Mast cell activation and nutritional disorders in patients with hypermobility.

PURPOSE OF REVIEW: Individuals with joint hypermobility disorders are increasingly referred to gastroenterology services for support with the investigation and management of gastrointestinal complaints. Individuals can present with a myriad of complex coexisting diagnoses, the inter-relationship of which is unclear. This review discusses the proposed association between hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorder (HSD) with disorders of mast cell activation and provides an overview of gastrointestinal symptoms and nutritional outcomes in this patient cohort. RECENT FINDINGS: It is unclear whether a true association between hEDS/HSD and mast cell activation disorders exists. There is a high prevalence of nonspecific gastrointestinal symptoms in individuals with hEDS/HSD and patients may be at risk of macro-nutrient and micro-nutrient deficiencies, although the current evidence base is limited. SUMMARY: We advocate a pragmatic approach to the investigation and management of gastrointestinal symptoms in patients with hEDS/HSD. This centres on excluding organic pathology, discussing the overlap with disorders of gut-brain interactions, trialling evidence-based therapies targeting individual symptoms, and supporting nutritional deficiencies where present via the least invasive approach. Engagement with a broad multidisciplinary team is also important to support the holistic needs of this patient cohort.

British Society of Gastroenterology guidelines on the management of functional dyspepsia.

Functional dyspepsia (FD) is a common disorder of gut-brain interaction, affecting approximately 7% of individuals in the community, with most patients managed in primary care. The last British Society of Gastroenterology (BSG) guideline for the management of dyspepsia was published in 1996. In the interim, substantial advances have been made in understanding the complex pathophysiology of FD, and there has been a considerable amount of new evidence published concerning its diagnosis and classification, with the advent of the Rome IV criteria, and management. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based diagnosis and treatment of patients. The approach to investigating the patient presenting with dyspepsia is discussed, and efficacy of drugs in FD summarised based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of pairwise and network meta-analyses. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system. These provide both the strength of the recommendations and the overall quality of evidence. Finally, in this guideline, we consider novel treatments that are in development, as well as highlighting areas of unmet need and priorities for future research.

Efficacy and Acceptability of Dietary Therapies in Non-Constipated Irritable Bowel Syndrome: A Randomized Trial of Traditional Dietary Advice, the Low FODMAP Diet, and the Gluten-Free Diet.

BACKGROUND & AIMS: Various diets are proposed as first-line therapies for non-constipated irritable bowel syndrome (IBS) despite insufficient or low-quality evidence. We performed a randomized trial comparing traditional dietary advice (TDA) against the low FODMAP diet (LFD) and gluten-free diet (GFD). METHODS: Patients with Rome IV-defined non-constipated IBS were randomized to TDA, LFD, or GFD (the latter allowing for minute gluten cross-contamination). The primary end point was clinical response after 4 weeks of dietary intervention, as defined by ≥50-point reduction in IBS symptom severity score (IBS-SSS). Secondary end points included (1) changes in individual IBS-SSS items within clinical responders, (2) acceptability and food-related quality of life with dietary therapy, (3) changes in nutritional intake, (4) alterations in stool dysbiosis index, and (5) baseline factors associated with clinical response. RESULTS: The primary end point of ≥50-point reduction in IBS-SSS was met by 42% (n = 14/33) undertaking TDA, 55% (n = 18/33) for LFD, and 58% (n = 19/33) for GFD (P = .43). Responders had similar improvements in IBS-SSS items regardless of their allocated diet. Individuals found TDA cheaper (P < .01), less time-consuming to shop (P < .01), and easier to follow when eating out (P = .03) than the GFD and LFD. TDA was also easier to incorporate into daily life than the LFD (P = .02). Overall reductions in micronutrient and macronutrient intake did not significantly differ across the diets. However, the LFD group had the greatest reduction in total FODMAP content (27.7 g/day before intervention to 7.6 g/day at week 4) compared with the GFD (27.4 g/day to 22.4 g/day) and TDA (24.9 g/day to 15.2 g/day) (P < .01). Alterations in stool dysbiosis index were similar across the diets, with 22%-29% showing reduced dysbiosis, 35%-39% no change, and 35%-40% increased dysbiosis (P = .99). Baseline clinical characteristics and stool dysbiosis index did not predict response to dietary therapy. CONCLUSIONS: TDA, LFD, and GFD are effective approaches in non-constipated IBS, but TDA is the most patient-friendly in terms of cost and convenience. We recommend TDA as the first-choice dietary therapy in non-constipated IBS, with LFD and GFD reserved according to specific patient preferences and specialist dietetic input. CLINICALTRIALS: gov: NCT04072991.

Diagnostic Yield of Colonoscopy in Patients With Symptoms Compatible With Rome IV Functional Bowel Disorders.

BACKGROUND & AIMS: There is little data on the diagnostic yield of colonoscopy in patients with symptoms compatible with functional bowel disorders (FBDs). Previous studies have only focused on diagnostic outcomes of colonoscopy in those with suspected irritable bowel syndrome using historic Rome I-III criteria, whilst having partially assessed for alarm features and shown markedly conflicting results. There is also no colonoscopy outcome data for other FBDs, such as functional constipation or functional diarrhea. Using the contemporaneous Rome IV criteria we determined the diagnostic yield of colonoscopy in patients with symptoms compatible with a FBD, stratified diligently according to the presence or absence of alarm features. METHODS: Basic demographics, alarm features, and bowel symptoms using the Rome IV diagnostic questionnaire were collected prospectively from adults attending out-patient colonoscopy in 2019. Endoscopists were blinded to the questionnaire data. Organic disease was defined as the presence of inflammatory bowel disease, colorectal cancer, or microscopic colitis. RESULTS: 646 patients fulfilled symptom-based criteria for the following Rome IV FBDs: IBS (56%), functional diarrhea (27%) and functional constipation (17%). Almost all had alarm features (98%). The combined prevalence of organic disease was 12%, being lowest for functional constipation and IBS-constipation (∼6% each), followed by IBS-mixed (∼9%), and highest amongst functional diarrhea and IBS-diarrhea (∼17% each); p = .005. The increased prevalence of organic disease in diarrheal versus constipation disorders was accounted for by microscopic colitis (5.7% vs. 0%, p < .001) but not inflammatory bowel disease (7.2% vs. 4.0%, p = .2) or colorectal cancer (4.2% vs. 2.3%, p = .2). However, 1-in-4 chronic diarrhea patients - conceivably at risk for microscopic colitis - did not have colonic biopsies taken. Finally, only 11 of 646 (2%) patients were without alarm features, in whom colonoscopy was normal. CONCLUSIONS: Most patients with symptoms of FBDs who are referred for colonoscopy have alarm features. The presence of organic disease is significantly higher in diarrheal versus constipation disorders, with microscopic colitis largely accounting for the difference whilst also being a missed diagnostic opportunity. In those patients without alarm features, the diagnostic yield of colonoscopy was nil.

Functional Gastrointestinal Disorders and Associated Health Impairment in Individuals with Celiac Disease.

BACKGROUND & AIMS: Individuals with celiac disease (CD) can experience persisting gastrointestinal symptoms despite adhering to a gluten-free diet (GFD). This may be due to functional gastrointestinal disorders (FGIDs), although there is little data on its prevalence and associated factors. METHODS: An online health questionnaire was completed by adult members of Celiac UK in October 2018. The survey included validated questions on Rome IV FGIDs, nongastrointestinal somatic symptoms, anxiety, depression, quality of life, health care use, GFD duration, and its adherence using the celiac dietary adherence test score (with a value ≤ 13 indicating optimal adherence). The prevalence of FGIDs and associated health impairment in the celiac cohort was compared against an age- and sex-matched population-based control group. RESULTS: Of the 863 individuals with CD (73% female; mean age, 61 years), all were taking a GFD for at least 1 year, with 96% declaring that they have been on the diet for 2 or more years (2-4 years, 20%; ≥5 years, 76%). The adherence to a GFD was deemed optimal in 61% (n = 523), with the remaining 39% (n = 340) nonadherent. Those adhering to a GFD fulfilled criteria for a FGID in approximately one-half of cases, although this was significantly lower than nonadherent subjects (51% vs 75%; odds ratio [OR], 2.0; P < .001). However, the prevalence of FGIDs in GFD-adherent subjects was significantly higher than in matched population-based controls (35%; OR, 2.0; P < .001). This was accounted for by functional bowel (46% vs 31%; OR, 1.9; P < .0001) and anorectal disorders (14.5% vs 9.3%; OR, 1.7; P = .02) but not functional esophageal (7.6% vs 6.1%; P = .36) or gastroduodenal disorders (8.7% vs 7.4%; P = .47). Finally, GFD-adherent subjects with FGIDs were significantly more likely than their counterparts without FGIDs to have abnormal levels of anxiety (5% vs 2%; OR, 2.8; P = .04), depression (7% vs 2%; OR, 3.6; P = .01), somatization (31% vs 8%; OR, 5.1; P < .0001), and reduced quality of life (P < .0001). CONCLUSION: One in 2 people with CD, despite having been on a GFD for a number of years and demonstrating optimal adherence, have ongoing symptoms compatible with a Rome IV FGID. This is 2-fold the odds of FGIDs seen in age- and sex-matched controls. The presence of FGIDs is associated with significant health impairment, including psychological comorbidity. Addressing disorders of gut-brain interaction might improve outcomes in this specific group of patients.

Greater Overlap of Rome IV Disorders of Gut-Brain Interactions Leads to Increased Disease Severity and Poorer Quality of Life.

BACKGROUND AND AIMS: Conditions such as irritable bowel syndrome (IBS), functional dyspepsia, and functional constipation are among the prevalent gastrointestinal (GI) disorders classified as disorders of gut-brain interaction (DGBI), which can adversely affect the lives of sufferers. This study aimed to assess the degree and consequences of overlapping DGBI in a large population-based global scale. METHODS: Internet survey data from 54,127 adults (49.1% women) in 26 countries were analyzed by 4 GI anatomic regions (esophageal, gastroduodenal, bowel, and anorectal). The number of DGBI-affected GI regions was assessed, including associations with sex, age, disease severity, quality of life, psychosocial variables, and health care utilization. RESULTS: A total of 40.3% of surveyed individuals met Rome IV criteria for a DGBI. The percentages with 1-4 DGBI-affected GI regions were 68.3%, 22.3%, 7.1%, and 2.3%, respectively. The IBS symptom severity score increased significantly from 1 (207.6) to 4 (291.6) regions, as did non-GI symptom reporting (somatization), anxiety and depression, concerns and embarrassment about bowel function, doctor visits, medications, and abdominal surgeries (all P < .0001). Quality of life decreased with increasing number of DGBI regions (P < .0001). In a logistic mixed model, non-GI symptoms (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.08-1.10), being very vs not concerned (OR, 2.55; 95% CI, 2.27-2.90), being very vs not embarrassed about bowel function (OR, 1.20; 95% CI, 1.08-1.33), and mean number of doctor visits (OR, 1.23; 95% CI, 1.115-1.32) were most strongly associated with number of DGBI regions. CONCLUSIONS: DGBI in multiple anatomic GI regions is associated with increased psychological comorbidity, health care utilization, and IBS severity. Physician awareness of overlap could improve quality of care, prevent unnecessary interventions, and yield more positive health outcomes.

Fecal Immunochemical Testing in Patients With Low-Risk Symptoms of Colorectal Cancer: A Diagnostic Accuracy Study.

BACKGROUND: The fecal immunochemical test (FIT) is recommended for triaging primary care patients in England with low-risk symptoms of colorectal cancer (CRC). The evidence underpinning recommendations by the National Institute for Health and Care Excellence had limitations, with a paucity of primary care evidence. This study examines the diagnostic accuracy of FIT in a defined low-risk symptom primary care population. PATIENTS AND METHODS: Consecutive symptomatic adult patients referred for a FIT between October and December 2019 were included. Patients were derived from 225 primary care practices in England. Serious colorectal diseases (CRC, high-risk polyps, and inflammatory bowel disease [IBD]) were identified through patient follow-up over 18 months, using both primary and secondary healthcare records. Performance characteristics of FIT are reported according to differing thresholds, including the currently recommended threshold of ≥10 µg hemoglobin per gram of feces (µg/g). RESULTS: A total of 3,506 patients were included in the final analysis. Of these, 708 had a positive FIT result (≥10 µg/g). The prevalence of CRC was 1.3%. FIT positivity declined from 20.2% to 5.8% and 4.5% at cutoffs of 10, 80, and 120 µg/g, respectively. The sensitivity of FIT at ≥10 µg/g to detect CRC was 91.1% (95% CI, 77.9%-97.1%); its specificity was 80.7% (95% CI, 79.3%-82.0%); the positive predictive value (PPV) was 5.8% (95% CI, 4.2%-7.8%); and the negative predictive value (NPV) was 99.9% (95% CI, 99.6%-99.95%). The area under the receiver operating characteristic curve was 0.93 (0.91-0.96). PPV and specificity increased, whereas sensitivity and NPV decreased when serious colorectal diseases (CRC, high-risk polyps, and IBD) were combined. Age, sex, socioeconomic deprivation, and anemia did not significantly influence FIT sensitivity on subgroup analysis. CONCLUSIONS: Utilization of FIT at a threshold ≥10 µg/g can safely triage patients with low-risk symptoms in primary care, with negative results effectively ruling out CRC.

British Society of Gastroenterology guidelines on the management of irritable bowel syndrome.

Irritable bowel syndrome (IBS) remains one of the most common gastrointestinal disorders seen by clinicians in both primary and secondary care. Since publication of the last British Society of Gastroenterology (BSG) guideline in 2007, substantial advances have been made in understanding its complex pathophysiology, resulting in its re-classification as a disorder of gut-brain interaction, rather than a functional gastrointestinal disorder. Moreover, there has been a considerable amount of new evidence published concerning the diagnosis, investigation and management of IBS. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based management of patients. One of the strengths of this guideline is that the recommendations for treatment are based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of trial-based and network meta-analyses assessing the efficacy of dietary, pharmacological and psychological therapies in treating IBS. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system, summarising both the strength of the recommendations and the overall quality of evidence. Finally, this guideline identifies novel treatments that are in development, as well as highlighting areas of unmet need for future research.

Rome IV Functional Gastrointestinal Disorders and Health Impairment in Subjects With Hypermobility Spectrum Disorders or Hypermobile Ehlers-Danlos Syndrome.

BACKGROUND & AIMS: Individuals with hypermobility spectrum disorder or hypermobile Ehlers-Danlos Syndrome (HSD/hEDS) are increasingly encountered by gastroenterologists and pose complex clinical challenges. Uncontrolled studies have found functional gastrointestinal disorders (FGIDs) to be common in patients with HSD/hEDS. Some patients have somatic symptoms (medically unexplained symptoms) that might affect FGIDs. We performed a case-control study to determine the prevalence of and factors associated with Rome IV FGIDs in subjects with HSD/hEDS compared with age- and sex- matched population-based controls. METHODS: An online general health survey was completed by 603 individuals with HSD/hEDS in October 2018 (cases) and 603 matched individuals from the population of the United Kingdom (controls) in 2015. The mean participant age was 39 yrs, and 96% were women. The survey included questions about Rome IV FGIDs, non-GI and non-musculoskeletal somatic symptoms (maximum number, 10), quality of life, medical history and healthcare use. The prevalence of FGIDs was compared between cases and controls, with subsequent logistic regression models - adjusting for the number of somatic symptoms - used to determine the associations for FGIDs in HSD/hEDS compared with controls. RESULTS: Nearly all subjects (98%) with HSD/hEDS fulfilled symptom-based criteria for 1 or more Rome IV FGIDs, compared with 47% of controls (P < .0001). The gastrointestinal regions most commonly affected by FGIDs in individuals with HSD/hEDS and control subjects were the bowel (90% vs 40% of controls), gastroduodenal (70% vs 13% of controls), esophageal (56% vs 6% of controls), and anorectal (53% vs 9% of controls); P < .0001. A higher proportion of subjects with HSD/hEDS had FGIDs in 2 or more regions (84% vs 15% of controls; P < .0001). Subjects with HSD/hEDS also reported a significantly higher number of non-GI and non-musculoskeletal somatic symptoms (7.1 vs 3.3 in controls), lower quality of life, and greater healthcare use, including abdominal surgeries and medication use (for example, 84% used analgesics compared with 29% of controls). Almost 40% of subjects with HSD/hEDS reported a diagnosis of chronic fatigue syndrome and/or fibromyalgia. Following adjustments for somatic symptoms, the association for FGIDs in subjects with HSD/hEDS was reduced by as much as 4-fold and in some instances was eliminated. CONCLUSIONS: In a large case-control study of persons with HSD/hEDS, almost all of the cases met criteria for Rome IV FGIDs, incurred considerable health impairment, and had high healthcare use. Patients with HSD/hEDS frequently have somatic symptoms that should be treated to reduce the high burden of gastrointestinal illness in this population.

Physicochemical, antidiarrheal and antidiabetic potential of super food (Moringa oleifera Lam.).

There is a long history of natural products for the treatment of infections and diseases. The objective of present study was to investigate the organoleptic, microscopic, physico-chemical, phytochemical, antidiarrheal and antidiabetic potential of leaf, flowering bud and stem bark of Moringa oleifera L. Macroscopic, microscopic, physico-chemical parameters and phytochemical screening were carried out. Diarrhea was induced with castor oil (10ml/kg), verapamil (3, 10 and 30mg/kg) were used as standard antidiarrheal drug and extract of Moringa oleifera at (100, 300 and 1000mg/kg) was used for treatment. Alpha glucosidase inhibitory assay was carried out by using acarbose (0.5mM) and extracts (5.0 mg/Ml). Diabetes was induced by alloxan (150mg/kg), while glibenclamide (10mg/kg) was used as standard drug, and extracts (at the doses of 500mg/kg) were used to determine the antidiabetic activity. Results showed the presence of primary and secondary metabolites, treatment at the dose of 1.0g/kg of leaf, flowering bud and stem bark showed 94 ±2.527, 85.42±5.460 and 84.58±6.138% protection respectively whereas verapamil (10mg/kg) showed 94.84±3.27% protection. Alpha glucosidase inhibition of stem bark (0.5mg/ml) was 95.43±1.47 and flowering bud 94.78±1.25 whereas acarbose (5mM) inhibition was 92.23±0.14%. Stem bark and flowering bud extract (500mg/kg) decreases the blood glucose level from 388.5±35.83 to 226.3±47.10 and 322.5±48.35 to 173.8±29.5 respectively whereas glibenclamide (10 mg/kg) decreases the blood glucose level from 320.7±22.9 to 146.3±17.7 and increases the body weight of the experimental animal. It was concluded from the results that stem bark has strong antidiabetic potential while leaves of the plant have promising antidiarrheal effect.

Use of small-bowel capsule endoscopy in cases of equivocal celiac disease.

BACKGROUND AND AIMS: Seronegative villous atrophy (SNVA), raised intraepithelial lymphocytes (IELs), and crypt hyperplasia on duodenal histology can be secondary to celiac disease (CD) or other causes such as medications or infections. Our aims were to assess the role of small-bowel capsule endoscopy (SBCE) in these patients and to ascertain whether findings on SBCE at diagnosis can predict disease outcome. METHODS: Patients (n = 177) with SNVA, IELs, ± crypt hyperplasia on duodenal histology were studied. These patients all had an equivocal diagnosis of CD. RESULTS: Overall, 56 patients (31.6%) had a positive SBCE. Thirty-three patients (58.9%) had disease affecting the proximal third of the small bowel (SB). The diagnostic yield of SBCE was 40.0% (22 patients), 51.4% (18 patients), 27.0% (10 patients), and 14.0% (7 patients) in patients with an unknown cause for SNVA (SNVA-UO), patients with SNVA who responded to a gluten-free diet (SNVA-CD), patients with a known cause for SNVA, and patients with railed IELs ± crypt hyperplasia, respectively. In SNVA-UO, SBCE at diagnosis was more likely to be positive in patients with persistent SNVA (10, 90.9%) and persistent SNVA with lymphoproliferative features (4, 80.4%) than patients with spontaneous resolution of SNVA (8, 20.5%) (P = .0001). All patients in the SNVA-CD group who eventually developed adverse events had a positive SBCE (P = .022). They also had more extensive SB disease than those without adverse events (50% vs 1% P = .002). More extensive SB disease on SBCE correlated with a higher SNVA-related mortality in patients with SNVA-UO and SNVA-CD (P = .019). Severity of histology did not correlate with mortality (P = .793). CONCLUSIONS: A positive SBCE at diagnosis predicts a worse outcome. More importantly, more extensive disease in these patients is associated with poor survival. Targeting patients with extensive disease at diagnosis with more aggressive therapy can help to improve prognosis.

Epidemiology, Clinical Characteristics, and Associations for Rome IV Functional Nausea and Vomiting Disorders in Adults.

BACKGROUND & AIMS: Functional nausea and vomiting disorders (FNVDs) are classified as chronic nausea and vomiting syndrome (CNVS) or cyclic vomiting syndrome (CVS)-CVS includes cannabinoid hyperemesis syndrome. We investigated the population prevalence of FNVDs, their characteristics, and associated factors. METHODS: In the year 2015, an Internet cross-sectional health survey was completed by 5931 adults in the general populations of 3 English-speaking countries; 2100 participants were in the United States, Canada, or the United Kingdom. Quota-based sampling was used to generate demographically balanced and population-representative samples. The survey collected data on demographics, health care visits, medications, somatic symptom severity, quality of life, and symptom-based diagnostic criteria for Rome IV FNVDs as well as for irritable bowel syndrome and functional dyspepsia. Subsequent comparisons were made between Rome IV FNVD subjects and individuals without FNVDs (controls). RESULTS: Overall, 2.2% of the population (n = 131) fulfilled symptom-based diagnostic criteria for Rome IV FNVDs: the United States (3%) had a greater prevalence than Canada (1.9%) or the United Kingdom (1.8%) (P = .02). The prevalence of CNVS was similar among the countries, ranging from 0.8% to 1.2%. However, the prevalence of CVS was higher in the United States (2%) than in Canada (0.7%) or the United Kingdom (1%) (P = .03). The proportion of subjects with CVS taking cannabis did not differ significantly among countries (P = .31), although the 7 cases of cannabinoid hyperemesis syndrome were in the United States. A significantly higher proportion of subjects with CVS reported a compulsive need for hot water bathing to alleviate emetic symptoms than subjects with CNVS (44% vs 19%; P = .03); this behavior was independent of cannabis but augmented by its use. Subjects with FNVDs had significantly greater health impairment and health care utilization than controls. On multivariate analysis, independent factors associated with FNVDs were younger age, increasing somatic symptom severity, lower quality of life, presence of irritable bowel syndrome, and functional dyspepsia. However, on subgroup analysis, somatic symptom severity was associated with CVS but not CNVS, whereas poor quality of life was associated with CNVS but not CVS. CONCLUSIONS: Based on a cross-sectional health survey of adults in the general populations of 3 English-speaking countries, approximately 2% of subjects meet symptom-based criteria for Rome IV FNVDs and have considerable health impairments. Hot water bathing to alleviate emetic symptoms is reported for all FNVDs, and is perpetuated by cannabis use.

The Global Phenomenon of Self-Reported Wheat Sensitivity.

Celiac disease affects about 1% of the population and is treated with a gluten-free diet. However, the last decade has seen a huge rise in individuals self-reporting wheat sensitivity, and consuming a gluten-free diet, despite not having a doctor-diagnosis of celiac disease. A recent flurry of observational studies from across the globe suggests that approximately 10% of the population is self-reporting wheat sensitivity. They describe a constellation of intestinal and extra-intestinal symptoms attributed to ingestion of gluten-based products. This phenomenon poses a significant challenge to clinicians with regards to adequately excluding celiac disease, identifying the culprit agent, understanding the pathophysiology, and providing safe aftercare.

The Prevalence and Impact of Overlapping Rome IV-Diagnosed Functional Gastrointestinal Disorders on Somatization, Quality of Life, and Healthcare Utilization: A Cross-Sectional General Population Study in Three Countries.

OBJECTIVES: The population prevalence of Rome IV-diagnosed functional gastrointestinal disorders (FGIDs) and their cumulative effect on health impairment is unknown. METHODS: An internet-based cross-sectional health survey was completed by 5,931 of 6,300 general population adults from three English-speaking countries (2100 each from USA, Canada, and UK). Quota-based sampling was used to generate demographically balanced and population representative samples with regards to age, sex, and education level. The survey enquired for demographics, medication, surgical history, somatization, quality of life (QOL), doctor-diagnosed organic GI disease, and criteria for the Rome IV FGIDs. Comparisons were made between those with Rome IV-diagnosed FGIDs against non-GI (healthy) and organic GI disease controls. RESULTS: The number of subjects having symptoms compatible with a FGID was 2,083 (35%) compared with 3,421 (57.7%) non-GI and 427 (7.2%) organic GI disease controls. The most frequently met diagnostic criteria for FGIDs was bowel disorders (n=1,665, 28.1%), followed by gastroduodenal (n=627, 10.6%), anorectal (n=440, 7.4%), esophageal (n=414, 7%), and gallbladder disorders (n=10, 0.2%). On average, the 2,083 individuals who met FGID criteria qualified for 1.5 FGID diagnoses, and 742 of them (36%) qualified for FGID diagnoses in more than one anatomic region. The presence of FGIDs in multiple regions was associated with increasing somatization, worse mental/physical QOL, more medical therapies, and a higher prevalence of abdominal surgeries; all P<0.001. Notably, individuals with FGIDs in multiple regions had greater somatization and worse QOL than organic GI disease controls. CONCLUSIONS: Roughly a third of the general adult population fulfils diagnostic criteria for a Rome IV FGID. In a third of this subset multiple GI regions are involved and this overlap is associated with increased health impairment.

How the Change in IBS Criteria From Rome III to Rome IV Impacts on Clinical Characteristics and Key Pathophysiological Factors.

OBJECTIVES: The diagnostic criteria for irritable bowel syndrome (IBS) have recently been updated from Rome III to Rome IV. Whereas in Rome III a diagnosis of IBS entailed chronic abdominal pain or discomfort at least 3 days per month, in Rome IV the term discomfort has been removed and the frequency of abdominal pain increased to at least 1 day per week. We examined how this change in IBS criteria impacts on clinical characteristics and pathophysiological factors. METHODS: A total of 542 Swedish subjects with Rome III IBS completed a baseline questionnaire enquiring for the number of abdominal pain days in the last 10 days; this was subsequently used as a surrogate marker to identify Rome IV IBS, in that (a) those with 0 or 1 day of pain were classed as Rome IV-negative, and (b) those with ≥2 days of pain were classed as Rome IV-positive. Comparisons were made between Rome IV-positive and -negative IBS groups for demographics, IBS subtype, gastrointestinal and psychological symptoms, somatisation, fatigue, disease-specific quality of life, rectal sensitivity, and oro-anal transit time. RESULTS: Overall, 85% of Rome III IBS patients fulfilled the Rome IV criteria for IBS, but 15% did not. Rome IV-positive subjects were significantly more likely to be female, have poorer quality of life, greater pain severity, bloating, somatisation, fatigue, and rectal sensitivity than Rome IV-negative subjects. There were no differences in severity of anxiety or depression, IBS subtypes, bowel habit dissatisfaction, or oro-anal transit time. Finally, increasing number of pain days correlated positively with symptoms and visceral hypersensitivity. CONCLUSIONS: Most Rome III-positive IBS patients seeking healthcare fulfil the Rome IV IBS criteria. They constitute a more severe group than those who lose their IBS diagnosis.

The clinical and phenotypical assessment of seronegative villous atrophy; a prospective UK centre experience evaluating 200 adult cases over a 15-year period (2000-2015).

BACKGROUND: Seronegative villous atrophy (SNVA) is commonly attributed to coeliac disease (CD). However, there are other causes of SNVA. More recently angiotensin-2-receptor-blockers (A2RBs) have been reported as an association but data on SNVA have been limited to centres evaluating complex case referrals and not SNVA in general. OBJECTIVES: To provide clinical outcomes and associations in a large prospective study overseeing all newcomers with SNVA. DESIGN: Over a 15-year period (2000-2015) we evaluated 200 adult patients with SNVA at a UK centre. A diagnosis of either seronegative CD (SNCD) or seronegative non-CD (SN-non-CD) was reached. Baseline comparisons were made between the groups, with 343 seropositive CD subjects serving as controls. RESULTS: Of the 200 SNVA cases, SNCD represented 31% (n=62) and SN-non-CD 69% (n=138). The human leucocyte antigen (HLA)-DQ2 and/or DQ8 genotype was present in 61%, with a 51% positive predictive value for SNCD. The breakdown of identifiable causes in the SN-non-CD group comprised infections (27%, n=54), inflammatory/immune-mediated disorders (17.5%, n=35) and drugs (6.5%, n=13; two cases related to A2RBs). However, no cause was found in 18% (n=36) and of these 72% (n=26/36) spontaneously normalised duodenal histology while consuming a gluten-enriched diet. Following multivariable logistic regression analysis an independent factor associated with SN-non-CD was non-white ethnicity (OR 10.8, 95% CI 2.2 to 52.8); in fact, 66% of non-whites had GI infections. On immunohistochemistry all groups stained positive for CD8-T-cytotoxic intraepithelial lymphocytes. However, additional CD4-T helper intraepithelial lymphocytes were occasionally seen in SN-non-CD mimicking the changes associated with refractory CD. CONCLUSIONS: Most patients with SNVA do not have CD, in particular those who are not white. Furthermore, a subgroup with no obvious aetiology will show spontaneous histological resolution while consuming gluten. These findings suggest caution in empirically prescribing a gluten-free diet without investigation.