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BACKGROUND: Irritable bowel syndrome patients report reduced disease-specific quality of life (IBSQOL). Factors of potential relevance for QOL include gastrointestinal (GI), psychological, and somatic symptoms, demographics, and GI motor and sensory abnormalities. OBJECTIVE: The aim of our study was to evaluate the relative importance of these factors on the different IBSQOL dimensions. METHODS: We included irritable bowel syndrome (IBS) patients who completed validated questionnaires to assess QOL, stool form and frequency, GI symptom severity, psychological distress, GI-specific anxiety, sense of coherence, and overall somatic symptom severity. Patients also underwent tests for oroanal transit time and rectal sensitivity. The nine dimensions of IBSQOL and their average (overall IBSQOL) were used as outcome variables, and factors associated with these were assessed using general linear models. RESULTS: We included 314 IBS patients (74% female, mean age 36.3 ± 12.2 years). Higher stool frequency, GI and overall somatic symptom severity, psychological distress, and GI-specific anxiety were independently associated with reduced overall IBSQOL, with the model explaining 60% of the variance (p

Irritable Bowel Syndrome (IBS) negatively influences mental and physical quality of life (QoL), but factors that explain this impact are still unclear. Increasing evidence has associated IBS severity, psychological distress, somatic symptoms, and gastrointestinal (GI)-specific anxiety with QoL in IBS. The aim of this study is to further explore these associations and to analyze potential mediating factors.A total of 1017 IBS patients (69.3% female, mean age 40.6 years) who completed a QoL measure (SF-36) were included in this study. A proportion of these participants (N = 183; 72.7% female, mean age 41.7), who additionally completed psychological distress, somatic symptoms, and GI-specific anxiety measures, was included in the mediation analysis. This analysis was conducted via structural equation modelling to identify factors of importance for generic QoL, using a cross-sectional design.IBS patients reported lower QoL than what is observed in the general population, in particular regarding role limitations caused by health and emotional functioning, vitality, and social functioning. Female patients scored lower than male patients on most QoL dimensions. The effects of IBS severity on mental and physical QoL were mediated by GI-specific anxiety. In addition to GI-specific anxiety, depressive symptoms were also of importance for mental QoL, and somatic symptom severity for physical QoL.QoL is reduced in patients with IBS and GI-specific anxiety, depressive symptoms, and somatic complaints are particularly important for this outcome. Future trials should test the efficacy of psychological interventions specifically targeting these factors in improving QoL in IBS.

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.

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. 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. 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. 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 Rome III criteria proposed to subdivide functional dyspepsia (FD) into a postprandial distress syndrome (PDS) group, characterized by the presence of postprandial fullness and/or early satiety, and an epigastric pain syndrome (EPS) group, characterized by the presence of epigastric pain and/or epigastric burning. It has been suggested that different pathophysiological mechanisms underlie the symptom presentations in these subgroups that might determine treatment choices. The aim of this study was to investigate the prevalence of gastric sensorimotor dysfunction in the PDS, EPS, and overlap groups and to evaluate potential differential associations with dyspeptic symptom scores.Consecutive FD patients fulfilling Rome III criteria were recruited and they scored frequency of dyspeptic symptoms (postprandial fullness, early satiety, nausea, bloating, epigastric pain, and epigastric burning) over the past 3 months (0-5; 1=once a month or less, 2=two or three times a month, 3=once a week, 4=several times a week, 5=every day). The cumulative symptom score was calculated by adding up the score of these dyspeptic symptoms. Based on these symptom scores, the patients were subdivided into subgroups according to the Rome III consensus: (i) PDS, characterized by postprandial fullness and/or early satiety at least several times a week, (ii) EPS, characterized by epigastric pain and/or epigastric burning at least once a week, and (iii) overlap, fulfilling the criteria for both PDS and EPS. Gastric sensitivity and gastric accommodation were measured using barostat testing, and solid gastric emptying was determined using the [A total of 560 FD patients (165 men, age 41.8±0.7 years) were classified into PDS (n=131), EPS (n=50), and overlap (n=379) groups. The prevalence of gastric hypersensitivity, impaired gastric accommodation, and delayed gastric emptying were 37%, 37%, and 23%, respectively, without any differential distribution in Rome III subgroups (P=0.16, P=0.27, and P=0.39 respectively). Comparing the physiological parameters for these gastric sensorimotor functions, there was only a significant difference in the gastric half emptying time between subgroups, with the overlap group having a higher tExcept for gastric emptying in the overlap group, FD subgroups as defined by the Rome III criteria are not differentially associated with putative pathophysiological mechanisms. These observations question the utility of this classification for guiding therapeutic choices in clinical practice.

Background Granins have been implicated in the pathophysiology of irritable bowel syndrome (IBS) in adults. We sought to determine whether fecal granins are altered in children with IBS and associated with symptoms. Methods Children (7-12 years of age) with IBS and healthy controls (HC) kept daily pain and stool diaries for 2 weeks. Stool samples were analyzed for chromogranins A and B (CgA, CgB) and secretogranins II and III (SgII, SgIII). Children also completed psychological measures to assess anxiety, depression, somatization, and internalizing symptoms. Key results Fecal CgB and SgIII concentrations were higher in all the boys (IBS plus HC, n = 48) than in all the girls (IBS plus HC, n = 75) (P = 0.02 and P = 0.046, respectively). CgA and SgIII were greater in children with IBS (n = 52) vs HC (n = 69) (P = 0.01, P = 0.017, respectively). CgB and SgII did not differ between groups. In children with IBS, the number of pain episodes per week and mean daily pain rating correlated positively with all four granins. The number of stools per day correlated positively with CgB and SgII, and the percent of diarrheal stools (6 or 7 on the Bristol Scale) correlated inversely with all four granins in boys but not in girls. Fecal granins did not correlate with psychological measures. Conclusions and inferences As measured by fecal granins, there is evidence of neuroimmune activation in children with IBS. Granins are related to abdominal pain symptoms, stooling frequency, and stool form in children with IBS. Sex influences the fecal concentration of CgB and SgIII.

International audience; Altered fecal levels of chromogranins (Cg) and secretogranins (Sg) are demonstrated in irritable bowel syndrome (IBS), but their role in IBS pathophysiology remains unknown. This study aimed to determine if granins are associated with bacterial composition, immune activation and IBS symptoms. Protein levels of fecal granins (CgA, CgB, SgII and SgIII) were analysed with immunoassays. Mucosal mRNA expression of granins, TPH1 and immune markers were evaluated with RT-qPCR. 16S rRNA gene sequencing was performed on fecal and mucosal bacteria. The intestinal granin profile, based on fecal protein levels and mucosal mRNA expression, could not discriminate between IBS patients (n = 88) and healthy subjects (HS, n = 33). IBS patients dominated by high fecal or mucosal granin levels, respectively, did not differ in symptom or immune profiles. Fecal-dominated and mucosal-dominated granin clusters of IBS patients and HS, demonstrated separate fecal and mucosal bacterial profiles and high fecal abundance of granins were associated with a less diverse bacterial composition and the Bacteroides enterotype. The intestinal granin profiles of IBS patients and HS are linked to the intestinal bacterial composition, diversity and enterotypes. These findings suggest that granins may be one of several host-produced factors regulating the microbiota composition of the intestine.

BACKGROUND & AIMS: Genetic factors are believed to affect risk for irritable bowel syndrome (IBS), but there have been no sufficiently powered and adequately sized studies. To identify DNA variants associated with IBS risk, we performed a genome-wide association study (GWAS) of the large UK Biobank population-based cohort, which includes genotype and health data from 500,000 participants. METHODS: We studied 7,287,191 high-quality single nucleotide polymorphisms in individuals who self-reported a doctor's diagnosis of IBS (cases; n = 9576) compared to the remainder of the cohort (controls; n = 336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n = 249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories to obtain biological insights from the observed associations. RESULTS: We identified a genome-wide significant association on chromosome 9q31.2 (single nucleotide polymorphism rs10512344; P = 3.57 × 10-8) in a region previously linked to age at menarche, and 13 additional loci of suggestive significance (P < 5.0×10-6). Sex-stratified analyses revealed that the variants at 9q31.2 affect risk of IBS in women only (P = 4.29 × 10-10 in UK Biobank) and also associate with constipation-predominant IBS in women (P = .015 in the tertiary cohort) and harder stools in women (P = .0012 in the population-based sample). Functional annotation of the 9q31.2 locus identified 8 candidate genes, including the elongator complex protein 1 gene (ELP1 or IKBKAP), which is mutated in patients with familial dysautonomia. CONCLUSIONS: In a sufficiently powered GWAS of IBS, we associated variants at the locus 9q31.2 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS. ispartof: GASTROENTEROLOGY vol:155 issue:1 pages:168-179 ispartof: location:United States status: published

ObjectiveIBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase–isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase–isomaltase (SI) gene variants for their potential relevance in IBS.DesignWe sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p.Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population.ResultsCSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case–control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (pConclusionsSI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.

Microscopic examination of endoscopic biopsies forms the basis of acute cellular rejection (ACR) monitoring after intestinal transplantation (ITx). The endoscopy findings during acute rejection (AR) are known but a grading system for its severity is lacking. We designed and implemented a five-stage grading score based on acknowledged endoscopic features of AR, to allow a faster preliminary diagnosis of AR and intra- and interpatient comparisons.Two investigators reviewed and graded the endoscopy reports after 28 ITx using a novel score and correlated the results with pathology findings.We reviewed 512 ileoscopies: 370 examinations (74%) were normal (G0), 59 had mild alterations (erythema, edematous villi-G1) and 36 showed moderate changes (erosions, blunted villi-G2); 17 ileoscopies revealed advanced changes (ulcerations, villus loss-G3). In 18 endoscopies the changes were severe (mucosal loss-G4). Inter-reviewer agreement was very good (kappa = 0.81). Biopsies from 86 endoscopy sessions (17%) indicated ACR with 63 cases having moderate or severe ACR. For mild ACR the sensitivity of the score was 29% and the specificity was 86% whereas the positive (PPV) and negative predictive values (NPVs) were 14% and 93% respectively. During advanced ACR the sensitivity and specificity were 92% and 86%, respectively whereas the PPV and NPV were 49% and 98% respectively.Endoscopy alone has a limited ability to reliably diagnose intestinal ACR. We suggest a novel grading score summarizing ACR findings and allowing comparisons between intestinal graft endoscopies.

Fatigue is a symptom in patients with chronic gastrointestinal (GI) and liver diseases. Different instruments have been developed to assess the severity of fatigue and the 40-item Fatigue Impact Scale (FIS) is among the most widely used. Shorter versions of FIS include the 21-item Modified Fatigue Impact Scale (MFIS), and an eight-item version for everyday use. The study aimed to assess construct validity, reliability, and sufficiency of the raw score of the original FIS with 40 items, and examine the sufficiency of the 21 items from the Modified scale and the eight items of the Daily Fatigue Impact Scale (D-FIS), all of which are embedded in the 40-item scale.Patients with chronic GI or liver disease (n = 354) completed the FIS with 40 items. The majority (57%) was under the age of 55 years and approximately half were females (48%). Various item sets of FIS were derived which showed fit to the Rasch model.Local dependency and multidimensionality in FIS and the 21-item Modified scale were resolved with a testlet solution but the D-FIS showed local dependency and multidimensionality and differential item functioning (DIF) still remained. Two new item sets fulfilling unidimensionality and no DIF are suggested, one with 15 items and a six-item scale for daily use. The transformation table shows score-interval scale estimates for all these item sets.Both the FIS and the Modified scale can be used to measure fatigue albeit requiring some adjustment for DIF. The eight-item D-FIS is more problematic, and its summed score is not valid. Alternative 15- and 6-item versions presented in this paper can offer valid summed scores, and the transformation table allows transformation of raw scores and comparisons across all versions. Implications for rehabilitation The Fatigue Impact Scale and the Modified Fatigue Impact Scale can be used to measure fatigue after adjustments for differential item functioning. Alternative 15- and 6-item versions of Fatigue Impact Scale offer valid summed scores. The summed score for the Daily Fatigue Impact Scale is not valid. A transformation table with raw scores and Rasch transformed interval scale metric makes it possible to compare scores derived from the Fatigue Impact Scale, the Modified Fatigue Impact Scale and the proposed 15- and 6-item versions of Fatigue Impact Scale for research and/or clinical use.

Background & Aims There are few data from longitudinal studies of the gastrointestinal and psychologic features of irritable bowel syndrome (IBS). We studied within-person correlations among features of IBS, along with progression of gastrointestinal (GI) symptoms and quality of life, and factors associated with changes over time. Methods We performed a longitudinal study of 276 patients with IBS in Sweden (70% female; ages, 19–76 years) who completed questionnaires, each year for 5 years, about their GI symptom severity, quality of life, GI-specific anxiety, general anxiety, depression, and coping resources. We performed within-person correlation analyses, latent class growth analysis, and random-intercept cross-lagged panel analysis. Results Within-person correlations with GI symptom severity were strongest for quality of life (r = –0.56) and GI-specific anxiety (r = 0.47). Progression of GI symptom severity was defined based on 3 classes; the class with the highest mean levels of GI, depression, and (GI-specific) anxiety symptoms at baseline did not improve over the 5-year period, contrary to the other classes. GI-specific anxiety was associated with an increase in GI symptom severity and decrease in quality of life 1 year later (P Conclusions In a 5-year study of patients with IBS in Sweden, we found 3 classes of GI symptom development. We found levels of GI-specific anxiety to associate with GI symptom severity and quality of life 1 year later. Clinicians should be aware of GI-specific anxiety in patients with IBS, to identify patients at risk for lack of long-term symptom improvement with standard medical treatment.

BACKGROUND Associations between irritable bowel syndrome and other health problems have been described, but comprehensive reports are missing, especially in primary care. AIMS To investigate which health problems are associated with irritable bowel syndrome, how they cluster together and when they are typically diagnosed relative to irritable bowel syndrome. METHODS We used Intego, a general practice registry in Flanders, Belgium. Patients with an irritable bowel syndrome diagnosis (n = 13 701) were matched with controls without gastrointestinal diagnosis and controls with organic gastrointestinal disease. Long-term prevalences of 680 symptoms and diagnoses were compared between patients and controls. Results were summarised using functional enrichment analysis and visualised in a network and we calculated incidence rate ratios in the 10 years before and after the irritable bowel syndrome diagnosis for the network's key components. RESULTS Various symptoms and infections, but not neoplasms, were enriched in irritable bowel syndrome patients compared to both control groups. We characterised the comorbidities of irritable bowel syndrome as psychosocial health problems, urogenital symptoms and infections, musculoskeletal symptoms and other somatic symptoms. These had a uniform incidence in the years around the irritable bowel syndrome diagnosis, and did not structurally precede or follow irritable bowel syndrome. CONCLUSIONS Irritable bowel syndrome shares long-term associations with psychosocial health problems, urogenital symptoms and infections, musculoskeletal symptoms and other somatic symptoms in primary care. Clinicians are encouraged to take comorbidities into account when diagnosing and managing irritable bowel syndrome, as this may have important treatment implications.

The population prevalence, clinical characteristics, and associations for Rome IV functional dyspepsia are not known. Following the publication of the Rome IV criteria for functional gastrointestinal disorders, we aimed to assess the prevalence, characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults across the USA, Canada, and the UK.We sent an internet-based cross-sectional health survey to adults in the general population of three English-speaking countries: the USA, Canada, and the UK. We used quota-based sampling to generate demographically balanced and population-representative samples. Individuals were invited to complete an online questionnaire on general health, without mention that the purpose of this survey was to examine gastrointestinal symptoms. We excluded participants who failed two attention-test questions or were excessively inconsistent on the three gastrointestinal questions that were presented twice in the survey for this particular purpose. The survey enquired about demographics, health-care visits, medications, somatisation, quality of life, and symptom-based criteria for Rome IV functional dyspepsia as well as for irritable bowel syndrome (IBS) and functional heartburn. We made subsequent comparisons between participants with Rome IV functional dyspepsia and controls without dyspepsia. The primary objective was to identify participants who fulfilled symptom-based criteria for Rome IV functional dyspepsia and categorise them into postprandial distress syndrome, epigastric pain syndrome, or overlapping subtypes.6300 general population adults completed the health survey; 2100 each from the USA, Canada, and the UK. 369 responses were deemed inconsistent, leaving data for 5931 adults. Rome IV functional dyspepsia was significantly more prevalent in the USA (232 [12%] of 1949) than in Canada (167 [8%] of 1988) and the UK (152 [8%] of 1994; p0·0001). The subtype distribution was 61% postprandial distress syndrome, 18% epigastric pain syndrome, and 21% overlapping variant with both syndromes; this pattern was similar across the countries. Participants with functional dyspepsia had significantly greater health impairment and health-care usage than those without dyspepsia. Participants with the overlapping variant showed greater somatisation and poorer quality-of-life scores than did individuals with either postprandial distress syndrome or epigastric pain syndrome alone. In multivariate analysis, independent factors associated with all functional dyspepsia subtypes included worsening quality of life and the presence of symptoms compatible with functional heartburn and IBS, with functional heartburn and IBS having the strongest association with overlapping postprandial distress syndrome and epigastric pain syndrome. Notably, somatisation showed a positive association with postprandial distress syndrome and the overlapping variant, and use of antidepressants showed a negative association with postprandial distress syndrome.Approximately 10% of the adult population fulfils symptom-based criteria for Rome IV functional dyspepsia and incurs considerable associated health impairment. The functional dyspepsia subtypes show differing associations, suggesting differences in pathophysiological processes or influences.The Rome Foundation, the US National Institute of Diabetes and Digestive and Kidney Diseases, the Swedish Medical Research Council, AFA Insurance, Ferring Pharmaceuticals, and the Faculty of Medicine, University of Gothenburg, Gothenburg, Sweden.

The population prevalence of Rome IV-diagnosed functional gastrointestinal disorders (FGIDs) and their cumulative effect on health impairment is unknown.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.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 P0.001. Notably, individuals with FGIDs in multiple regions had greater somatization and worse QOL than organic GI disease controls.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.

Irritable bowel syndrome (IBS) is common in western Europe and North America, and many aspects of its epidemiology, risk factors, and natural history have been described in these regions. Recent data suggest, however, that IBS is also common in the rest of the world and there has been some evidence to suggest some differences in demographics and presenting features between IBS in the west and as it is experienced elsewhere. The World Gastroenterology Organization, therefore, established a Task Force comprising experts on the topic from all parts of the world to examine IBS from a global perspective. IBS does, indeed, seem to be common worldwide though with some significant variations in prevalence rates between regions and countries and there may well be some potentially interesting variations in presenting symptoms and sex distribution. The global map of IBS is far from complete; community-based prevalence data is not available from many areas. Furthermore, while some general trends are evident in terms of IBS impact and demographics, international comparisons are hampered by differences in diagnostic criteria, study location and methodology; several important unanswered questions have been identified that should form the basis for future collaborative research and have the potential to shed light on this challenging disorder. © 2012 by Lippincott Williams & Wilkins.

Background In a previous clinical sample of IBS patients, subgroups characterized by profiles of GI and non-GI symptoms were identified. We aimed to replicate these subgroups and symptom associations in participants fulfilling IBS diagnostic criteria from a population-based study and relate them to healthcare utilization. Methods An Internet-based health survey was completed by general population adults from United States, Canada, and UK. Respondents fulfilling IBS diagnosis (Rome III and IV) were analyzed for latent subgroups using Gaussian mixture model analysis. Symptom measures were derived from validated questionnaires: IBS-related GI symptoms (Rome IV), extraintestinal somatic symptoms (PHQ-12), and psychological symptoms (SF-8). Key results A total of 637 respondents fulfilled Rome III criteria (average age 46 years, range 18-87, 66% females) and 341 Rome IV criteria (average age 44, range 18-77, 64% female) for IBS. Seven subgroups were identified in the Rome III cohort, characterized by profiles of GI symptoms (constipation-related, diarrhea-related, and mixed, respectively), and further distinguished by the presence or absence of non-GI comorbidities. The Rome IV cohort showed five similar but less distinct subgroups with a preponderance of mixed symptom profiles. Higher severity of non-GI comorbidities was associated with more frequent healthcare visits and medication usage. Conclusions and inferences In line with previous findings in a clinical IBS cohort, we were able to identify population-based subgroups characterized by a combination of GI symptoms with the additional distinction made by varying severity of non-GI symptoms and with differences in healthcare utilization.

Patients with irritable bowel syndrome (IBS) have an increased response of postprandial symptoms to a combined lactulose nutrient challenge test, compared with healthy volunteers. We investigated the associations among comorbid functional dyspepsia (FD), severity of psychologic symptoms, and breath test results in response to this test.We performed a prospective study of 205 patients with IBS (Rome III criteria), 94 of whom also had FD (IBS-FD), and 83 healthy volunteers in Sweden from 2008 through 2015. All participants completed a breath hydrogen test after a 400-mL liquid meal with 25 g lactulose. Gastrointestinal (GI) symptom severity was assessed using a graded scale and digestive comfort was recorded before the meal and every 15 minutes until 240 minutes after the meal. GI symptom scores over time were compared between groups using linear mixed models with anxiety, depression, and somatization as covariates.Average levels of all GI symptoms varied over time among all groups (P.0001). Patients with IBS-FD had higher levels of bloating (P = .004), abdominal pain (P = .005), and lower levels of digestive comfort (P.01) than patients with only IBS. We observed a difference in increase in abdominal pain from baseline between IBS-FD and IBS groups (P = .013). Anxiety levels were associated with levels of all symptoms (all P.025) except abdominal pain, which was associated with somatization severity (P.0001). Furthermore, anxiety levels associated with level of exhaled hydrogen (P = .0042).In a prospective study of patients with IBS, we found those with FD to have increased GI symptoms before and after a liquid meal with lactulose. Anxiety and somatization have an independent additional effect. The presence of comorbid FD and levels of psychologic symptoms affect reports of food-related symptoms in patients with IBS. ClinicalTrial.gov no: NCT01252550.

International audience; Background Immune activity and gut microbiota may impact the pathophysiology of irritable bowel syndrome (IBS). We aimed to determine whether antibacterial gene expression of immune activity-defined IBS patients differed compared to healthy subjects (HS) and ulcerative colitis (UC) patients and whether antibacterial profiles reflected gut microbiota composition and IBS symptoms. Methods Key Results Expression of 84 antibacterial genes in biopsies from HS, IBS patients (clustered according to immune activity (systemic and intestinal cytokines): immunonormal or immunoactive), and UC patients was assessed by Human Antibacterial Response RT2 Profiler PCR Array. In IBS patients, 16S rRNA gene sequencing of fecal and mucosal bacteria was performed and symptom pattern and severity were assessed. Intestinal antibacterial gene expression profiles differed between IBS patients (n = 31) and HS (n = 16), but did not differ between IBS subgroups based on bowel habit predominance or symptom severity. Based on previously identified IBS clusters, IBS patients with normal (n = 15) and enhanced immune activity (n = 16) had clearly separate antibacterial gene expression profiles from active UC patients (n = 12) and differed compared to each other and to HS. The differences in antibacterial gene expression profiles between immunonormal and immunoactive IBS patients were also reflected in distinct fecal and mucosal microbiota composition profiles, but not in symptom pattern or severity. Conclusions & Inferences This study demonstrates an altered antibacterial gene expression profile in IBS patients compared to HS and UC patients. While not linked to symptoms, immune activity-defined IBS clusters showed different intestinal antibacterial gene expression and distinct fecal and mucosal bacterial profiles.

Background The etiology of irritable bowel syndrome (IBS) is poorly understood. Animal and human data suggest that early life stress may induce long-term changes in the nociceptive circuitry, but conclusive studies are lacking. Methods We identified all Swedish children born between 1973 and 1992 in the Swedish Medical Birth Register. We had access to all diagnostic codes for specialized (nonprimary care) outpatient visits 2001-2009 (the National Patient Register) and identified individuals who were diagnosed with IBS (ICD-10 code: K58) after 18 years of age. We compared incidence of IBS in individuals with and without pre- and perinatal stress using multivariable logistic regression. Key results 2 056 430 children were included in the study. After turning 18 years, 14 382 of them were diagnosed with IBS in specialized outpatient care. Neither high, nor low birth weight was a risk factor for IBS in young adults. Preterm birth was associated with lower occurrence of IBS (adjusted OR 0.82 [0.75-0.90]) and vaginal instrumental delivery and Cesarean delivery were associated with slightly increased odds of IBS (adjusted OR 1.14 [1.06-1.24] and 1.09 [1.03-1.16] respectively). Neonatal distress and respiratory distress were not associated with future IBS. Female gender was by far the strongest risk factor for IBS in young adults (adjusted OR 3.48 [3.34-3.63]). Conclusions & inferences In this large population-based study, we found that mode of delivery was associated with an increased risk for IBS in young adulthood, while other proxies for pre- and perinatal stress were not. Female gender remains the most important risk factor for IBS.

Background: Disturbed brain-gut interactions are assumed to be of importance for symptom generation in patients with irritable bowel syndrome (IBS). The autonomic nervous system (ANS) is part of the bidirectional brain-gut communication, but previous studies in IBS show diverging results. We aimed to identify subgroups of IBS patients with distinct ANS characteristics differentiating them from healthy controls (HC), and to study associations between ANS status and symptoms. Methods: Heart rate variability (HRV) was measured in IBS patients and HC (Holter monitoring: supine and standing positions with controlled respiration and ambulatory 24-hour period). Frequency (5 minutes, supine, standing) and time domains (24 hours, day, night) were analyzed. Validated questionnaires were used to measure gastrointestinal and psychological symptoms in patients. Patients and HC were compared on a univariate and multivariate level (principal component analysis [PCA] and orthogonal partial least squares discriminatory analysis (OPLS-DA)). Key Results: We analyzed 158 IBS patients (Rome III) and 39 HC. Patients differed significantly from HC in HRV parameters during daytime and in standing position. In the PCA, a majority of patients overlapped with HC, but the weighted means differed (P

Phasic fundic contractions induce transient increases in gastric wall tension and can be perceived in patients with functional dyspepsia. It is unclear whether phasic contractile activity contributes to postprandial symptoms. The aim of the study was to examine postprandial phasic contractility in functional dyspepsia in relation to pathophysiological, clinical, and demographic variables.A gastric barostat study was performed in 180 patients with functional dyspepsia and in 53 healthy control subjects. Sensitivity to distensions and the motor response to a standardized liquid meal were assessed. Phasic contractility in the proximal stomach was quantified using a motility index during three 30-min periods, namely, the preprandial period and the first and second postprandial periods. Unsuppressed phasic contractility after the meal was defined as motility index greater than mean + 2 SD in control subjects in at least one of the two postprandial periods. Relationships between unsuppressed phasic contractility and impaired accommodation, hypersensitivity, delayed gastric emptying, Helicobacter pylori (H. pylori) infection, symptom severity, and demographic factors were assessed.Patients demonstrated a higher motility index than did control subjects during the first (22.8 +/- 10.1 vs 20.3 +/- 6.8 ml/s; p = 0.04) but not the second (19.9 +/- 9.1 vs 18.7 +/- 6.9 ml/s; ns) postprandial 30-min period. The motility index before the meal was similar in patients and controls. Unsuppressed phasic contractility postprandially was observed in 15% of the patients. H. pylori infection (p = 0.01), relevant or severe bloating (p = 0.004), and absence of nausea (p = 0.004) were found to be independently associated with unsuppressed phasic contractility after a meal.Unsuppressed postprandial phasic contractility in the proximal stomach is present in a small subset of patients with functional dyspepsia. It is associated with relevant and severe bloating and H. pylori infection but also with the absence of nausea.

Duodenal acid has been suggested to be of importance for dyspeptic symptoms. We investigated the effects of acid on duodenal mechanosensitivity and antroduodenal motility in 10 healthy subjects before and during duodenal infusion of acid (0.1 N HCl) or water by using a combined barostat-manometry assembly. During acid infusion, increased sensitivity to balloon distension was seen, with reduced perception ( P = 0.04) and discomfort thresholds ( P = 0.06) and higher intensity of discomfort ( P = 0.02) compared with water. Higher balloon volumes were seen during acid infusion, indicating decreased tone ( P = 0.05). Large volume waves were more prevalent during acid than water infusion ( P = 0.009). The acid infusion suppressed antral contractions ( P = 0.04) and increased the number of contractions in the proximal duodenum ( P = 0.02) compared with before the infusion. In conclusion, duodenal acid enhances mechanical sensitivity in the duodenum, affects gastroduodenal motor function, and might be of importance for dyspeptic symptoms.

none 44 si IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies. open Ek, Weronica E; Reznichenko, Anna; Ripke, Stephan; Niesler, Beate; Zucchelli, Marco; Rivera, Natalia V; Schmidt, Peter T; Pedersen, Nancy L; Magnusson, Patrik; Talley, Nicholas J; Holliday, Elizabeth G; Houghton, Lesley; Gazouli, Maria; Karamanolis, George; Rappold, Gudrun; Burwinkel, Barbara; Surowy, Harald; Rafter, Joseph; Assadi, Ghazaleh; Li, Ling; Papadaki, Evangelia; Gambaccini, Dario; Marchi, Santino; Colucci, Rocchina; Blandizzi, Corrado; Barbaro, Raffaella; Karling, Pontus; Walter, Susanna; Ohlsson, Bodil; Tornblom, Hans; Bresso, Francesca; Andreasson, Anna; Dlugosz, Aldona; Simren, Magnus; Agreus, Lars; Lindberg, Greger; Boeckxstaens, Guy; Bellini, Massimo; Stanghellini, Vincenzo; Barbara, Giovanni; Daly, Mark J; Camilleri, Michael; Wouters, Mira M; D'Amato, Mauro Ek, Weronica E; Reznichenko, Anna; Ripke, Stephan; Niesler, Beate; Zucchelli, Marco; Rivera, Natalia V; Schmidt, Peter T; Pedersen, Nancy L; Magnusson, Patrik; Talley, Nicholas J; Holliday, Elizabeth G; Houghton, Lesley; Gazouli, Maria; Karamanolis, George; Rappold, Gudrun; Burwinkel, Barbara; Surowy, Harald; Rafter, Joseph; Assadi, Ghazaleh; Li, Ling; Papadaki, Evangelia; Gambaccini, Dario; Marchi, Santino; Colucci, Rocchina; Blandizzi, Corrado; Barbaro, Raffaella; Karling, Pontus; Walter, Susanna; Ohlsson, Bodil; Tornblom, Hans; Bresso, Francesca; Andreasson, Anna; Dlugosz, Aldona; Simren, Magnus; Agreus, Lars; Lindberg, Greger; Boeckxstaens, Guy; Bellini, Massimo; Stanghellini, Vincenzo; Barbara, Giovanni; Daly, Mark J; Camilleri, Michael; Wouters, Mira M; D'Amato, Mauro

Objective The complex genetic aetiology underlying irritable bowel syndrome (IBS) needs to be assessed in large-scale genetic studies. Two independent IBS cohorts were genotyped to assess whether genetic variability in immune, neuronal and barrier integrity genes is associated with IBS. Design 384 single nucleotide polymorphisms (SNPs) covering 270 genes were genotyped in an exploratory cohort (935 IBS patients, 639 controls). 33 SNPs with P-uncorrected

Objective. Development of ascites in patients with liver cirrhosis is an ominous sign with a poor outcome. A liver transplantation must be considered, and it then becomes important to know if there are any factors indicating a worsened prognosis. Material and methods. We used official registers for a follow-up study of at least 5 years considering the prognosis of 155 prospectively recruited in-patients with cirrhotic ascites from medical units at nine Swedish university hospitals. All patients had undergone at least one diagnostic ascites tap, and had initially been questioned about background factors and physically examined according to a standardized case record form, followed by sampling of blood, urine, and ascites. Results. Death occurred within 1 year after inclusion in 53% of the cases, and was primarily liver-related in 70%. In a multivariable analysis, the two ordinary variables that showed the strongest correlation with risk of death were serum potassium and abdominal tenderness. All 22 patients with a serum potassium concentration of at least 4.8 mmol/L (maximum 5.8 mmol/L) died within 1 year after inclusion. Potassium concentration was related to renal function and potassium-saving drugs. Conclusion. This follow-up study of a prospectively recruited cohort of in-patients with cirrhotic ascites confirms their poor prognosis. Awareness of an elevated serum potassium value, which would reflect a threatened renal function, seems essential, because it may offer a simple way to identify cases with the worst prognosis. An area for further research should be to explore the significance of including serum potassium in prognostic models.