Quality of Life and Bidirectional Gut-Brain Interactions in Irritable Bowel Syndrome From Adolescence to Adulthood.

BACKGROUNDS AND AIMS: Reports on cross-sectional and longitudinal associations between health-related quality of life (HRQoL), psychological distress, and irritable bowel syndrome (IBS) in the adolescent and young adult general population are few. We aimed to describe cross-sectional associations between HRQoL and IBS in adolescence and young adulthood, and examine bidirectional gut-brain interactions in the transition from childhood to adulthood. METHODS: We included 3391 subjects from a prospective birth cohort study, with data on IBS at 16 years of age and 24 years of age. IBS was assessed using the pediatric Rome III (16 years of age) and the adult Rome IV (24 years of age) diagnostic questionnaires. HRQoL and psychological distress were assessed through EQ-5D. Sex-adjusted logistic regression models were used to examine associations between overall HRQoL/psychological distress at 16 years of age and new-onset IBS at 24 years of age (brain-gut) and between IBS at 16 years of age and new-onset psychological distress at 24 years of age (gut-brain). RESULTS: In subjects with vs without IBS at 16 and 24 years of age, overall HRQoL (EQ visual analog scale, EQ-5D index value) was lower, and it was more common reporting problems in 4 of 5 EQ-5D dimensions (all P < .05). EQ-5D index value at 16 years of age was inversely associated (odds ratio [OR], 0.1, 95% confidence interval [CI], 0.01-0.6), and psychological distress at 16 years of age was positively associated (OR, 1.6; 95% CI, 1.2-2.3), with new-onset IBS at 24 years of age. Having any abdominal pain-related disorder of gut-brain interaction at 16 years of age was associated with new-onset psychological distress at 24 years of age (OR, 1.7; 95% CI, 1.2-2.5). CONCLUSIONS: Adolescents and young adults with IBS in the general population have impaired HRQoL. Bidirectional gut-brain interactions are relevant for symptom generation in abdominal pain-related disorders of gut-brain interaction, and for HRQoL impairment and psychological distress in the transition from childhood to adulthood.

Factor Analysis of the Rome IV Criteria for Major Disorders of Gut-Brain Interaction (DGBI) Globally and Across Geographical, Sex, and Age Groups.

BACKGROUND & AIMS: The Rome criteria are widely accepted for diagnosing disorders of gut-brain interaction, but their global applicability has been debated. This study aimed to evaluate the validity of the Rome IV criteria by factor analysis globally, across geographical regions, by sex, and by age groups. METHODS: Data were collected in 26 countries using the Rome IV questionnaire. Forty-nine ordinal variables were used in exploratory factor analysis (EFA) to identify clusters of inter-correlated variables (factors) within the data set. Confirmatory factor analysis with predefined factors of the disorders of gut-brain interaction was compared with the factors in the EFA. Analyses were performed globally, for each geographical region (North and Latin America, Western and Eastern Europe, Middle East, Asia), sex, and age groups (18-34, 35-49, 50-64, ≥65). RESULTS: A total of 54,127 people were included. The EFA identified 10 factors accounting for 57% of the variance: irritable bowel syndrome, constipation, diarrhea, upper gastrointestinal symptoms, globus, regurgitation/retching, chest pain, nausea/vomiting, and 2 right upper quadrant pain factors. Most factors had close correspondence to a Rome IV criteria diagnosis, but notably, functional dysphagia and heartburn symptoms were often included in the same factor and/or in upper gastrointestinal symptoms. Most factors were consistent across geographical regions, sex, and age groups, and compatible to the global results. All prespecified factors in the confirmatory analysis had a loading ≥0.4, indicating validity of the Rome IV criteria. CONCLUSIONS: The results indicate that the Rome IV criteria for irritable bowel syndrome, functional dyspepsia, functional constipation, globus, and biliary pain are globally valid and represent universal diagnostic entities that are similar across sex and age groups.

Association Between Celiac Disease and Irritable Bowel Syndrome: A Nationwide Cohort Study.

BACKGROUND & AIMS: The aim of this study was to determine the risk of irritable bowel syndrome (IBS) diagnosis in patients with celiac disease (CD) compared with general population comparators. METHODS: Using Swedish histopathology and register-based data, we identified 27,262 patients with CD diagnosed in 2002-2017 and 132,922 age- and sex-matched general population comparators. Diagnoses of IBS were obtained from nationwide inpatient and non-primary outpatient records. Cox regression estimated hazard ratios (aHRs) for IBS adjusted for education level and Charlson Comorbidity Index. To reduce potential surveillance bias our analyses considered incident IBS diagnosis ≥1 year after CD diagnosis. Using conditional logistic regression, secondary analyses were calculated to estimate odds ratios (ORs) for IBS diagnosis ≥1 year before CD diagnosis. RESULTS: During an average of 11.1 years of follow-up, 732 celiac patients (2.7%) were diagnosed with IBS vs 1131 matched general population comparators (0.9%). Overall (≥1-year of follow-up), the aHR for IBS was 3.11 (95% confidence interval [CI], 2.83-3.42), with aHR of 2.00 (95% CI, 1.63-2.45) after ≥10 years of follow-up. Compared with siblings (n = 32,010), celiac patients (n = 19,211) had ≥2-fold risk of later IBS (aHR, 2.42; 95% CI, 2.08-2.82). Compared with celiac patients with mucosal healing, those with persistent villus atrophy on follow-up biopsy were less likely to be diagnosed with IBS (aHR, 0.66; 95% CI, 0.46-0.95). CD was also associated with having an earlier IBS diagnosis (OR, 3.62; 95% CI, 3.03-4.34). CONCLUSIONS: In patients with CD, the risk of IBS is increased long before and after diagnosis. Clinicians should be aware of these long-term associations and their implications on patient management.

Global Prevalence of Psychological Distress and Comorbidity With Disorders of Gut-Brain Interactions.

INTRODUCTION: This study focused on defining the global prevalence of clinically relevant levels of psychological distress and somatic symptoms and the prevalence of coexistence between these symptoms and disorders of gut-brain interaction (DGBI). We also analyzed how clinically relevant psychological distress and somatic symptoms and coexistent DGBI are associated with health-related outcomes. METHODS: We included a representative sample of 54,127 adult participants (49.1% women; mean age of 44.3 years) from 26 countries worldwide. Participants completed an Internet survey (the Rome Foundation Global Epidemiology Study) with validated self-report questionnaires. RESULTS: Clinically relevant psychological distress and/or somatic symptom severity was reported by 37.5% of the sample. These participants had 4.45 times higher odds to have at least one DGBI than individuals without psychological distress and/or somatic symptoms. Compared with participants with psychological distress and/or somatic symptoms with vs without DGBI, participants with a DGBI reported increased healthcare and medication utilization (with OR from 1.6 to 2.8). Coexistent DGBI in participants with psychological distress and/or somatic symptoms was the variable most strongly associated with reduced mental (ß = -0.77; confidence interval [-0.86 to -0.68]) and physical (ß = -1.17; confidence interval [-1.24 to -1.10]) quality of life. DISCUSSION: This global study shows that psychological distress, somatic symptoms, and DGBI are very common and frequently overlap. The coexistence between psychological distress/somatic symptoms and DGBI seems to be especially detrimental to quality of life and healthcare utilization. Individuals with psychological distress/somatic symptoms and DGBI coexistence seem to be a group vulnerable to psychosocial problems that should be studied further and would likely benefit from psychological/psychiatric interventions.

Global Prevalence and Impact of Rumination Syndrome.

BACKGROUND & AIMS: Rumination syndrome is a Disorder of Gut-Brain Interaction (DGBI) of unknown etiology. We aimed to assess its global prevalence and potential associations with other medical conditions. METHODS: Data were collected via the Internet in 26 countries. Subjects were evenly distributed by country, sex, and age groups and were invited for a "health survey" using the Rome IV diagnostic questionnaire and a supplementary questionnaire addressing factors potentially associated with DGBI. RESULTS: In all, 54,127 subjects completed the survey (51% male; mean age, 44.3 years). The overall prevalence of rumination syndrome was 3.1% (95% confidence interval [CI], 3.0-3.3%). It was highest in Brazil (5.5% CI, 4.5-6.5) and lowest in Singapore (1.7% CI, 1.1-2.2). The mean age of people with rumination syndrome was 44.5 years (standard deviation, 15.6) and it was more common in females (54.5% vs 45.5%). Factors independently associated with rumination syndrome were depression (odds ratio [OR], 1.46), anxiety (OR, 1.8), body mass index (OR, 1.04), and female sex (OR, 1.19). Subjects with multiple DGBI were at increased risk of having rumination syndrome, with the highest risk in subjects with 4 gastrointestinal regions with DGBI (OR, 15.9 compared with none). Quality of life (QoL) was lower in subjects with rumination syndrome compared with the rest of the cohort (PROMIS-10 score: physical QoL mean 12.9 vs 14.5; mental QoL mean 12.0 vs 13.6). CONCLUSIONS: The prevalence of rumination syndrome is higher than reported in most previous population studies and is likely underdiagnosed in clinical practice. Awareness of rumination syndrome should be raised among clinicians to improve care for these patients.

Identification of irritable bowel syndrome in the Swedish National Patient Register: a validation study.

BACKGROUND AND OBJECTIVE: National patient registers are valuable in epidemiological studies. To ensure high-quality data for studies of irritable bowel syndrome (IBS), this study aimed to validate the ICD-10 code for IBS in the Swedish National Patient Register. METHODS: The positive predictive values (PPV) for IBS defined by the Rome criteria were calculated based on a review of medical records of randomly selected individuals with a first-ever diagnostic listing of IBS in the Swedish National Patient register in the year 2005 (Rome II criteria) or 2010 (Rome III criteria). KEY RESULTS: 340 medical records were reviewed (172 from 2005 and 168 from 2010). The majority of patients were females (74%), and the mean age was 42 years. IBS used in any type of department had a PPV of 76% (95% confidence interval 71-80%), which increased to 80% (76-84%) when we included individuals likely to have IBS but where information about some aspects of the Rome criteria was lacking in the medical record. Two highly specialized gastroenterological departments had the best PPV, 96%, while departments of internal medicine in general had a PPV of 82% (80-95%). The PPV for the IBS subtype was 62% (55-67%). The PPVs were not significantly different comparing the two time periods investigated. CONCLUSION AND INFERENCES: The validity of a register-based definition of IBS in the Swedish National Patient register is high and can be used to identify patients with IBS in observational research. The data source, i.e., type of hospital and department, influences reliability.

Food Avoidance and Restriction in Irritable Bowel Syndrome: Relevance for Symptoms, Quality of Life and Nutrient Intake.

BACKGROUND & AIMS: Neither food intake nor the clinical characteristics of irritable bowel syndrome (IBS) patients with severe food avoidance and restriction have been investigated. The aim of our study was to identify those patients and to characterize their symptoms, quality of life, and nutrient intake. METHODS: IBS patients who completed the IBS Quality of Life Instrument (IBS-QOL) at our secondar and tertiary center were included. The 3 questions constituting the food domain were used to identify patients with reported severe food avoidance and restriction. The patients also completed validated questionnaires to assess stool form (Bristol Stool Form), gastrointestinal (GI) symptom severity (z score of IBS Severity Scoring System and Gastrointestinal Symptom Rating Scale-IBS), psychological distress (Hospital Anxiety and Depression Scale), GI-specific anxiety (Visceral Sensitivity Index), and somatic symptom severity (z score of Symptom Checklist-90-Revised and Patient Health Questionnaire-15). A 4-day food diary was used to analyze food intake in 246 patients. RESULTS: We included 955 IBS patients (75 % women; mean age 38.3 ± 13.3 years). In total, 13.2 % of the patients reported severe food avoidance and restriction, and in these patients all aspects of quality of life were lower (P < .01) and psychological, GI, and somatic symptoms were more severe (P < .05). Reported severe food avoidance and restriction was associated with lower total energy intake (P = .002) and lower intake of protein (P = .001) and carbohydrates (P = .005). In a logistic regression analysis, loose stools were found to be independently associated with reported severe food avoidance and restriction (R2 = 0.062). CONCLUSIONS: IBS patients with severe food avoidance and restriction constitute a subgroup with more severe symptoms overall, reduced quality of life, and reduced intake of nutrients. This needs to be acknowledged in the clinical management of these patients.

Chronic Constipation as a Risk Factor for Colorectal Cancer: Results From a Nationwide, Case-Control Study.

BACKGROUND & AIMS: Prolonged colon transit times may increase the contact time between potential carcinogens in the stool and the colonic mucosa. Nonetheless, previous studies have yielded conflicting results connecting chronic constipation with the risk of colorectal cancer (CRC). We examined the association between chronic constipation and later CRC. METHODS: In this nationwide case-control study, we identified 41,299 CRC cases by colorectal biopsy in Sweden between July 2007 and December 2016 and matched them to 203,181 age- and sex-matched controls from the general population. We compared odds of earlier chronic constipation (defined as ≥2 laxative prescriptions in the Prescribed Drug Register with ≥6 months between the first and last prescription) between CRC cases and controls using logistic regression. In separate analyses, we compared odds of earlier constipation between CRC cases and sibling comparators, but also examined earlier risk of having an inpatient/outpatient specialty diagnosis of chronic constipation before CRC. RESULTS: Overall, 3943 patients with CRC met our criteria for chronic constipation before CRC. The crude proportion of chronic constipation in CRC patients was 9.5% compared with 8.8% in controls. After multivariable adjustment, there was a modest association between chronic constipation and later CRC (odds ratio [OR], 1.10; 95% CI, 1.06-1.14) that vanished using sibling comparators to control for residual confounding (OR, 1.04; 95% CI, 0.97-1.13). In a sensitivity analysis of 126,650 CRC patients diagnosed from 1989 to 2016, we found no association with earlier chronic constipation diagnosed in inpatient/outpatient specialty clinics (OR, 0.88; 95% CI, 0.75-1.04). CONCLUSIONS: In a nationwide case-control study, chronic constipation was not associated with later CRC.

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.

Evidence-Based and Emerging Dietary Approaches to Upper Disorders of Gut-Brain Interaction.

Food ingestion is a major symptom trigger in functional esophageal and gastroduodenal disorders and gastroparesis. This review summarizes current knowledge and identifies areas of research on the role of food factors and the opportunities for dietary intervention in these disorders. While many patients experiencing functional esophageal and gastroduodenal disorders identify specific food items as symptom triggers, available data do not allow the identification of specific nutrient groups that are more likely to induce symptoms. In functional dyspepsia (FD), recent studies have shown the potential efficacy of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, although the underlying mechanism of action is unclear. Reports of favorable responses to gluten elimination in patients with FD are confounded by the concomitant benefit of reduced intake of fructans, fermentable oligosaccharides, disaccharides, monosaccharides, and polyols present in wheat. Emerging data based on a 6-food elimination diet and confocal laser endomicroscopic evaluation of mucosal responses to food proteins suggest a role for duodenal allergic reactions in FD symptom generation. In patients with gastroparesis, a low-residue diet has been shown to improve symptoms. Novel dietary approaches under evaluation are the Mediterranean diet and the heating/cooling diet approach.

Global prevalence and burden of meal-related abdominal pain.

BACKGROUND: Patients with disorders of gut-brain interaction (DGBI) report meal intake to be associated with symptoms. DGBI patients with meal-related symptoms may have more severe symptoms overall and worse health outcomes, but this subgroup has not been well characterized. We aimed to describe the global prevalence of meal-related abdominal pain and characterize this subgroup. METHODS: The data analyzed originated from the Internet survey component of the population-based Rome Foundation Global Epidemiology Study, completed in 26 countries (n = 54,127). Adult subjects were asked whether they had abdominal pain and how often this was meal-related. Respondents were categorized into "no," "occasional," and "frequent" meal-related abdominal pain groups based on 0%, 10-40%, and ≥50% of the pain episodes being meal-related, respectively. DGBI diagnoses, frequency of other GI symptoms, psychological distress, non-GI somatic symptoms, quality of life, and healthcare utilization were compared between groups. Mixed linear and ordinal regression was used to assess independent associations between psychological distress, non-GI somatic symptoms, quality of life, other GI symptoms, and meal-related abdominal pain. RESULTS: Overall, 51.9% of the respondents reported abdominal pain in the last 3 months, and 11.0% belonged to the group with frequent meal-related abdominal pain, which included more females and younger subjects. DGBI diagnoses were more common in subjects with frequent meal-related abdominal pain, and the frequency of several GI symptoms was associated with having more frequent meal-related abdominal pain. Having meal-related abdominal pain more frequently was also associated with more severe psychological distress, non-GI somatic symptoms, and a poorer quality of life. The group with frequent meal-related abdominal pain also more often consulted a doctor for bowel problems compared to the other groups of meal-related abdominal pain. CONCLUSION: Reporting frequent meal-related abdominal pain is common across the globe and associated with other GI and non-GI somatic symptoms, psychological distress, healthcare utilization, and a poorer quality of life. Individuals who frequently experience meal-related abdominal pain also more frequently fulfill the diagnostic criteria for DGBI. Assessing meal-related symptoms in all DGBI patients could be of major importance to improve and individualize symptom management.

Relationship Between Abuse History and Gastrointestinal and Extraintestinal Symptom Severity in Irritable Bowel Syndrome.

OBJECTIVE: This study aimed to investigate the associations between the different abuse types, and gastrointestinal (GI) and extraintestinal symptom severity in irritable bowel syndrome (IBS), and possible mediators of these relationships. METHODS: We assessed sexual and physical abuse in childhood and adulthood with the Drossman and Leserman abuse questionnaire, whereas GI and extraintestinal symptoms were assessed with the Gastrointestinal Symptom Rating Scale and the Symptom Check List-90 Revised. General linear models with bootstrapping tested the mediating role of depressive symptoms, anxiety symptoms, and GI-specific anxiety and rectal pain threshold. A path model analysis testing all relationships simultaneously was also performed. RESULTS: Among our 186 patients with IBS, an overall history of abuse (i.e., at least one type) was found in 37%. The effects of child and adult sexual abuse on GI symptom severity were fully mediated by GI-specific anxiety and rectal pain threshold (F = 21.540, R2 = 0.43, and F = 22.330, R2 = 0.44, respectively; p < .001 for both). The effect of adult sexual abuse and child physical abuse on extraintestinal symptom severity was fully mediated by GI-specific anxiety, depressive symptoms, and rectal pain threshold, whereas the effect of child sexual abuse was partially mediated (F = 14.992, R2 = 0.28; F = 15.065, R2 = 0.30; and F = 18.037, R2 = 0.32, respectively; p < .001 for all). When analyzed in a single path model, child sexual abuse and adult physical abuse only had a direct effect on extraintestinal symptom severity, whereas child physical abuse had an indirect effect through depressive symptoms. CONCLUSIONS: Abuse is associated with increased GI and extraintestinal symptom severity in IBS. These associations are mediated by levels of GI-specific anxiety, depressive symptoms, and rectal sensitivity.

Maintaining work life under threat of symptoms: a grounded theory study of work life experiences in persons with Irritable Bowel Syndrome.

BACKGROUND: Irritable Bowel Syndrome (IBS) is a highly prevalent functional gastrointestinal disorder. Earlier studies have shown that IBS can limit the ability to perform at work and lead to absenteeism. However, few studies focus on work life experiences based on patients' narratives. The purpose of this study was to construct a theory for how persons with IBS maintain their work life. METHODS: A qualitative study was performed using constructivist grounded theory. Semi-structured interviews with 15 women and 8 men with IBS (26-64 years of age) were conducted. Fourteen participants worked full-time, six worked part-time and three were on sick leave. The interviews were transcribed verbatim and coded line-by-line, incident-by-incident and thereafter focused coding was done. From the data and codes, categories were generated. Finally, a core category was constructed explaining the process of maintaining work life when living with IBS. RESULTS: Balancing work life while being under threat of symptoms constituted of four categories, being prepared, restricting impact, reconciling and adjusting. Persons with IBS restricted the impact of IBS on work by using strategies and upholding daily routines and strived to being prepared by exerting control over work life. These ongoing processes served to limit the influence of IBS on work by symptoms being less intense, perceived as less frequent, or not as bothersome. Reconciling IBS with work life was understood as a successful outcome from being prepared and restricting impact but was also influenced by the individual's outlook on life. Adjusting to other people at work interfered with the strategies of being prepared, restricting impact, and reconciling, leaving persons with IBS more susceptible to symptoms. CONCLUSIONS: This study deepens the understanding of the work situation for persons with IBS. Health care professionals can use the results of this study in the dialogue with the patient discussing work ability and sick leave. The results imply that although balancing work life under threat of symptoms can be a struggle, there are strategies that persons with IBS and employers together can initiate and use to reduce impact on work on several different levels.

Fecal Luminal Factors from Patients with Gastrointestinal Diseases Alter Gene Expression Profiles in Caco-2 Cells and Colonoids.

Previous in vitro studies have shown that the intestinal luminal content, including metabolites, possibly regulates epithelial layer responses to harmful stimuli and promotes disease. Therefore, we aimed to test the hypothesis that fecal supernatants from patients with colon cancer (CC), ulcerative colitis (UC) and irritable bowel syndrome (IBS) contain distinct metabolite profiles and establish their effects on Caco-2 cells and human-derived colon organoids (colonoids). The metabolite profiles of fecal supernatants were analyzed by liquid chromatography-mass spectrometry and distinguished patients with CC (n = 6), UC (n = 6), IBS (n = 6) and healthy subjects (n = 6). Caco-2 monolayers and human apical-out colonoids underwent stimulation with fecal supernatants from different patient groups and healthy subjects. Their addition did not impair monolayer integrity, as measured by transepithelial electrical resistance; however, fecal supernatants from different patient groups and healthy subjects altered the gene expression of Caco-2 monolayers, as well as colonoid cultures. In conclusion, the stimulation of Caco-2 cells and colonoids with fecal supernatants derived from CC, UC and IBS patients altered gene expression profiles, potentially reflecting the luminal microenvironment of the fecal sample donor. This experimental approach allows for investigating the crosstalk at the gut barrier and the effects of the gut microenvironment in the pathogenesis of intestinal diseases.

Association between Brachyspira and irritable bowel syndrome with diarrhoea.

OBJECTIVE: The incidence of IBS increases following enteric infections, suggesting a causative role for microbial imbalance. However, analyses of faecal microbiota have not demonstrated consistent alterations. Here, we used metaproteomics to investigate potential associations between mucus-resident microbiota and IBS symptoms. DESIGN: Mucus samples were prospectively collected from sigmoid colon biopsies from patients with IBS and healthy volunteers, and their microbial protein composition analysed by mass spectrometry. Observations were verified by immunofluorescence, electron microscopy and real-time PCR, further confirmed in a second cohort, and correlated with comprehensive profiling of clinical characteristics and mucosal immune responses. RESULTS: Metaproteomic analysis of colon mucus samples identified peptides from potentially pathogenic Brachyspira species in a subset of patients with IBS. Using multiple diagnostic methods, mucosal Brachyspira colonisation was detected in a total of 19/62 (31%) patients with IBS from two prospective cohorts, versus 0/31 healthy volunteers (p<0.001). The prevalence of Brachyspira colonisation in IBS with diarrhoea (IBS-D) was 40% in both cohorts (p=0.02 and p=0.006 vs controls). Brachyspira attachment to the colonocyte apical membrane was observed in 20% of patients with IBS and associated with accelerated oro-anal transit, mild mucosal inflammation, mast cell activation and alterations of molecular pathways linked to bacterial uptake and ion-fluid homeostasis. Metronidazole treatment paradoxically promoted Brachyspira relocation into goblet cell secretory granules-possibly representing a novel bacterial strategy to evade antibiotics. CONCLUSION: Mucosal Brachyspira colonisation was significantly more common in IBS and associated with distinctive clinical, histological and molecular characteristics. Our observations suggest a role for Brachyspira in the pathogenesis of IBS, particularly IBS-D.

Prevalence of Rome IV Functional Bowel Disorders Among Adults in the United States, Canada, and the United Kingdom.

BACKGROUND & AIMS: Little is known about the population prevalence or demographic distributions of Rome IV functional bowel disorders (FBDs) or their effects on quality of life. We examined these in a multinational survey. METHODS: We analyzed data from a population-based survey of adults in the United States, Canada, and United Kingdom (5931 valid responders; 49.2% female; mean age, 47.4 years; range, 18-92 years). The survey included the Rome IV Diagnostic Questionnaire, Rome III irritable bowel syndrome (IBS) and constipation questions, and the SF-8 quality of life questionnaire. RESULTS: The prevalence values of census-adjusted Rome IV FBDs were similar among the 3 countries; ranges were: 4.4%-4.8% for IBS, 7.9%-8.6% for functional constipation, 3.6%-5.3% for functional diarrhea, 2.0%-3.9% for functional bloating or distention, 1.1%-1.9% for opioid-induced constipation, 7.5%-10.0% for unspecified FBDs, and 28.6%-31.7% for any Rome IV FBD. FBDs were less common in older individuals, and all except functional diarrhea were more common in women. IBS was only half as prevalent by Rome IV as by Rome III criteria (4.6% vs 9.0% overall), primarily due to higher Rome IV minimum pain frequency. Functional diarrhea and functional constipation were more prevalent by Rome IV than Rome III criteria. Subjects with FBD had significant reductions in quality of life and reported more gastrointestinal doctor consultations than other subjects. CONCLUSIONS: More than 1 in 4 adults in the general population meet the Rome IV criteria for FBDs. These disorders affect quality of life and increase use of gastrointestinal health care. The switch from Rome III to Rome IV criteria reduces the prevalence of IBS by half, but increases the prevalence of functional constipation and functional diarrhea.

Online Education Is Non-Inferior to Group Education for Irritable Bowel Syndrome: A Randomized Trial and Patient Preference Trial.

BACKGROUND & AIMS: Structured education can reduce symptoms in patients with irritable bowel syndrome (IBS), but the availability of such interventions is limited and online formats could facilitate their dissemination. We compared the effectiveness of Internet-delivered vs face-to-face education in patients with IBS, hypothesizing that the online format would not be inferior. METHODS: We conducted 2 trials of Internet-delivered vs face-to-face group education (3 weeks) at a gastroenterology outpatient clinic in Sweden. In the first trial, 141 patients with IBS were assigned randomly (1:1) to either Internet-delivered or face-to-face education, from August 2016 through June 2017. In the second trial, 155 patients with IBS were allowed to choose whether to receive education via the Internet or face to face, from August 2017 through September 2018. Patients completed questionnaires before, during, and after education. The primary outcome measure was the irritable bowel syndrome severity scoring system, which measures IBS severity on a scale from 0 to 500, based on abdominal pain, bloating, dissatisfaction with bowel habits, and interference with life. The primary test of noninferiority adhered to the intent-to-treat principle and concerned the difference in change up to 6 months after education, tested using the 1-sided CI for the time by group interaction in a linear mixed model fitted on data from the randomized controlled trial. A secondary per-protocol analysis used data from all treatment completers in both trials. The noninferiority margin was 40 points on the irritable bowel syndrome severity scoring system. RESULTS: In the primary analysis, patients who received face-to-face education had an average reduction in irritable bowel syndrome severity score that was 12.2 points more than that of patients who received Internet education (1-sided 95% CI upper bound, 38.4). In the per-protocol analysis, patients who received face-to-face education reduced their average irritable bowel syndrome severity score by 14.7 points more than patients who received Internet education (95% CI upper bound, 35.5). Face-to-face education had significantly higher credibility and produced a significantly larger increase in self-rated knowledge, although most patients preferred Internet-delivered education. Between-group effects on secondary symptoms were small. CONCLUSIONS: Based on the comparison of Internet-delivered vs face-to-face education for IBS, the upper bound of the CI for the difference in change up to 6 months after education was within the noninferiority margin of 40 points. We therefore conclude that Internet-delivered education is noninferior to face-to-face education. Future research should focus on increasing within-group effects. ClinicalTrials.gov no: NCT03466281.

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.

Prevalence and Progression of Recurrent Abdominal Pain, From Early Childhood to Adolescence.

BACKGROUND & AIMS: Little is known about the natural history of childhood recurrent abdominal pain (RAP). We investigated the prevalence and progression of childhood RAP and its association with Rome III abdominal pain-related functional gastrointestinal disorders (AP-FGID) and irritable bowel syndrome (IBS) during adolescence. METHODS: We collected data from a prospective population-based birth cohort study of 4089 children, born from 1994 through 1996 in Sweden. We analyzed data from 2455 children with complete follow-up evaluation at ages 1, 2, 12, and 16 years and no parent-reported diagnoses of inflammatory bowel diseases or celiac disease at ages 12 or 16 years. A subpopulation of 2374 children who had answered questions based on the Rome III criteria at age 16 years was identified. We assessed RAP at 3 assessment points and defined it as parent-reported attacks of colic in early childhood (1-2 years) and as self-reported weekly abdominal pain at ages 12 years and 16 years. AP-FGID at age 16 years was defined according to the Rome III criteria. RESULTS: RAP was reported by 26.2% of children on at least 1 of 3 assessment points, of which 11.3% reported symptoms more than once. Children with RAP at 12 years had persistent symptoms at 16 years in 44.9% of cases and increased risks for RAP (relative risk, 2.2; 95% CI, 1.7-2.8), any AP-FGID (relative risk, 2.6; 95% CI, 1.9-3.6), and IBS (relative risk, 3.2; 95% CI, 2.0-5.1) at 16 years. Early childhood RAP was not associated significantly with any outcome. CONCLUSIONS: RAP affects many children from early childhood through age 16 years, but most children do not have persistent symptoms throughout childhood. RAP at age 12 years is a risk factor for RAP, any Rome III AP-FGID, and IBS, at age 16 years.

Cumulative Effect of Psychological Alterations on Gastrointestinal Symptom Severity in Irritable Bowel Syndrome.

INTRODUCTION: Psychological alterations are common and considered important for symptom generation in irritable bowel syndrome (IBS). However, the possible cumulative effect of having multiple psychological alterations on gastrointestinal (GI) symptom severity in IBS is largely unknown. METHODS: Patients with IBS (Rome IV) completed validated questionnaires assessing GI symptoms (Gastrointestinal Symptom Rating Scale, IBS version and IBS Severity Scoring System), personality traits (Big Five), posttraumatic stress and psychological alterations, anxiety (Generalized Anxiety Disorder 7-item scale and State-Trait Anxiety Inventory), depression (Patient Health Questionnaire, 9-item version), fatigue (Multidimensional Fatigue Inventory), pain catastrophizing, somatization (Patient Health Questionnaire, 12-item version), stress (Perceived Stress Scale), and GI-specific anxiety (Visceral Sensitivity Index). Of the 18 possible psychological factors, those with significant associations with GI symptom severity, corrected for multiple comparisons, were identified. The associations between increasing number of psychological alterations (validated cutoff values or uppermost tertile) and the severity of GI symptoms were analyzed with linear trend analyses. RESULTS: In total, 106 patients with IBS (Rome IV criteria) were included (72 [68%] women, median age of 35 [interquartile range: 26-45] years). Psychological alterations were common and overlap among these factors were frequently seen. Five psychological factors (physical fatigue, GI-specific anxiety, perceived stress, pain catastrophizing, and trait anxiety) demonstrated significant, noncollinear associations with GI symptom severity. With increasing number of these psychological alterations, a gradual increase was seen in the overall severity of GI symptoms (Gastrointestinal Symptom Rating Scale, IBS version: partial η = 0.268, P < 0.001; IBS Severity Scoring System: partial η = 0.219, P < 0.001, both large effect sizes). DISCUSSION: Distinct associations were seen between the severity of GI symptoms and individual, as well as an increasing number of psychological alterations. This highlights the importance of understanding different psychological alterations for the disease burden in IBS (visual abstract, Supplementary Digital Content 1, http://links.lww.com/AJG/B756).