Shanti L. Eswaran

Irritable Bowel Syndrome: A Clinical Review

IMPORTANCE Irritable bowel syndrome (IBS) affects 7% to 21% of the general population. It is a chronic condition that can substantially reduce quality of life and work productivity. OBJECTIVES To summarize the existing evidence on epidemiology, pathophysiology, and diagnosis of IBS and to provide practical treatment recommendations for generalists and specialists according to the best available evidence. EVIDENCE REVIEW A search of Ovid (MEDLINE) and Cochrane Database of Systematic Reviews was performed for literature from 2000 to December 2014 for the terms pathophysiology, etiology, pathogenesis, diagnosis, irritable bowel syndrome, and IBS. The range was expanded from 1946 to December 2014 for IBS, irritable bowel syndrome, diet, treatment, and therapy. FINDINGS The database search yielded 1303 articles, of which 139 were selected for inclusion. IBS is not a single disease but rather a symptom cluster resulting from diverse pathologies. Factors important to the development of IBS include alterations in the gut microbiome, intestinal permeability, gut immune function, motility, visceral sensation, brain-gut interactions, and psychosocial status. The diagnosis of IBS relies on symptom-based criteria, exclusion of concerning features (symptom onset after age 50 years, unexplained weight loss, family history of selected organic gastrointestinal diseases, evidence of gastrointestinal blood loss, and unexplained iron-deficiency anemia), and the performance of selected tests (complete blood cell count, C-reactive protein or fecal calprotectin, serologic testing for celiac disease, and age-appropriate colorectal cancer screening) to exclude organic diseases that can mimic IBS. Determining the predominant symptom (IBS with diarrhea, IBS with constipation, or mixed IBS) plays an important role in selection of diagnostic tests and treatments. Various dietary, lifestyle, medical, and behavioral interventions have proven effective in randomized clinical trials. CONCLUSIONS AND RELEVANCE The diagnosis of IBS relies on the identification of characteristic symptoms and the exclusion of other organic diseases. Management of patients with IBS is optimized by an individualized, holistic approach that embraces dietary, lifestyle, medical, and behavioral interventions.

Fiber and functional gastrointestinal disorders.

Despite years of advising patients to alter their dietary and supplementary fiber intake, the evidence surrounding the use of fiber for functional bowel disease is limited. This paper outlines the organization of fiber types and highlights the importance of assessing the fermentation characteristics of each fiber type when choosing a suitable strategy for patients. Fiber undergoes partial or total fermentation in the distal small bowel and colon leading to the production of short-chain fatty acids and gas, thereby affecting gastrointestinal function and sensation. When fiber is recommended for functional bowel disease, use of a soluble supplement such as ispaghula/psyllium is best supported by the available evidence. Even when used judiciously, fiber can exacerbate abdominal distension, flatulence, constipation, and diarrhea.

Food: The Forgotten Factor in the Irritable Bowel Syndrome

After years of inattention, there is a growing body of evidence to suggest that dietary constituents at least exacerbate symptoms and perhaps contribute to the pathogenesis of the irritable bowel syndrome (IBS). Although patients with IBS self-report food allergies more often than the general population, the evidence suggests that true food allergies are relatively uncommon. Less clearly defined food intolerances may be an important contributor to symptoms in IBS patients. This article reviews the literature supporting a causal link between food and the symptoms of IBS as well as the evidence supporting dietary interventions as a means of managing IBS symptoms.

A Randomized Controlled Trial Comparing the Low FODMAP Diet vs. Modified NICE Guidelines in US Adults with IBS-D

Objectives:There has been an increasing interest in the role of fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) in irritable bowel syndrome (IBS). We report results from the first randomized controlled trial of the low FODMAP diet in US adults with IBS and diarrhea (IBS-D). The objectives were to compare the efficacy of the low FODMAP diet vs. a diet based upon modified National Institute for Health and Care Excellence guidelines (mNICE) on overall and individual symptoms in IBS-D patients.Methods:This was a single-center, randomized-controlled trial of adult patients with IBS-D (Rome III) which compared 2 diet interventions. After a 2-week screening period, eligible patients were randomized to a low FODMAP or mNICE diet for 4 weeks. The primary end point was the proportion of patients reporting adequate relief of IBS-D symptoms ≥50% of intervention weeks 3–4. Secondary outcomes included a composite end point which required response in both abdominal pain (≥30% reduction in mean daily pain score compared with baseline) and stool consistency (decrease in mean daily Bristol Stool Form of ≥1 compared with baseline), abdominal pain and stool consistency responders, and other key individual IBS symptoms assessed using daily questionnaires.Results:After screening, 92 subjects (65 women, median age 42.6 years) were randomized. Eighty-four patients completed the study (45 low FODMAP, 39 mNICE). Baseline demographics, symptom severity, and nutrient intake were similar between groups. Fifty-two percent of the low FODMAP vs. 41% of the mNICE group reported adequate relief of their IBS-D symptoms (P=0.31). Though there was no significant difference in the proportion of composite end point responders (P=0.13), the low FODMAP diet resulted in a higher proportion of abdominal pain responders compared with the mNICE group (51% vs. 23%, P=0.008). Compared with baseline scores, the low FODMAP diet led to greater reductions in average daily scores of abdominal pain, bloating, consistency, frequency, and urgency than the mNICE diet.Conclusions:In this US trial, 40–50% of patients reported adequate relief of their IBS-D symptoms with the low FODMAP diet or a diet based on modified NICE guidelines. The low FODMAP diet led to significantly greater improvement in individual IBS symptoms, particularly pain and bloating, compared with the mNICE diet.

Endoscopic findings and clinical outcomes in ventricular assist device recipients with gastrointestinal bleeding

BackgroundGastrointestinal bleeding (GIB) is an important clinical problem in recipients of ventricular assist devices (VAD), although data pertaining to the endoscopic evaluation and management of this complication are limited in the medical literature.AimsWe sought to identify the most common endoscopic findings in VAD recipients with GIB, and to better define the diagnostic and therapeutic utility of endosopy for this patient population.MethodsTwenty-six subjects with VAD and overt GIB were retrospectively identified. Clinical and endoscopic data were abstracted for each subject on to standardized forms in duplicate and independent fashion. Raw data and descriptive statistics were reported.ResultsNon-peptic vascular lesions were the most common cause of GIB. A definitive cause of bleeding was identified by endoscopy in almost 60% of subjects. Endoscopic hemostasis was achieved in 14/15 patients in whom bleeding did not stop spontaneously. Rebleeding occurred in 50% of subjects and was successfully retreated or stopped spontaneously in all cases. Colonoscopy did not establish a definitive diagnosis or deliver hemostatic therapy in any case.ConclusionsVascular malformations account for the overwhelming majority of bleeding lesions in VAD patients with GIB. Endoscopy seems to be a safe and effective tool for diagnosing, risk stratifying, and treating this patient population, although multiple endoscopies may be necessary before therapeutic success, and the incidence of rebleeding is high. A prospective multi-center registry is necessary to establish evidence-based management algorithms for VAD recipients with GIB.

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

Opinion StatementThe 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.

A Diet Low in Fermentable Oligo-, Di-, and Monosaccharides and Polyols Improves Quality of Life and Reduces Activity Impairment in Patients With Irritable Bowel Syndrome and Diarrhea

BACKGROUND & AIMS: We investigated the effects of a diet low in fermentable oligo‐, di‐, and monosaccharides and polyols (FODMAPs) vs traditional dietary recommendations on health‐related quality of life (QOL), anxiety and depression, work productivity, and sleep quality in patients with irritable bowel syndrome and diarrhea (IBS‐D). METHODS: We conducted a prospective, single‐center, single‐blind trial of 92 adult patients with IBS‐D (65 women; median age, 42.6 years) randomly assigned to groups placed on a diet low in FODMAPs or a modified diet recommended by the National Institute for Health and Care Excellence (mNICE) for 4 weeks. IBS‐associated QOL (IBS‐QOL), psychosocial distress (based on the Hospital Anxiety and Depression Scale), work productivity (based on the Work Productivity and Activity Impairment), and sleep quality were assessed before and after diet periods. RESULTS: Eighty‐four patients completed the study (45 in the low‐FODMAP group and 39 in the mNICE group). At 4 weeks, patients on the diet low in FODMAPs had a larger mean increase in IBS‐QOL score than did patients on the mNICE diet (15.0 vs 5.0; 95% CI, –17.4 to –4.3). A significantly higher proportion of patients in the low‐FODMAP diet group had a meaningful clinical response, based on IBS‐QOL score, than in the mNICE group (52% vs 21%; 95% CI, –0.52 to –0.08). Anxiety scores decreased in the low‐FODMAP diet group compared with the mNICE group (95% CI, 0.46–2.80). Activity impairment was significantly reduced with the low‐FODMAP diet (–22.89) compared with the mNICE diet (–9.44; 95% CI, 2.72–24.20). CONCLUSIONS: In a randomized, controlled trial, a diet low in FODMAPs led to significantly greater improvements in health‐related QOL, anxiety, and activity impairment compared with a diet based on traditional recommendations for patients with IBS‐D. ClinicalTrials.gov, number NCT01624610.

Emerging Pharmacologic Therapies for Constipation-predominant Irritable Bowel Syndrome and Chronic Constipation

Irritable bowel syndrome with constipation and chronic functional constipation are common digestive disorders that negatively impact quality of life and account for billions of dollars in health care costs. Related to the heterogeneity of pathogenesis that underlie these disorders and the failure of symptoms to reliably predict underlying pathophysiology, traditional therapies provide relief to only a subset of affected individuals. The evidence surrounding new and emerging pharmacologic treatments, which include both luminally and systemically acting drugs, is discussed here. These include agents such as lubiprostone, bile acid modulations, guanylate cyclase-C receptor agonists, serotonin receptor modulators and herbal therapies.

821 A Low FODMAP Diet Improves Quality of Life, Reduces Activity Impairment, and Improves Sleep Quality in Patients With Irritable Bowel Syndrome and Diarrhea: Results From a U.S. Randomized, Controlled Trial

Background: In addition to characteristic GI symptoms, irritable bowel syndrome (IBS) patients have incraesed psychological comorbidity and sleep disturbance as well as reduced health-related quality of life (HRQOL), and work productivity relative to the general population. We assessed the impact of a low FODMAP diet versus a control diet on HRQOL, psychological distress, work productivity, and sleep quality measures in patients with IBS and diarrhea (IBS-D). Methods: We conducted a prospective, single center, single-blind randomized controlled trial of adult patients with IBS-D (Rome III). After completing a 2week screening period, eligible patients (mean daily abdominal pain score ≥4 & Bristol stool scale score of ≥5) were randomized to 4-weeks of a low FODMAP diet (LFD) or a control diet based upon modified NICE guidelines. Foods containing FODMAPs were not specifically excluded from the control diet. Both dietary interventions were administered by experienced research dietitians. HRQOL (IBS-QOL), psychosocial distress (Hospital Anxiety and Depression Scale (HADS)), work productivity (Workplace Activity Impairment (WPAI)), and an assessment of sleep quality were conducted before and after the dietary intervention. Fatigue and sleep quality were assessed daily over the study period. Results: Of the 171 subjects consented for enrollment, 92 (65 women (71%), median age 42.6 years (range = 19 -75 years), 68 Caucasian (74%)) were eligible for randomization based upon the baseline assessment. Eighty-three patients completed the study period (45 LFD, 38 control). Demographics, baseline symptom severity, and baseline HRQOL measures were similar between groups. Baseline energy, nutrient, and FODMAP intake were similar between groups. At 4 weeks, the proportion of patients with a >10-point improvement in IBS-QOL score was significantly greater in the LFD group compared to the control group (58% v 24%, p=0.0032). Similarly, the mean total IBS-QOL score at 4 weeks was higher in the LFD v control (p=.0228). Significant improvements were observed in several IBS-QOL domains ( Table 1). There was a trend towards improvement in anxiety for the LFD vs. the control diet which did not reach statistical significance (7.73 v 9.26, p=0.0679). For WPAI, only activity impairment significantly improved (LFD 29.29 v control 41.90, p=0.0398). There was no difference between the two groups for fatigue but sleep quality improved in the LFD compared to the control diet (6.33 v 7.46, p=0.0336). Conclusion: In this US randomized, controlled study of IBS-D patients, a low FODMAP diet improved HRQOL, activity impairment, and sleep quality when compared to a control diet. This is one of the first methodologically rigorous clinical trials to show that diet-based therapy can not only improve symptoms but also HRQOL in patients with IBS-D. Table. IBS QOL means after dietary intervention.

Increased Prevalence of Rare Sucrase-isomaltase (SI) Pathogenic Variants in Irritable Bowel Syndrome Patients

&NA; Patients with irritable bowel syndrome (IBS) often associate their symptoms to certain foods. In congenital sucrase‐isomaltase deficiency (CSID), recessive mutations in the SI gene (coding for the disaccharidase digesting sucrose and 60% of dietary starch)1 cause clinical features of IBS through colonic accumulation of undigested carbohydrates, triggering bowel symptoms.2 Hence, in a previous study,3 we hypothesized that CSID variants reducing SI enzymatic activity may contribute to development of IBS symptoms. We detected association with increased risk of IBS for 4 rare loss‐of‐function variants typically found in (homozygous) CSID patients, because carriers (heterozygous) of these rare variants were more common in patients than in controls.1,4 Through a 2‐step computational and experimental strategy, the present study aimed to determine whether other (dys‐)functional SI variants are associated with risk of IBS in addition to known CSID mutations. We first aimed to identify all SI rare pathogenic variants (SI‐RPVs) on the basis of integrated Mendelian Clinically Applicable Pathogenicity (M‐CAP) and Combined Annotation Dependent Depletion (CADD) predictive (clinically relevant) scores; next, we inspected genotype data currently available for 2207 IBS patients from a large ongoing project to compare SI‐RPV case frequencies with ethnically matched population frequencies from the Exome Aggregation Consortium (ExAC).