the household, and drinking bottled water. D fragilis and Blastocystis were detected in a greater proportion of fecal samples from the asymptomatic background population in Denmark than from subjects with IBS symptoms. These findings indicate that these parasites are not likely to have a direct role in the pathogenesis of IBS. Longitudinal studies are required to understand their role in gastrointestinal health.

Effects of Clostridium butyricum combined with glutamine on the expression of intestinal tight junction protein in stress mouse model

Objective To investigate the mechanism of the permeability of intestinal mucosa in the pathogenesis of irritable bowel syndrome (IBS) and the interventional effects of Clostridium butyricum combined with glutamine.Methods According to random number method,fifty BALB/c mice were divided into control group,experimental control group,glutamine group,Clostridium butyricum group and combination group.IBS mice model was established by water-avoidance stress (WAS) experiment.The defecating time of mice and fecal water content were detected by dyed stool after mice gavaged with methylcellulose (1.5％).The pathological injury of intestine was assessed by hematoxylin and eosin staining.The visceral sensitivity was evaluated by colorectal distention test (CRD).The changes of the permeability of intestine was evaluated by detecting the changes of serum D-lactic acid (D-LA),level of diamine oxidase (DAO),expressions of intestinal epithelial cells (IEC) cell tight junction protein (TJ) (occludin-1,claudin-1,zonula occludens-1 (ZOL-1)) at protein level.The interventional effects of Clostridium butyricum combined with glutamine were evaluated.t test was performed for comparison between groups,and analysis of variance was used for comparison among multi-groups.Results Compared with the control group,the defecating time of experimental control group was significantly shorten ((100.40±14.80) min vs (75.88±12.20) min and water content of fecal significantly increased ((54.76±9.98)％ vs (74.95±7.15)％,t =3.692 and 4.023; P=0.002 and 0.002).The lowest threshold of visceral sensitivity significantly decreased ((40.87 ± 4.82) mmHg (1 mmHg=0.133 kPa) vs (27.80±3.18) mmHg; t=8.761,P＜0.01),while the mucosal pathological injury score significantly increased (0.50±0.15 vs2.60±0.97; t＝6.034,P＜0.01).The level of D-LA ((1 476±246.8) ng/L vs (913.6±90.1) ng/L)) and DAO ((3 391.0±256.9) vs (5 096.0±725.2) ng/L) significantly increased (t=40.920 and 29.810; both P＜0.05),and the expression of tight junction protein ZOL-1 (0.165±0.005 vs0.119±0.003),occludin-1 (0.104±0.016 vs 0.022±0.006) significantly decreased (t=19.830 and 19.830; both P＜0.01).Compared with the experimental control group,after intragastric intervention the defecating time of glutamine group,Clostridium butyricum group and combination group increased ((90.50±3.78),(97.56±8.79) and (99.89±11.90) min and water content of fecal decreased ((69.33±6.71)％,(58.07±8.97)％ and (56.74±8.12)％) and the differences were statistically significant (F=10.020 and 8.740; both P＜0.01).The results of Clostridium butyricum group and combination group were good (F=2.481 and 4.874; both P＜0.05).And the lowest threshold of visceral sensitivity significantly increased ((31.80±2.69),(36.04±5.06) and (38.93±3.30) mmHg; F=2.420,P＜0.05),the result of combination group was the best (F=3.550,P＜0.01).Jejunal mucosal injury was significantly reduced (2.00 ± 0.94,1.30 ± 0.68 and 1.30±0.48; F＝11.350,P＜0.01).After intragastric intervention,serum levels of D-LA ((1 370.0± 78.9),(1 066.0±155.5) and (1 039.0±129.0) ng/L) and DAO ((4 808.0±477.4),(3 713.0± 595.0) and (3 725.0±615.9) ng/L) of glutamine group,Clostridium butyricum group and combination group significantly decreased (F＝37.480 and 27.670; both P＜0.01).The level of ZOL-1(0.126± 0.014,0.125±0.006,0.138±0.004) and occludin 1 (0.037±0.013,0.073±0.028,0.078±0.027) of glutamine group,Clostridium butyricum group and combination group significantly increased,and the differences were statistically significant (F=5.867 and 10.630; both P＜0.05).The change of ZOL-1 of combination group was more than that of Clostridium butyricum group (t =5.457,P ＜ 0.05).Conclusions WAS experiment can induce visceral hypersensitivity,increase the permeability of intestine and reduce the function of intestinal epithelial barrier.Clostridium butyricum and glutamine are effective in the recovery of visceral hypersensitivity and the permeability of mucosal epithelia cells. Key words: Stress; Tight junctions protein; Intestinal permeability; Clostridium butyricum; Glutamine

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.

Irritable bowel syndrome and food interaction.

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders in Western countries. Despite the high prevalence of this disorders, the therapeutic management of these patients is often unsatisfactory. A number of factors have been suggested to be involved in the pathogenesis of IBS, including impaired motility and sensitivity, increased permeability, changes in the gut microbiome and alterations in the brain-gut axis. Also food seems to play a critical role: the most of IBS patients report the onset or the exacerbation of their symptoms after the meals. Recently, an increasing attention has been paid to the role of food in IBS. In this review we summarize the most recent evidences about the role of diet on IBS symptoms. A diet restricted in fermentable, poorly absorbed carbohydrates and sugar alcohols has beneficial effects on IBS symptoms. More studies are needed to improve our knowledge about the relationship between food and IBS. However, in the foreseeable future, dietary strategies will represent one of the key tools in the therapeutic management of patients with IBS.

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.

Tryptophan: ‘essential’ for the pathogenesis of irritable bowel syndrome?

IntroductionTryptophan is an ‘essential’ amino acid: humanscannot make it themselves, but must obtain it inthe form of food. In addition to being a buildingblock in the biosynthesis of proteins, this aromaticsubstance can be converted into a number of meta-bolites of great clinical importance. The best known isthe enzymatic conversion to serotonin. However, inrecent years, attention has increasingly focused on themedical significance of the enzymatic oxidation oftryptophan to form indole compounds collectivelyknown as kynurenines. Both excessive kynurenineproduction and an accompanying deficiency of thesubstrate, tryptophan, may be the cause of a numberof pathological conditions. In addition, the oxidationitself may affect the body’s redox balance. In thisarticle, we hypothesize that tryptophan is ‘essential’inthepathogenesisofirritablebowelsyndrome (IBS).Indolamine dioxygenaseIndolamine dioxygenase (IDO) is the key enzymeinvolved in the conversion of tryptophan in the intes-tine. The enzyme catalyses oxidation of tryptophan tokynurenine in a reaction that produces peroxide andgives rise to highly reactive and potentially harmfuloxygen and hydroxyl radicals. The IDO reaction maytherefore contribute to what is generally calledoxidative stress [1,2]. Oxygen and hydroxyl radicalsformed as a result of the IDO reaction will acceleratethe oxidation of nitrogen monoxide (NO) to nitrite(NO