Functional Bowel Disease Research Articles

Submitted, Not Presented: Clinical Vignettes/Case Reports - Functional Bowel Disease.

Submitted, Not Presented: Clinical Vignettes/Case Reports - Functional Bowel Disease.

Basic Science Luminal.

Basic Science Luminal.

Prevalence and Predictors of Bowel Incontinence: Results from a US Population-Based Study 2016 ACG Category Award (Functional Bowel Disease): 2016 ACG Presidential Poster Award

Introduction: Fecal incontinence (FI) is a prevalent disorder characterized by the uncontrolled passage of solid or liquid stool. The aim of this study was to determine the prevalence and predictors of FI in a large, representative sample of community-dwelling Americans. Methods: To evaluate the burden of gastrointestinal (GI) illness in the US, we conducted the National GI Survey in October 2015 using MyGiHealth, a mobile app that systematically collects patient GI symptoms. We partnered with Cint®, a survey research firm, to recruit a representative sample of Americans to complete MyGiHealth. MyGiHealth guided participants through NIH GI Patient Reported Outcome Measurement Information System (PROMIS®) surveys and questions about relevant comorbidities and demographics. FI was defined as accidental leakage of solid or liquid stool within the last seven days. Our primary and secondary outcomes were FI prevalence and FI severity (as determined by NIH PROMIS scores), respectively. Multivariable logistic and linear regression models were used to identify independent predictors of FI prevalence and severity, respectively. Results: Overall, 71,812 individuals completed the National GI Survey, of which 3,094 (4.3%) individuals reported FI. Older age, male gender and Hispanic ethnicity were demographic factors associated with a higher likelihood of FI (Table 1). Asian ethnicity reduced the likelihood of FI. Those who reported diarrhea or constipation in the last week, had Crohn's, ulcerative colitis, celiac disease (CD), irritable bowel syndrome and diabetes mellitus (DM) were all more likely to have FI. With respect to FI symptom severity, as determined by NIH PROMIS scores, more severe FI was seen among non-Hispanic blacks and Hispanics, whereas patients aged ≥65 years had less severe FI (Table 2). Participants who reported concomitant diarrhea, Crohn's, CD, DM, HIV/AIDS, and chronic idiopathic constipation also had more severe FI.Table 1: Predictors of having experienced bowel incontinence within the past 7 daysTable 1: Continued.Table 2: Factors associated with fecal incontinence severity by multivariable linear regressionTable 2: Continued.Conclusion: In this large population-based survey of community-dwelling Americans,FI prevalence was lower than prior estimates. FI is an age-related disorder found to be more prevalent in males and those of Hispanic ethnicity. Proactive screening for FI in Crohn's, CD, and DM is warranted and their presence is associated with more severe FI.

Common functional pain syndromes

### Key points When a patient presents with pain of no obvious organic origin, they are often labelled as having ‘functional’ pain. The exact diagnosis is derived from the organ system displaying the predominant symptoms e.g. musculoskeletal pain in fibromyalgia (FM) or visceral pain in irritable bowel syndrome (IBS). The worldwide prevalence of all functional pain syndromes (FPS) is 15–20%. World Health Organization (WHO) surveys reveal that ∼10% of primary care patients develop a chronic pain condition within 12 months of initial registration. Of these, at least 50% continue to have symptoms beyond 1 yr. FPS cause enormous economic burden on society with concurrent ramifications for the individual's family in particular and society in general. FM alone has been estimated to cost around £4000 per patient per year. There has been a paradigm shift in the understanding of FPS. The old model of multiple discrete chronic pain conditions is being replaced by a more overarching, although no less complex, state of central sensitivity syndrome (CSS). Evidence is being accrued that FPS represent the phenotypic output of a complex interplay between genetic susceptibility, gene–environment interactions, and environmental triggers. Four common FPS will be reviewed in this article: FM, IBS, temporomandibular dysfunction (TMD), and chronic cardiac chest pain (CCCP). The pathophysiology and management of each will be examined and the case presented for a shared underlying mechanism called CSS. Once this new mechanism is adopted more widely, it will allow for future novel management options to be …

Biochemical Profile of Nonalcoholic Fatty Liver Disease Patients in Eastern India with Histopathological Correlation.

Aminotransferase assay is often used as a screening test as well as an endpoint for resolution of disease in nonalcoholic fatty liver disease (NAFLD). Aim of the study was to evaluate the relationship of transaminase level with metabolic variables and histology in NAFLD. Single center observational study was conducted in a gastroenterology clinic at Cuttack in coastal Odisha. Subjects were consecutive patients presenting with functional bowel disease and undergoing abdominal sonography. All participants were evaluated for the presence of metabolic syndrome (MS), insulin resistance, liver function test and lipid profile. Various parameters were compared between NAFLD subjects and controls. 53.5% of NAFLD had normal serum transaminases, whereas 20.8% of healthy controls had transaminitis. NAFLD patients had significantly higher BMI, fasting plasma glucose, serum transaminases, serum triglycerides, serum insulin and homeostatic model assessment (HOMA) IR than controls. NAFLD patients who had transaminitis had significantly higher incidence of MS and higher mean HOMA IR than those without. There was no significant difference in histopathological features between NAFLD with and without transaminitis. To conclude, over half of NAFLD subjects do not have transaminitis while transaminitis is present in a fifth of healthy people without fatty liver. Hence serum transaminase should not be used as screening test for NAFLD. NAFLD patients with transaminitis had a higher incidence of MS and insulin resistance than those without. However, there was no significant difference in histopathological features between these two groups.

The overlap of upper functional gastrointestinal disorders with irritable bowel syndrome in Chinese outpatients: A multicenter study.

Irritable bowel syndrome (IBS) is a common functional bowel disease, and the overlap with upper functional gastrointestinal disorders (FGIDs) is popular. However, the coexistent upper GI symptom profiles, upper FGID spectra, and related risk factors among IBS subjects remain unclear in mainland of China. Consecutive patients from the outpatient gastroenterology clinics of three tertiary hospitals in China were enrolled in this multicenter study. All upper GI symptoms occurring at least once a week in the last 3 months were recorded. Diagnostic criteria of functional esophageal, gastroduodenal disorders and IBS were based on Rome III criteria. Risk factors were assessed using a multivariate logistic regression model. Of the 8906 consecutive patients, 751 patients met Rome III criteria for IBS and 735 IBS patients participated in the interview. Postprandial fullness (30.6%), belching (27.1%), and regurgitation (21.8%) were the three most prevalent upper GI symptoms in IBS. Functional dyspepsia (FD, 36.7%), belching disorders (27.1%), and functional heartburn (16.3%) were the three most frequent upper FGID in IBS patients. Female sex, divorced or widowed versus married status, defecation straining, reduced bowel movement, mixed IBS, abdominal distention, mild abdominal pain, moderate discomfort were positively associated with IBS-FD overlap. Female sex, drinking, moderate discomfort, and mild to moderate distension were independent risk factors for IBS-belching disorder overlap. The study provides detailed overlap spectra of upper FGID with IBS. Mixed IBS is an important risk factor for IBS-FD overlap, which deserved more concern.

PTU-125 Laboratory Investigations for Patients Meeting Diagnostic Criteria for Irritable Bowel Syndrome: Are We Meeting the Standards?

Introduction Alongside a thorough clinical assessment NICE clinical guideline 61 recommends that patients meeting diagnostic criteria for irritable bowel syndrome (IBS), as defined by the Rome III criteria, should undergo laboratory testing for inflammation (C-reactive peptide (CRP) and plasma viscosity (PV) or erythrocyte sedimentation rate (ESR)), full blood count (FBC) and antibody testing for coeliac disease to exclude non-organic pathology.1 Faecal calprotectin is a reliable and cost effective adjuvant test to help differentiate between functional and inflammatory bowel disease (IBD).2,3 Our aim was to assess local adherence to NICE guidelines on investigating patients who meet diagnostic criteria for IBS. Methods As part of a wider study into the use of faecal calprotectin as a diagnostic tool within Gloucestershire Hospitals NHS Foundation Trust, we interrogated clinic letters, endoscopy reports and pathology results for patients in whom a negative ( Results Of the 148 patients (age range: 16–81, median age: 35; 72% female) who satisfied inclusion criteria, 63.5% (n = 94) had not undergone at least one of the recommended laboratory tests around the time of faecal calprotectin measurement. PV/ESR had not been checked in a majority (54.1%). Notably, 7.4% of patients had never had coeliac serology checked, 72.7% of whom presented with a change in bowel habit. Conclusion Although clear guidance exists for the investigation of patients meeting diagnostic criteria for IBS and use of faecal calprotectin as a diagnostic tool, insufficient essential accessory investigations are being completed. This risks conditions such as IBD, gastrointestinal cancer and coeliac disease being misdiagnosed as IBS with significant implications for delays in management and ongoing avoidable morbidity. We are reviewing measures to improve local adherence to NICE guidance, and call on other Trusts nationally to reflect on their own practice. References 1 Irritable bowel syndrome in adults: diagnosis and management. NICE guidelines [CG61]. Published: February 2008. 2 Konikoff MR, Denson LA. Role of faecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease. Inflammatory Bowel Diseases 2006;12(6):524–34. 3 Faecal calprotectin diagnostic tests for inflammatory diseases of the bowel. NICE diagnostics guidance [DG11]. Published: October 2013. Disclosure of Interest None Declared

Rome IV—Functional GI Disorders: Disorders of Gut-Brain Interaction

Rome IV—Functional GI Disorders: Disorders of Gut-Brain Interaction

Tu1434 Response to a Diet Low in FODMAPs in Subtypes of Functional Bowel Disease After Nutrient Challenge Testing

Tu1434 Response to a Diet Low in FODMAPs in Subtypes of Functional Bowel Disease After Nutrient Challenge Testing

Two-Way Adjusting Effect Of Acupuncture On Tianshu (ST25) And Dachangshu (BL25) For Treating Functional Bowel Disease

Constipation and diarrhea is considered to be a pair of opposite states in functional bowel disease. The two-way adjusting effect is a very important mechanism of acupuncture. However, there is not enough evidence in clinical trials. This study was aimed to investigate the effects of two-way adjusting of acupuncture on Tianshu (ST25) and Dachangshu (BL25) for treating functional bowel disease (functional constipation and functional diarrhea). There are two groups in this trial, one is functional constipation group (36 patients) and the other is functional diarrhea group (30 patients). 16 times acupuncture were applied at Tianshu (ST25) and Dachangshu (BL25) in both two groups in 4 weeks. Defecation frequency and feces traits was the main evaluation index. After the treatment, defecation frequency was significantly increased, and feces traits turn soft in functional constipation group. But functional diarrhea group is the opposite. We conclude that acupuncture Tianshu (ST25) and Dachangshu (BL25) is effective to both constipation and diarrhea. These findings suggest that there is an affection of two-way adjusting in acupuncture.

Efficacy of Sparex in the management of intestinal motility disorders

Irritable bowel syndrome (IBS) is one of the most common functional bowel diseases. What is more, a number of digestive diseases are characterized by symptoms similar to those observed in IBS. The principles of treatment of IBS and IBS-related disorders are same. The key symptom of IBS - abdominal pain - is developed as a result of spasmodic or hyperkinetic dyskinesia, so the main group of drugs to be used in the treatment are antispasmodics. Preference is given to selective antispasmodics. Sparex is a national generic of the selective intestinal antispasmodic mebeverine hydrochloride which has been known since 1965, and is characterized by the most affordable price among analogues. The study which included 48 patients demonstrated high efficacy of Sparex administered for 4 weeks in a dosage of 200 mg twice daily for relief of pain, flatulence and stool normalization both in IBS and IBS-related disorders. Good and satisfactory results evaluated by a 3-point scale were achieved in 87.5% of patients. The results allowed to conclude that the medicine, apart from its strong antispasmodic effect, also provided a eukinetic action - normalization of the transit of chyme in the intestine both in constipation and diarrhea. Normalization of stool was observed in 77.2% of patients with both constipation and diarrhea, and in the rest of patients the severity of stool disorders decreased by more than 1 point. In the course of the study, no side effects were observed while taking Sparex.

Blastocystis in Health and Disease: Are We Moving from a Clinical to a Public Health Perspective?

Blastocystis is a genus of common single-celled intestinal parasitic protists with an unsettled role in human health and disease. Being a stable component of intestinal microbiota, once established, the Blastocystis parasite appears more common in healthy individuals than in patients with infectious, functional, or inflammatory bowel disease. Recent data suggest that the parasite is associated with certain gut microbiota profiles and health indices. Convincing data and tools differentiating asymptomatic colonization from infection are yet to be demonstrated. Although the parasite may elicit disease under certain circumstances, the focus on Blastocystis may be shifting from a clinical to a public health perspective.

Functional Bowel Disease.

Functional Bowel Disease.

Comparison of three commercial fecal calprotectin ELISA test kits used in patients with Inflammatory Bowel Disease

Objective: Fecal calprotectin is a noninvasive marker of intestinal inflammation used to distinguish between functional and organic bowel diseases and to evaluate disease activity among patients with Inflammatory Bowel Disease (IBD). The goal of this study was to compare three different ELISA tests measuring calprotectin in their accuracy to detect IBD and to distinguish between IBD patients with active or inactive disease. Material and methods: This study includes in total 148 fecal samples, 96 from patients with a previously confirmed IBD diagnosis and 52 from healthy controls, aged from 25 to 86 and 18 to 67 years, respectively. Disease activity in the patients was established using the following clinical activity indices: the Simple Clinical Colitis Activity Index (SCCAI), the Harvey Bradshaw Index (HBI) and the Modified Pouchitis Disease Activity Index (MPDAI). Three ELISA calprotectin tests (EK-CAL, CALPRO and HK325) were performed on fecal specimens and results compared. Results: The CALPRO calprotectin ELISA test was shown to have the best specificity of 96% compared to the HK325 and the EK-CAL calprotectin ELISA tests with 28% specificity and 74% specificity, respectively. A significant correlation between clinical activity indices and fecal calprotectin was found in patients with ulcerative colitis (p < 0.05***) and in patients with an ileoanal pouch (p < 0.05), but not in patients with Crohn’s disease (p = 0.11). Conclusion: The CALPRO ELISA test performed best in measuring calprotectin in feces.

Adverse Food Reaction and Functional Gastrointestinal Disorders: Role of the Dietetic Approach.

Bloating, abdominal discomfort or pain, disturbed bowel habits are very common symptoms, frequently reported by the patients soon after food ingestion. These symptoms may occur in different clinical conditions, such as functional bowel disorders, food adverse reactions, gluten-related syndromes, which frequently are interrelated. Consequently, in clinical practice, it is necessary to perform a correct diagnosis in order to identify, for the single patient, the most appropriate therapeutic strategy, which may include not only specific drugs, but also, and mainly, life style changes (healthy nutritional behavior and constant physical activity). The aim of this review is to provide to the general physician, according to the available evidence, the most appropriate diagnostic work-ups for recognizing the different clinical scenarios (i.e. food allergy and intolerance, functional bowel diseases, gluten-related syndromes), to identify their clinical interrelationships and to suggest the most appropriate management. In fact, as far as food intolerances are concerned, it is well known that the number of patients who believe that their symptoms are related to food intolerance is increasing and consequently they restrict their diet, possibly causing nutritional deficiencies. Furthermore, there is an increasing use of unconventional diagnostic tests for food intolerance which lack accurate scientific evidence; the application of their results may induce misdiagnosis and unhealthy therapeutic choices. Consequently the recognition of food intolerance has to be performed on the basis of reliable tests within an agreed diagnostic workup.

An Epistatic Interaction between Themis1 and Vav1 Modulates Regulatory T Cell Function and Inflammatory Bowel Disease Development.

The development of inflammatory diseases depends on complex interactions between several genes and various environmental factors. Discovering new genetic risk factors and understanding the mechanisms whereby they influence disease development is of paramount importance. We previously reported that deficiency in Themis1, a new actor of TCR signaling, impairs regulatory T cell (Treg) function and predisposes Brown-Norway (BN) rats to spontaneous inflammatory bowel disease (IBD). In this study, we reveal that the epistasis between Themis1 and Vav1 controls the occurrence of these phenotypes. Indeed, by contrast with BN rats, Themis1 deficiency in Lewis rats neither impairs Treg suppressive functions nor induces pathological manifestations. By using congenic lines on the BN genomic background, we show that the impact of Themis1 deficiency on Treg suppressive functions depends on a 117-kb interval coding for a R63W polymorphism that impacts Vav1 expression and functions. Indeed, the introduction of a 117-kb interval containing the Lewis Vav1-R63 variant restores Treg function and protects Themis1-deficient BN rats from spontaneous IBD development. We further show that Themis1 binds more efficiently to the BN Vav1-W63 variant and is required to stabilize its recruitment to the transmembrane adaptor LAT and to fully promote the activation of Erk kinases. Together, these results highlight the importance of the signaling pathway involving epistasis between Themis1 and Vav1 in the control of Treg suppressive function and susceptibility to IBD development.

Prevalence of celiac disease in Indian patients with irritable bowel syndrome and uninvestigated dyspepsia.

The clinical spectrum of celiac disease (CeD) is wide and its symptoms overlap with those of functional bowel diseases. This study aimed to investigate the relationship among gluten-related disorders, irritable bowel syndrome (IBS) and uninvestigated dyspepsia in Indian patients. Patients with IBS and uninvestigated dyspepsia (using Rome III criteria) were tested for immunoglobulin A (IgA) anti-tissue transglutaminase (anti-tTG) antibody and anti-gliadin antibody (AGA). Those with positive anti-tTG antibody were evaluated for the presence of villous abnormalities. Patients who were only IgA AGA-positive were considered to have gluten sensitivity and those with positive anti-tTG antibody and villous atrophy were considered to have CeD. Of 362 patients with IBS, 22 (6.1%) had positive anti-tTG antibody, among whom 3 (0.8%) had CeD and 19 had potential CeD. Of 358 patients with uninvestigated dyspepsia, 18 (5.0%) were anti-tTG antibody-positive and among them 4 (1.1%) had CeD and 14 had potential CeD. AGA was positive in 104 (28.7%) patients with IBS and 68 (19.0%) with uninvestigated dyspepsia, suggesting the presence of gluten sensitivity. This study highlights the relationship between IBS or dyspepsia and CeD or gluten sensitivity.

Peripheral aetiopathogenic drivers and mediators of Parkinson's disease and co-morbidities: role of gastrointestinal microbiota.

We seek an aetiopathogenic model for the spectrum of Parkinson’s disease (PD), functional bowel disease, depression and cognitive impairment. The adopted concept is that systemic immuno-inflammatory processes mediate neuro-inflammation. The model would be based on phenotype, exposome (including gastrointestinal microbiome), milieu (immuno-inflammatory and metabolome), human genetics and their interactions. It would enable a patient’s position, to be understood in terms of drivers, perpetuators and mediators, and a future position, with and without intervention, predicted. Even the cardinal facets of PD may have different drivers: halting one may allow escape down subordinate pathways. Peptic ulceration is prodromal to PD. In our randomised placebo-controlled trial, hypokinesia improved over the year following biopsy-proven Helicobacter pylori eradication and rigidity worsened. This was independent of any (stable, long t½) antiparkinsonian medication. There are pointers to an autoimmune process: for example, surveillance-confirmed hypokinesia effect was indication specific. During surveillance, successive antimicrobial courses, other than for Helicobacter, were associated with cumulative increase in rigidity. Exhibiting laxatives appeared to stem the overall temporal increase, despite antiparkinsonian medication, in rigidity. Thus, intestinal dysbiosis may be a major source of bystander neuronal damage. There are biological gradients of objective measures of PD facets on circulating inflammatory markers and leucocyte subset counts. Moreover, lactulose hydrogen breath test positivity for small-intestinal bacterial overgrowth (present in two thirds of PD patients) is associated with the same subsets: higher natural killer and total CD4+ counts and lower neutrophils. With greater aetiopathogenic understanding, relatively low cost and on-the-shelf medication could have a major impact. A new generation of animal models, based on the gut microbiome, is envisaged.

A new role for reticulon-4B/NOGO-B in the intestinal epithelial barrier function and inflammatory bowel disease.

Inflammatory bowel disease (IBD) is characterized by an impaired intestinal barrier function. We aimed to investigate the role of reticulon-4B (RTN-4B/NOGO-B), a structural protein of the endoplasmic reticulum, in intestinal barrier function and IBD. We used immunohistochemistry, confocal microscopy, real-time PCR, and Western blotting to study tissue distribution and expression levels of RTN-4B/NOGO-B in control and IBD samples from mouse and humans. We also targeted RTN-4B/NOGO-B using siRNAs in cultured human intestinal epithelial cell (IECs). Epithelial barrier permeability was assessed by transepithelial electrical resistance (TEER) measurement. RTN-4B/NOGO-B is expressed in the intestine mainly by IECs. Confocal microscopy revealed a colocalization of RTN-4B, E-cadherin, and polymerized actin fibers in tissue and cultured IECs. RTN-4B mRNA and protein expression were lower in the colon of IL-10(-/-) compared with wild-type mice. Colocalization of RTN-4B/E-cadherin/actin was reduced in the colon of IL-10(-/-) mice. Analysis of endoscopic biopsies from IBD patients showed a significant reduction of RTN-4B/NOGO-B expression in inflamed mucosa compared with control. Treatment of IECs with H2O2 reduced TEER values and triggered phosphorylation of RTN-4B in serine 107 residues as well as downregulation of RTN-4B expression. Acute RTN-4B/NOGO-B knockdown by siRNAs resulted in a decreased TEER values and reduction of E-cadherin and α-catenin expression and in the amount of F-actin-rich filaments in IECs. Epithelial RTN-4B/NOGO-B was downregulated in human and experimental IBD. RTN-4B participates in the intestinal epithelial barrier function, most likely via its involvement in E-cadherin, α-catenin expression, and actin cytoskeleton organization at sites of cell-to-cell contacts.

Sa1391 Shy Bowel Disorder May Be an Under-Recognized Component of Functional Bowel Disease

Sa1391 Shy Bowel Disorder May Be an Under-Recognized Component of Functional Bowel Disease