Effects of a Bacillus subtilis HU58 and Heyndrickxia faecalis SC208 spore-forming probiotic formula on gastrointestinal health: results of arandomised, double-blind, placebo-controlled pilot study.

A prospective assessment of bowel habit in irritable bowel syndrome in women: Defining an alternator

Understanding the Multidimensional Nature of Illness Severity as Measured by Patient-Reported Outcome Measures in Irritable Bowel Syndrome

Functional Bowel Disorders

American Gastroenterological Association Institute Guideline on the Pharmacological Management of Irritable Bowel Syndrome

Introduction: A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) has been shown to reduce symptoms among adult patients and children with irritable bowel syndrome. There are no studies investigating the effectiveness of the low FODMAP diet in pediatric patients with functional abdominal pain (FAP). Objective: The study aimed to evaluate the effectiveness of the low FODMAP diet in reducing gastrointestinal symptoms in children with FAP in comparison to the control diet based on the National Institute for Health and Care Excellence (NICE) guidelines. Methods: Twenty-seven children with diagnosed FAP were randomized to 2 groups. Each group received an intervention: the low FODMAP diet or the diet based on NICE. All food was prepared and delivered by a catering company. Data regarding gastrointestinal symptoms were recorded by participants during the 2-week baseline assessment and 4-week dietary intervention. The frequencies of abdominal pain and stools were reported as a number of events per day. The severity of abdominal pain was assessed using the Wong-Baker FACES Pain Rating Scale. The assessment of stool consistency was based on the Bristol Stool Form Scale. Results: The tendency toward the improvement in abdominal symptoms was noted in the low FODMAP group but without statistical significance. No significant differences in stool consistency were observed in this group. The NICE group experienced significant reduction in abdominal pain intensity and frequency (p < 0.01) and improvement in stool consistency (93% reporting normal stool, p < 0.05). Conclusions: The results of this pilot study suggest that the low FODMAP diet is not effective in the reduction of symptoms in children with FAP.

Purpose: Patients with irritable bowel syndrome (IBS) frequently identify worsening of symptoms after meals, citing certain foods including increased carbohydrates as triggers of their symptoms, particularly among those with diarrhea-predominant IBS (IBS-D). Patients with IBS-D anecdotally report improvement in symptoms after initiating a very low carbohydrate diet (VLCD), but no study has investigated the effect of a VLCD in IBS-D. The purpose of this study is to determine the effect of a VLCD in overweight and obese individuals with IBS-D. Methods: Eligible participants were those with a body mass index > 25 kg/m2 who met Rome II criteria for IBS-D and had at least moderately severe IBS, as defined by a score of > 36 on the Functional Bowel Disorder Severity Index. Participants were provided a standard diet for 2 weeks, followed by a VLCD (20 grams of carbohydrates/day) for 4 weeks. The primary outcome was adequate relief (AR), as assessed by a weekly one-item questionnaire during the 4 weeks of the VLCD. A responder was a participant who reported AR of all GI symptoms in at least 2 of the 4 weeks during the VLCD. Using daily diary cards for all 6 weeks, participants recorded daily stool frequency, stool consistency using the Bristol Stool Scale (BSS) that ranges from 1 (hard/lumpy) to 7 (watery), and abdominal pain using a visual analog scale (VAS, scale of 0–100). Participants also recorded AR daily during the VLCD. The IBS Quality of Life (IBS-QOL) and Sickness Impact Profile (SIP) questionnaires were administered before and after the 4-week VLCD trial. Results: A total of 17 individuals were enrolled: 1 dropped out during Week 1 of the study (intolerance of standard diet), 3 dropped out during Week 3 of the study (2 due to intolerance of the VLCD and 1 due to emotional symptoms), and 13 completed all 6 weeks. During the VLCD, all 13 participants met the responder definition and also had AR at week 4 of the VLCD. Furthermore, 10/13 participants reported AR for all 4 weeks of the VLCD, and AR for at least 90% of the days during the VLCD. Stool frequency decreased from a mean (±SD) of 2.6 ± 0.8/day to 1.4 ± 0.6/day (P < 0.001) and stool consistency improved on BSS from 5.3 ± 0.7 to 3.8 ± 1.2 (P < 0.001). Pain scores (VAS) decreased from 26 ± 18 to 10 ± 10 (P= 0.007). Both the IBS-QOL (71 ± 22 to 81 ± 13; P= 0.02) and the SIP (5.5 ± 6.4 to 2.3 ± 3.6; P= 0.001) showed clinically meaningful improvement. Finally, although participants lost an average of 3.1 ± 1.7 kg (P < 0.0001), clinical improvement was independent of weight loss. Conclusion: In this open label study, initiation of a VLCD in overweight and obese individuals with IBS-D for 4 weeks provides adequate relief, decreases abdominal pain, improves stool frequency and consistency, and improves quality of life.

Irritable bowel syndrome (IBS) and chronic idiopathic constipation ((CIC) also referred to as functional constipation) are two of the most common functional gastrointestinal disorders worldwide. IBS is a global problem, with anywhere from 5 to 15% of the general population experiencing symptoms that would satisfy a definition of IBS (1,2). In a systematic review on the global prevalence of IBS, Lovell and Ford (1) documented a pooled prevalence of 11% with all regions of the world suffering from this disorder at similar rates. Given its prevalence, the frequency of symptoms, and their associated debility for many patients and the fact that IBS typically occurs in younger adulthood, an important period for furthering education, embarking on careers, and/or raising families, the socioeconomic impact of IBS is considerable. These indirect medical costs are frequently compounded by the direct medical costs related to additional medical tests and the use of various medical and nonmedical remedies that may have limited impact. CIC is equally common; in another systematic review, Suares and Ford (3) reported a pooled prevalence of 14%, and also noted that constipation was more common in females, in older subjects, and those of lower socioeconomic status (3). Chronic constipation has also been linked to impaired quality of life (4), most notably among the elderly (5). Neither IBS nor CIC are associated with abnormal radiologic or endoscopic abnormalities, nor are they associated with a reliable biomarker; diagnosis currently rests entirely, therefore, on clinical grounds. Although a number of clinical definitions of both IBS and CIC have been proposed, the criteria developed through the Rome process, currently in its third iteration, have been those most widely employed in clinical trials and, therefore, most relevant to any review of the literature on the management of these disorders. According to Rome III, IBS is defined on the basis of the presence of: Recurrent abdominal pain or discomfort at least 3 days/month in the past 3 months associated with two or more of the following: Improvement with defecation Onset associated with a change in frequency of stool Onset associated with a change in form (appearance) of stool These criteria should be fulfilled for the past 3 months with symptom onset at least 6 months before diagnosis (6). Rome III defines functional constipation as: the presence of two or more of the following: Straining during at least 25% of defecations Lumpy or hard stools in at least 25% of defecations Sensation of incomplete evacuation for at least 25% of defecations Sensation of anorectal obstruction/blockage for at least 25% of defecations Manual maneuvers to facilitate at least 25% of defecations (e.g., digital evacuation, support of the pelvic floor) Fewer than three defecations per week Furthermore, loose stools are rarely present without the use of laxatives and there are insufficient criteria for IBS. Again, these criteria should be fulfilled for the past 3 months with symptom onset at least 6 months before diagnosis (6). In Rome III, IBS is subtyped according to predominant bowel habit as IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed type (IBS-M), and unclassified (IBS-U). The definition of bowel habit type is, in turn, based on the patient's description of stool form by referring to the Bristol Stool Scale (7). The recognition that IBS sufferers segregate into subtypes according to predominant bowel habit, together with research findings suggesting that IBS-C and IBS-D may be pathophysiologically distinct entities (8,9,10), led to the development of therapies specifically directed at each of these subtypes. Nonetheless, it is worth noting that symptoms may not be stable over a lifetime and individuals may exhibit one IBS subtype during a period, and then a different IBS subtype during another period in their lives. However, although there is general awareness of the Rome criteria, they are infrequently employed in the assessment of IBS and CIC in clinical practice (11). To provide more "clinician friendly" definitions, as well as to permit inclusion of studies that predated the Rome process, American College of Gastroenterology Task Forces suggested the following definitions in prior systematic reviews: IBS is defined by: abdominal discomfort associated with altered bowel habits (12). Constipation is defined as: a symptom-based disorder defined as unsatisfactory defecation and is characterized by infrequent stools, difficult stool passage, or both. Difficult stool passage includes straining, a sense of difficulty passing stool, incomplete evacuation, hard/lumpy stools, prolonged time to stool, or need for manual maneuvers to pass stool. CIC is defined as the presence of these symptoms for at least 3 months (13). It is important to note that the Rome III criteria state that individuals with chronic constipation do not fulfill criteria for IBS, with pain or discomfort being a major determinant in the latter. In practice, a clear separation between CIC and IBS with constipation may be challenging and studies have shown, not only considerable overlap between these entities (14,15,16), but also a significant tendency for patients to migrate between these diagnoses over time (15). It is appropriate therefore that in this update of prior American College of Gastroenterology monographs on IBS and CIC, these entities be addressed in the same exercise (12,13,17). The goal of this exercise, therefore, was to update the most recent systematic reviews commissioned by the American College of Gastroenterology on IBS from 2009 (17) and CIC from 2005 (13). METHODS We have conducted a series of systematic reviews on the efficacy of therapy in IBS and CIC. There have been several systematic reviews of therapy for IBS and CIC published in the past 5 years (18,19,20,21,22). There have been considerable data published in the intervening time, and hence we have, therefore, updated all these systematic reviews of IBS and CIC and synthesized the data, including the information from new trials, where appropriate. The primary objective of this exercise was to assess the efficacy of available therapies in treating IBS and CIC compared with placebo or no treatment. The secondary objectives included assessing the efficacy of available therapies in treating IBS according to predominant stool pattern reported (IBS with constipation, IBS with diarrhea, and mixed IBS), as well as assessing adverse events with therapies for both IBS and CIC. Systematic review methodology We evaluated manuscripts that studied adults (aged >16 years) using any definition of IBS or CIC. For IBS, this included a clinician-defined diagnosis, the Manning criteria (23), the Kruis score (24), or Rome I (25), II (26), or III (6) criteria. For CIC, this included symptoms diagnosed by any of the Rome criteria (6,25,26), as well as a clinician-defined diagnosis. We included only parallel-group randomized controlled trials (RCTs) comparing active intervention with either placebo or no therapy. Crossover trials were eligible for inclusion, provided extractable data were provided at the end of the first treatment period, before crossover. For IBS, the following treatments were considered: Diet and dietary manipulation Fiber Interventions that modify the microbiota: probiotics, prebiotics, antibiotics Antispasmodics Peppermint oil Loperamide Antidepressants Psychological therapies, including hypnotherapy Serotonergic agents Prosecretory agents Polyethylene glycol For CIC, the following were considered: Fiber Osmotic and stimulant laxatives 5-HT4 agonists Prosecretory agents Biofeedback Bile acid transporter inhibitors Probiotics Subjects needed to be followed up for at least 1 week. To be eligible, trials needed to include one or more of the following outcome measures: Global assessment of improvement in IBS or CIC symptoms Improvement in abdominal pain for IBS Global IBS symptom or abdominal pain scores for IBS Mean number of stools per week during therapy for CIC Search strategy for identification of studies MEDLINE (1946 to October 2013), EMBASE and EMBASE Classic (1947 to October 2013), and the Cochrane central register of controlled trials were searched. Studies on IBS were identified with the terms irritable bowel syndrome and functional diseases, colon (both as medical subject headings (MeSH) and free text terms), and IBS, spastic colon, irritable colon, and functional adj5 bowel (as free text terms). For RCTs of dietary manipulation, these were combined using the set operator AND with studies identified with the terms: diet, fat-restricted, diet, protein-restricted, diet, carbohydrate-restricted, diet, gluten-free, diet, macrobiotic, diet, vegetarian, diet, Mediterranean, diet fads, gluten, fructose, lactose intolerance, or lactose (both as MeSH and free text terms), or the following free text terms: FODMAP$, glutens, food adj5 intolerance, food allergy, or food hypersensitivity. For RCTs of fiber, antispasmodics, and peppermint oil, these were combined using the set operator AND with studies identified with the terms: dietary fiber, cereals, psyllium, methylcellulose, sterculia, karaya gum, parasympatholytics, hyoscyamine, scopolamine, trimebutine, muscarinic antagonists, or butylscopolammonium bromide (both as MeSH and free text terms), or the following free text terms: bulking agent, psyllium fiber, fiber, husk, bran, ispaghula, wheat bran, calcium polycarbophil, spasmolytics, spasmolytic agents, antispasmodics, mebeverine, alverine, pinaverium bromide, otilonium bromide, cimetropium bromide, hyoscine butyl bromide, butylscopolamine, peppermint oil, or colpermin. For RCTs of probiotics, these were combined using the set operator AND with studies identified with the terms: Saccharomyces, Lactobacillus, Bifidobacterium, Escherichia coli, or probiotics (both as MeSH and free text terms). For RCTs of prebiotics and synbiotics, these were combined using the set operator AND with studies identified with the term: prebiotic (both MeSH and free text terms) or synbiotic (both MeSH and free text terms). For RCTs of antibiotics, these were combined using the set operator AND with studies identified with the terms: anti-bacterial agents, penicillins, cephalosporins, rifamycins, quinolones, nitroimidazoles, tetracycline, doxycycline, amoxicillin, ciprofloxacin, metronidazole, or tinidazole (both as MeSH and free text terms), or the following free text terms: antibiotic or rifamixin. For RCTs of loperamide, these were combined using the set operator AND with studies identified with the terms: loperamide or antidiarrheals (both as MeSH and free text terms), or the following free text terms: imodium or lopex. For RCTs of antidepressants and psychological therapies, including hypnotherapy, these were combined using the set operator AND with studies identified with the terms: psychotropic drugs, antidepressive agents, antidepressive agents (tricyclic), desipramine, imipramine, trimipramine, doxepin, dothiepin, nortriptyline, amitriptyline, selective serotonin reuptake inhibitors, paroxetine, sertraline, fluoxetine, citalopram, venlafaxine, cognitive therapy, psychotherapy, behavior therapy, relaxation techniques, or hypnosis (both as MeSH and free text terms), or the following free text terms: behavioral therapy, relaxation therapy, or hypnotherapy. For RCTs of serotonergic agents, these were combined using the set operator AND with studies identified with the terms: serotonin antagonists, serotonin agonists, cisapride, receptors (serotonin, 5-HT3), or receptors (serotonin, 5-HT4) (both as MeSH and free text terms), or the following free text terms: 5-HT3, 5-HT4, alosetron, cilansetron, ramosetron, prucalopride, mosapride, or renzapride. For RCTs of pro-secretory agents, these were combined using the set operator AND with studies identified with the following free text terms: linaclotide or lubiprostone. For RCTs of polyethylene glycol (PEG), these were combined using the set operator AND with studies identified with the term polyethylene glycol (both as a MeSH and free text term). Studies on CIC were identified with the terms constipation or gastrointestinal transit (both as MeSH and free text terms), or functional constipation, idiopathic constipation, chronic constipation, or slow transit (as free text terms). For the search involving biofeedback, the free text terms dyssynergia, pelvic floor dysfunction, anismus, and outlet obstruction were also added. For RCTs of fiber, these were combined using the set operator AND with studies identified with the terms: dietary fiber, cellulose, plant extracts, psyllium, cereals, plantago, or methylcellulose (both as MeSH and free text terms), or the following free text terms: fiber, soluble fiber, insoluble fiber, bran, ispaghula, metamucil, fybogel, or ispaghula. For RCTs of osmotic and stimulant laxatives, these were combined using the set operator AND with studies identified with the terms: laxatives, cathartics, anthraquinones, phenolphthaleins, indoles, phenols, lactulose, polyethylene glycol, senna plant, senna extract, bisacodyl, phosphates, dioctyl sulfosuccinic acid, magnesium, magnesium hydroxide, sorbitol, poloxamer (both as MeSH and free text terms), or the following free text terms: sodium picosulphate, docusate, milk of magnesia, danthron, senna, and poloxalkol. For RCTs of 5-HT4 agonists, these were combined using the set operator AND with studies identified with the terms: serotonin agonists, receptors, or serotonin, 5-HT4 (both as MeSH and free text terms), or the following free text terms: prucalopride, velusetrag, or naronapride. For RCTs of pro-secretory agents, these were combined using the set operator AND with studies identified with the following free text terms: lubiprostone or linaclotide. For RCTs of biofeedback, these were combined using the set operator AND with studies identified with the MESH terms biofeedback and psychology and the following free text terms: biofeedback or neuromuscular training. For RCTs of bile acid transporter inhibitors, these were combined using the set operator AND with studies identified with the following free text terms: bile acid transporter, elobixibat, or A3309. For RCTs of probiotics, these were combined using the set operator AND with studies identified with the terms: Saccharomyces, Lactobacillus, Bifidobacterium, E. coli, or probiotics (both as MeSH and free text terms). For RCTs of prebiotics and synbiotics, these were combined using the set operator AND with studies identified with the term: prebiotic (both MESH and free text terms) or synbiotic (both MESH and free text terms). The search was limited to humans. No restrictions were applied with regard to language of publication. A recursive search of the bibliography of relevant articles was also conducted. DDW (Digestive Diseases Week) and UEGW (United European Gastroenterology Week) abstract books were hand searched between 2000 and 2013. Authors of trial reports that did not give enough detail for adequate data extraction were contacted and asked to contribute full data sets. Experts in the field were contacted for leads on unpublished studies. Trials were assessed for risk of bias according to the methods described in the Cochrane handbook [27] using the following characteristics: method used to generate the randomization schedule, method used to conceal treatment allocation, implementation of masking, completeness of follow-up, and conduct of an intention-to-treat analysis. Eligibility, quality, and outcome data were extracted by the lead reviewer (Alexander Ford) and by a masked second reviewer (Paul Moayyedi) on to specially developed forms. Any discrepancy was resolved by discussion between the two reviewers in order to reach a consensus. Data were extracted as intention-to-treat analyses, where all dropouts were assumed to be treatment failures, wherever trial reporting allowed this. Data synthesis For IBS, whenever possible, any improvement of global IBS symptoms as a binary outcome was taken as the primary outcome measure. If this was not available, improvement in abdominal pain was used. For CIC, any improvement of global CIC symptoms as a binary outcome was taken as the primary outcome measure. The impact of interventions was expressed as a relative risk (RR) of IBS or CIC symptoms not improving, together with 95% confidence intervals (CIs). If there were sufficient data, RRs were combined using the DerSimonian and Laird random effects model (28) to give a more conservative estimate of the efficacy of individual IBS therapies. For continuous data, such as global IBS symptom scores or individual IBS symptom scores, a standardized mean difference, with 95% CIs, was calculated. It should be noted that some treatments may be beneficial in IBS or CIC because of the effects on outcomes other than global symptoms or abdominal pain, but this was not evaluated and was outside of the scope of this review. Tests of heterogeneity were reported (29). When the test of heterogeneity was significant (P<0.10 and/or I2>25%), the reasons for this were explored by evaluating differences in study population, study design, or study end points in subgroup analyses. Publication bias or other causes of small study effects were evaluated using tests for funnel plot asymmetry (30), where sufficient studies were identified (31). The number needed to treat (NNT), which is the number of patients who would need to receive active therapy, over and above the control therapy, for one to experience an improvement in symptoms, and the number needed to harm (NNH), which is the number of patients who would need to receive active therapy, over and above the control therapy, for one to experience an adverse event were calculated as the inverse of the risk difference from the meta-analysis and checked using the formula: NNT = 100 / RRR × BR, where BR is baseline risk and RRR is relative risk reduction. Methodology for assessing levels of evidence and grading recommendations We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system for grading the quality of evidence and strength of recommendation for each medical intervention (32). The system has been widely used in evidence-based guidelines and is endorsed by all major gastrointestinal societies (http://www.gradeworkinggroup.org). The quality of the evidence is based on the study design, as well as the extent of risk of bias, inconsistency, indirectness, imprecision, and publication bias that exists for the evidence supporting the intervention (33). Quality of evidence is described as high to very low, depending on the extent to which further evidence would change the estimate of treatment effect (Box 1). The grading scheme also classifies recommendations as strong or weak, according to the quality of the evidence, applicability to all patient groups, balance of benefits and risks, patient preferences, and cost. With this graded recommendation, the clinician receives guidance about whether or not recommendations should be applied to most patients, and whether or not recommendations are likely to change in the future after production of new evidence. "Strong" recommendations represent a "recommendation that can apply to most patients in most circumstances and further evidence is unlikely to change our confidence in the estimate of treatment effect." The summary of the evidence for IBS is presented in Table 1, the reasons for the decision on the quality of that evidence in Table 2, and the reasons for the strength of recommendation in Table 3. Similarly, the summary of the evidence for CIC is presented in Table 4, the reasons for the decision on quality of the evidence in Table 5, and the reasons for the strength of recommendation in Table 6.Box 1.: Interpretation of the grading of the quality of evidenceTable 1: Summary of results of monograph on interventions for IBSTable 2: Reasons for quality of evidence of assessment for IBS data according to GRADE criteriaTable 2: Continued.Table 3: Reasons for strength of recommendation for IBS therapies according to GRADE criteriaTable 4: Summary of results of monograph on interventions for CICTable 5: Reasons for quality of evidence of assessment of data on CIC according to GRADE criteriaTable 6: Reasons for strength of recommendation for treatments of CIC according to GRADE criteriaRESULTS Irritable bowel syndrome 1. Diet and dietary manipulation in IBS (a) Role of diet in IBS: Although food intake is one of the most common precipitants of symptoms in IBS (34), responses to food and with of the diet have not typically in the of a on their IBS sufferers have their to this or guidance from dietary IBS patients that they have an to although food are in IBS although the prevalence of food in societies is between 1 and in of gastrointestinal patients that that their symptoms food or food IBS symptoms to represent food intolerance, although only of patients can the food in a on their with and a of objective evidence to a studies have that a of IBS patients dietary to an extent that may their Role of dietary manipulation in may symptoms in individual IBS Quality of very We identified RCTs that evaluated dietary intervention in IBS to data of relevant symptom data and an intervention week three RCTs involving patients The first of these addressed the impact of in IBS. In a patients with IBS were randomized to either on a diet or to receive of on of an In the reported that their symptoms were not controlled as compared with in the placebo symptom scores for abdominal pain, with stool and were in those who a The second of these studies the of food or as not by but by In a parallel-group IBS patients were randomized to either an diet based on the presence of to various or a were followed for and symptoms assessed using a global impact score and the IBS with in the diet in the diet intervention noted a significant improvement in The reported in those with high to their The third study the of and IBS patients were randomized to a diet or their diet for those randomized to the diet, reported adequate control of their symptoms compared with of the diet Stool did not between stool frequency was in the diet A significant of this study was the of the dietary the of dietary in the of symptoms, or in the of IBS, is being To two and have been addressed in clinical trials, although it is that other (e.g., of and with the may also be relevant to the effects of food or food the that any of the of an diet or of a food in IBS the data provide limited guidance on the of diet in the management of IBS. and but their in the management of IBS need to be Fiber in IBS Fiber symptom in IBS. Quality of but not bran, symptom in IBS. Quality of intake of dietary is frequently to bowel for IBS, for However, insoluble frequently and abdominal In our prior systematic review we identified two additional studies for a of RCTs involving but trials did not IBS by subtype and only two to IBS-C In the study to patients, of were IBS-C and were were randomized to one of three of the soluble psyllium, of the insoluble bran, or of a placebo for the first a of patients psyllium, but not bran, reported adequate symptom for at least compared with placebo psyllium 95% was more than placebo during the third of treatment only 3 months of symptom in the psyllium was by points compared with points in the placebo and points in the No differences were with to quality of was most common in the most because of in IBS. Data on adverse events were only provided by trials These trials evaluated patients, but as of adverse events were small in 5 of the trials, of data was not A of of patients reported adverse events compared with of in the placebo Although its use in the management of IBS is time the status of fiber, in in IBS, is from may symptoms and provide soluble and psyllium, in provide in IBS. These effects to benefits in terms of of 3. Interventions that modify the microbiota: probiotics, prebiotics, and antibiotics The that the be relevant to IBS first from the that a although of individuals who an of on to IBS IBS Although has been linked to and and in the have been described in IBS, the of the to or other symptoms in IBS, is although both small and and in the have also been linked to IBS the of to IBS and findings in to the in patient probiotics, and have been used for on an basis by IBS they have only been to in clinical The of studies in IBS challenging as studies have employed different and in various patient and in Although the suggested that more than of all IBS sufferers studies have, in to such a high prevalence of in IBS These results may to to the test that may provide an of the this provided a for assessing antibiotics in IBS. a has efficacy in clinical trials in and although significant were over placebo in global IBS symptoms as well as in it is important to note that tests for were not in these trials, the of of in IBS (a) and in IBS: There is insufficient evidence to prebiotics or in IBS. Quality of very Probiotics in as a probiotics global symptoms, and in IBS.

Some Patients With Irritable Bowel Syndrome May Have Exocrine Pancreatic Insufficiency

The symptoms of irritable bowel syndrome (IBS) lead to considerable impairment of health-related quality of life and high health care costs. Available therapies are not efficient in treating the symptoms of IBS. Studies have shown the beneficial effects of Saccharomyces cerevisiae CNCM I-3856. Therefore, this study was done to evaluate the efficacy and safety of S. cerevisiae CNCM I-3856 in the treatment of IBS. This was a prospective, randomized, placebo-controlled study. One hundred newly diagnosed subjects with IBS were subgrouped into IBS-D, IBS-C, and IBS-M and then randomized to the S. cerevisiae CNCM I-3856 and placebo groups. Saccharomyces cerevisiae/placebo was administered in addition to standard treatment for a period of 8weeks. Subjects were assessed for improvement of abdominal pain and change in stool consistency using a 7-point Likert scale and Bristol stool scale respectively. The mean reduction of abdominal pain score in the S. cerevisiae CNCM I-3856 group was statistically significant when compared with the placebo group (p < 0.001). Similar improvement was also seen in the subgroups. Improvement in stool consistency in IBS-D subgroup at the end of treatment period was found to be statistically significant in S. cerevisiae group when compared to that of placebo (p < 0.001). A similar improvement was seen in the IBS-C and IBS-M subgroups. No serious adverse events were recorded in both groups. The use of Saccharomyces cerevisiae CNCM I-3856 in IBS at a dose of 2 billion CFU twice daily for 8weeks has shown to have an improvement in abdominal pain and stool consistency due to its analgesic and anti-inflammatory activity in subjects with IBS.

Introduction: Eluxadoline, a mixed μ-opioid receptor (OR) and κ-OR agonist and δ-OR antagonist that is locally active in the gastrointestinal tract, is approved for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults. In two Phase 3 studies, eluxadoline significantly improved symptoms of IBS-D based on a composite endpoint of simultaneous improvement in stool consistency and abdominal pain scores. Post hoc analyses of pooled data from these trials were conducted to further evaluate the impact of baseline abdominal pain severity on treatment outcomes. Methods: Two double-blind, placebo-controlled, Phase 3 trials (IBS-3001 and IBS-3002) randomized patients meeting Rome III criteria for IBS-D to twice daily treatment with eluxadoline 75 or 100 mg or placebo. Patients rated IBS symptoms daily, including worst abdominal pain (WAP, 0-10 scale) and stool consistency (Bristol Stool Scale [BSS]). The primary efficacy endpoint was composite response, based on simultaneous daily improvement of ≥30% in WAP score vs. baseline and BSS score < 5 with ≥50% of days demonstrating a response, evaluated over 12 and 26 weeks. The Irritable Bowel Syndrome Quality of Life instrument was assessed at baseline, Week 4, and each subsequent visit. Pooled data were stratified by baseline abdominal pain score ( < 5; 5-< 8; ≥8) and composite, abdominal pain, and stool consistency responder rates over Weeks 1-12 and 1-26 were calculated. Statistical inferences were not made due to this being a post hoc analysis and the small sample size of patients with baseline abdominal pain score ≥8.Table 1Results: 2428 IBS-D patients were enrolled across both trials. Proportions of composite, abdominal pain, and stool consistency responders with eluxadoline were greater than with placebo in the overall population and in all baseline abdominal pain severity subgroups over Weeks 1-12 and 1-26 (Table). Responder rates for composite, stool consistency, and abdominal pain decreased with increasing baseline abdominal pain severity, with differences from placebo largest for patients with the lowest category of abdominal pain. Conclusion: Greater numbers of patients show a composite, abdominal pain, and stool consistency response with eluxadoline vs. placebo across baseline abdominal pain severity categories. This work was funded by Allergan plc.

Purpose: To examine clinical practice effectiveness of a medical food containing serum-derived bovine immunoglobulin (SBI) for the management of symptoms in irritable bowel syndrome with diarrhea (IBS-D) patients. Methods: From 165 IBS-D patient medical charts [mean age=59.6 years (range: 19-98), female (n=109), Caucasian (n=144)], recorded daily stools/consistency, abdominal pain, and patient/ physician reported quality of life (QoL) scores were retrospectively collected on those prescribed SBI for a minimum of 8 weeks. A generalized estimating equations model was used to analyze and compare changes for scores of symptoms and QoL. Results: Where data existed in charts, 46% of patients on SBI had a combined mean score reduction in daily stools, improvement in stool consistency (Bristol Stool Scale from >5 to <5) and decrease in abdominal pain (?30%). Significant improvements (p<0.001) in individual symptom and QoL scores with a high response were also reported for daily stools (76%), consistency (78%), abdominal pain (69%), as well as patient (79%) and physician QoL (73%). Eleven patients experienced 13 adverse events (AEs) while receiving SBI with nausea (n=6) most prevalent. No serious AEs were reported, but 4 patients discontinued SBI. Conclusion: In this retrospective chart analysis of IBS-D patients who took a medical food containing SBI for 8 weeks, there were statistical improvements in daily stool number, stool consistency, abdominal pain and QoL scores supporting its use IBS-D.

Purpose: To examine clinical practice effectiveness of a medical food containing serum-derived bovine immunoglobulin (SBI) for the management of symptoms in irritable bowel syndrome with diarrhea (IBS-D) patients. Methods: From 165 IBS-D patient medical charts [mean age=59.6 years (range: 19-98), female (n=109), Caucasian (n=144)], recorded daily stools/consistency, abdominal pain, and patient/ physician reported quality of life (QoL) scores were retrospectively collected on those prescribed SBI for a minimum of 8 weeks. A generalized estimating equations model was used to analyze and compare changes for scores of symptoms and QoL. Results: Where data existed in charts, 46% of patients on SBI had a combined mean score reduction in daily stools, improvement in stool consistency (Bristol Stool Scale from >5 to <5) and decrease in abdominal pain (?30%). Significant improvements (p<0.001) in individual symptom and QoL scores with a high response were also reported for daily stools (76%), consistency (78%), abdominal pain (69%), as well as patient (79%) and physician QoL (73%). Eleven patients experienced 13 adverse events (AEs) while receiving SBI with nausea (n=6) most prevalent. No serious AEs were reported, but 4 patients discontinued SBI. Conclusion: In this retrospective chart analysis of IBS-D patients who took a medical food containing SBI for 8 weeks, there were statistical improvements in daily stool number, stool consistency, abdominal pain and QoL scores supporting its use IBS-D.

Introduction: IBS-D is a common condition with few effective treatment options. The prescription medical food, SBI, has been shown to manage chronic loose and frequent stools in IBS-D patients. The safety and effectiveness of SBI as a therapy for IBS-D was further examined in this multi-center, IRB-reviewed study for overall and individual symptom response. Methods: Symptom data including stool frequency and consistency (Bristol Stool Scale 1-7), abdominal pain intensity (0 = no pain to 10 = worst pain) and adverse events (AEs) were collected from medical charts on 116 patients. Criteria for inclusion in primary analysis were patients having baseline recorded scores for stool consistency and abdominal pain, failure of standard-of-care (SOC) treatment, and not having received confounding IBS-D medications while on SBI. Results: The majority of patients who met criteria for analysis (n = 34) were white (94%), female (71%) with a median age of 53 (28, 85) and received SBI therapy for a mean duration of 23.2±24.1 wks [median 15.5 wks (0.4, 97.9)]. Mean baseline symptom scores were: stool frequency 5.24 (range 2 to 20); stool consistency 6.00 (range 4 to 7) and abdominal pain 4.56 (range 2 to 10). Twenty-five of the 34 patients had baseline abdominal pain scores >2 and stool consistency scores ≥ 5 to assess overall response; nine patients were excluded based on absence of pain (recorded score = 0) and normal stool score (Bristol Stool Scale = 4) at baseline. Of the 25 patients, 16 (64%) were responders with stool consistency < 5 and a 30% reduction in abdominal pain scores following SBI therapy. Using a generalized linear regression model for individual symptoms, the number of stools per day decreased by 3.24 (95% Confidence Interval (CI) 0.50, 5.98; P = 0.022), stool consistency improved by 1.86 (95% CI, 1.39, 2.33; P < 0.0001) and abdominal pain/discomfort intensity decreased by 3.03 (95% CI 1.668, 4.39; P < 0.0001). Thirteen of the 116 patients experienced one or more AEs while on SBI therapy. The main AEs were nausea (n = 5 patients) and an increase abdominal discomfort (n = 2 patients). No serious AEs were reported. Conclusion: Though retrospective, the inclusion criteria of SOC failure prior to SBI administration with demonstrated high combined abdominal pain and stool consistency response, as well as statistically significant individual symptom improvement, demonstrate SBI's clinical utility in IBS-D management. Additional chart reviews continue.

Immune Activation in Patients With Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) causes gastrointestinal symptoms such as abdominal pain, bloating, and bowel pattern abnormalities, which compromise patients’ daily functioning. Common therapies address one or two IBS symptoms, while others offer wider symptom control, presumably by targeting pathophysiologic mechanisms of IBS. The aim of this targeted literature review was to capture clinical trial reports of agents receiving the highest recommendation (Grade 1) for treatment of IBS from the 2009 American College of Gastroenterology IBS Task Force, with an emphasis on diarrhea-predominant IBS. Literature searches in PubMed captured articles detailing randomized placebo-controlled trials in IBS/diarrhea-predominant IBS for agents receiving Grade I (strong) 2009 American College of Gastroenterology IBS Task Force recommendations: tricyclic antidepressants, nonabsorbable antibiotics, and the 5-HT3 receptor antagonist alosetron. Studies specific for constipation-predominant IBS were excluded. Tricyclic antidepressants appear to improve global IBS symptoms but have variable effects on abdominal pain and uncertain tolerability; effects on stool consistency, frequency, and urgency were not adequately assessed. Nonabsorbable antibiotics show positive effects on global symptoms, abdominal pain, bloating, and stool consistency but may be most efficacious in patients with altered intestinal microbiota. Alosetron improves global symptoms and abdominal pain and normalizes bowel irregularities, including stool frequency, consistency, and fecal urgency. Both the nonabsorbable antibiotic rifaximin and the 5-HT3 receptor antagonist alosetron improve quality of life. Targeted therapies provide more complete relief of IBS symptoms than conventional agents. Familiarization with the quantity and quality of evidence of effectiveness can facilitate more individualized treatment plans for patients with this heterogeneous disorder.