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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. ispartof: GASTROENTEROLOGY vol:164 issue:7 pages:1211-1222 ispartof: location:United States status: published

Background Low-grade immune activation in the gut is a potential treatment target in irritable bowel syndrome (IBS). Aims To determine improvement in IBS symptoms after mesalazine treatment, and the utility of measures of immune activity in the rectal mucosa Methods This was a randomised, double-blind, placebo-controlled, parallel-arm, multicentre trial in subjects with IBS (Rome III criteria), with an eight-week treatment period of mesalazine 2400 mg or plcebo once-daily. The primary endpoint was the global assessment of satisfactory relief of IBS symptoms in ≥50% of weeks during intervention. IBS symptoms were also measured with the IBS severity scoring system; immune activity was measured by mucosal patch technology. A post hoc meta-analysis of randomised placebo-controlled trials of mesalazine in IBS was added. Results Of 181 included patients, 91 received mesalazine and 90 received placebo. The primary endpoint was met by 32 (36%) patients after mesalazine and 27 (30%) after placebo (p = 0.40). There were no differences in response rates related to IBS subtype or post-infection symptom onset. More reduction of abdominal bloating was noted in the mesalazine group (p = 0.02). The meta-analysis showed no effect of mesalazine on IBS symptoms. No mucosal patch technology measure could predict response to mesalazine, and found no differences in the effects of intervention on levels of immune markers. Conclusions Mesalazine is ineffective in reducing IBS symptoms. Rectal measures of immune activity by the mucosal patch technology cannot predict a higher chance of response to mesalazine. publishedVersion

Background and Objective\ud \ud To determine the population prevalence and associated health impairment of disorders of gut-brain interaction (DGBI) across Great Britain, and the emphasis placed upon them within medical education.\ud \ud \ud \ud Methods\ud \ud An Internet-based cross-sectional health survey was completed by 1906 general population adults across Great Britain without self-reported organic GI disease. The survey enquired for demographics, symptom-based criteria for Rome IV DGBI, healthcare use, non-GI somatic symptoms, and quality of life. As a separate analysis, we evaluated which DGBI are considered core knowledge at undergraduate medical school level and post-graduate specialization level for Gastroenterologists and General Practitioners.\ud \ud \ud \ud Results\ud \ud The overall prevalence of DGBI across Great Britain was 37%, being similar for England (37%), Scotland (33%), and Wales (36%); p = 0.66. There was no difference between English regions (range 33%–43%, p = 0.26). The prevalence of DGBI was highest in those aged 18–40 years (40%), then 40–64 years (37%), and least amongst those ≥65 years (29%); p < 0.001. The most common DGBI were bowel disorders (30%), followed by gastroduodenal (10.5%), anorectal (8.1%) and oesophageal disorders (6.2%). Individuals with DGBI were significantly more likely than those without DGBI to have increased GI-related healthcare visits, medication use, surgical interventions, non-GI somatic symptoms, and reduced quality of life. One-in-three people with DGBI had multiple GI organ regions involved and this correlated with increased health impairment (p < 0.001).\ud \ud \ud \ud The only DGBI mentioned across all medical training curricula is irritable bowel syndrome, while the General Practitioner and Gastroenterology Curricula also recognise the outdated term non-ulcer dyspepsia (as opposed to functional dyspepsia). The 2010 Gastroenterology Curriculum also includes functional constipation and disordered defecation, with the incoming 2022 iteration adding in functional upper GI syndromes, functional abdominal pain, and opioid-induced GI disturbances.\ud \ud \ud \ud Conclusion\ud \ud Disorders of gut-brain interaction are common across Great Britain and incur substantial health impairment. However, they are generally under-taught within the British medical education system. Increasing awareness and education of disorders of gut-brain interaction might improve patient outcomes.

The majority of patients with irritable bowel syndrome (IBS) experiences food-related symptoms, which are associated with high symptom burden, reduced quality of life, increased healthcare consumption and reduced intake of certain nutrients. In this review we aimed to describe a clinically useful approach for physicians, by presenting the latest progress in knowledge and its translation to management in IBS patients with food-related symptoms, as well as the underlying mechanisms involved. The research tools currently available that can be used in the future for a better characterization of this subgroup of patients are also discussed. Working towards this approach could lead to a more individualised work-up and management of IBS patients with food-related symptoms. ispartof: UNITED EUROPEAN GASTROENTEROLOGY JOURNAL vol:10 issue:6 pages:594-600 ispartof: location:England status: published

BACKGROUND: Previous epidemiologic studies in Sweden have only covered some of the disorders of gut-brain interaction (DGBI) and are not representative of the general population. This study aimed to define the prevalence and impact of DGBI in Sweden. METHODS: We used Swedish data from the Rome Foundation Global Epidemiology Study which include information on DGBI diagnoses, psychological distress, quality of life (QoL), healthcare utilization, and the impact of stress on GI symptoms. KEY RESULTS: The prevalence of having any DGBI was 39.1% (95% CI 37.0-41.2); esophageal disorders 6.1% (5.1-7.3), gastroduodenal disorders 10.7% (9.3-12.0), bowel disorders 31.6% (29.6-33.6), and anorectal disorders 6.0% (5.1-7.2). Subjects with a DGBI more commonly reported anxiety and/or depression, reduced mental and physical QoL, and more frequent doctor visits due to health problems. Subjects with a DGBI reported bothersome gastrointestinal (GI) symptoms to a greater extent and more than 1/3 had visited a doctor due to GI problems and of those 1/3 had seen multiple doctors. Prescription medications were available among 36.4% (31.0-42.0) who had bothersome GI symptoms and a DGBI, with sufficient symptom relief in 73.2% (64.0-81.1). Psychological factors and eating were reported to worsen GI symptoms and stress during the last month was greater in subjects with a DGBI. CONCLUSIONS AND INFERENCES: DGBI prevalence and its impact in Sweden is in line with global data, including increased healthcare utilization. GI symptoms are commonly affected by psychological factors and eating, and a high proportion of those on prescription medication report sufficient GI symptom relief. ispartof: NEUROGASTROENTEROLOGY AND MOTILITY vol:35 issue:6 ispartof: location:England status: accepted

Introduction : Symptoms of irritable bowel syndrome (IBS) are common reasons for endoscopic procedures. We examined the yield of colonoscopy and upper endoscopy in IBS for several organic diseases. Methods : Matched population-based prevalence study in Sweden. We identified 21,944 participants diagnosed with IBS from 1987 to 2016 undergoing colonoscopy with a biopsy from all of Sweden's 28 pathology departments within 6 months of diagnosis. We compared prevalence of histopathology-proven diagnoses of inflammatory bowel disease (IBD), colorectal cancer, precancerous polyps, and microscopic colitis between patients recently diagnosed with IBS and matched controls without IBS (n = 81,101) undergoing colonoscopy. We also compared prevalence of celiac disease between patients diagnosed with IBS (n = 9,965) and matched controls (n = 45,584) undergoing upper endoscopy with biopsy. IBS patients were also compared to their siblings. Conditioned logistic regression estimated adjusted odds ratios (aORs). Results : Biopsy-proven IBD was seen in 1.6% of IBS and in 5.9% of controls (aOR=0.21; 95%CI=0.19–0.24). The prevalence of precancerous polyps was 4.1% vs. 13.0% (aOR=0.28; 95%CI=0.26–0.30), colorectal cancer 0.8% vs. 6.3% (aOR=0.17; 95%CI=0.14–0.20) and celiac disease 1.9% vs. 3.4% (aOR=0.54; 95%CI=0.47–0.63). Conversely, the prevalence of microscopic colitis was 2.9% vs. 1.7% (aOR=1.77; 95%CI=1.61–1.95), with higher prevalence in older patients and patients with IBS with diarrhea. Yield of colonoscopy for precancerous polyps, colorectal cancer, and microscopic colitis increased by age. Our findings were consistent using unaffected siblings as the comparator group. Discussion : The diagnostic yield of upper endoscopy and colonoscopy for organic disease is low in patients with a first-time diagnosis of IBS, though increases with age.

Background Irritable bowel syndrome (IBS) is highly prevalent worldwide but mechanisms for healthcare seeking behaviours in this patient group are poorly understood. Objective To describe healthcare utilization and identify factors associated with seeking healthcare amongst IBS subjects in the general population. Methods An internet survey was completed by 6,300 individuals equally distributed between United States, United Kingdom and Canada. The Rome IV diagnostic questionnaire was used to identify subjects with IBS. Data on demographics, medical history, gastrointestinal (GI) and non‐GI symptoms, quality of life and health care consumption was collected. Results A total of 5,931 subjects were included; 274 (4.6%) IBS subjects and 5657 (95.3%) non‐IBS controls. IBS subjects reported more doctor consultations for both GI and other health problems as well as increased use of medication and rate of abdominal surgery (appendectomy excluded). Having healthcare insurance or access to free public healthcare (adjusted odds ratio (AOR) 4.49, 95% confidence interval (CI) 1.31–15.44), followed by high frequency of bloating (AOR 2.65, 95% CI 1.42–4.93) and increasing age (AOR 1.02, 95% CI 1.01–1.05) were found to be independently associated with being an IBS consulter while doctor‐diagnosed IBS subjects were more likely to be female and to report abdominal pain as their most bothersome GI symptom than other consulters with IBS. Conclusion IBS subjects have higher healthcare utilization than non‐IBS controls, medication use and abdominal surgery included. Furthermore, consulters with and without an IBS diagnosis differ in sex distribution and symptom profiles. Hence, awareness of the possibility of unnecessary medical and surgical treatment in IBS subjects and a sex‐related diagnostic bias by doctors is warranted.

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.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.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.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.

BACKGROUND: Abnormal oroanal transit time (OATT) and visceral hypersensitivity are key pathophysiological factors in irritable bowel syndrome (IBS). The lactulose nutrient challenge test (LNCT) has been developed to assess the postprandial symptoms and gut microbial fermentation. We aimed to investigate associations between OATT, rectal sensitivity, and LNCT in IBS patients. METHODS: We included 263 IBS patients from two study cohorts, where the link between pathophysiology and symptoms was investigated. During the LNCT, severity of postprandial symptoms was graded, and breath hydrogen/methane concentrations were measured after ingestion of a combined lactulose nutrient drink every 15 min for 4 h. The patients underwent rectal sensitivity (rectal barostat) and OATT (radiopaque markers) investigations. Comorbid conditions (functional dyspepsia, anxiety, depression, and somatization) were assessed with questionnaires. KEY RESULTS: After controlling for comorbid conditions, rectal sensitivity was associated with abdominal pain (p

A gluten-free diet reduces symptoms in some patients with irritable bowel syndrome (IBS) through unclear mechanisms.To assess the effects of gluten-free versus gluten-containing diet on symptoms and the gut microenvironment, and to identify predictors of response to the gluten-free diet in IBS METHODS: Twenty patients with IBS and 18 healthy controls (HC) followed a gluten-free diet during two 14-day intervention periods where they sprinkled either gluten (14 g/day) or rice flour powder over their meals. Primary outcomes included effects of the interventions on IBS symptoms (IBS-SSS) and bowel habits. Secondary outcomes included effects of gluten-free diet on faecal microbiota and metabolite profile.IBS symptoms improved during the gluten-free (p = 0.02), but not the gluten-containing period, with no difference between the interventions. IBS patients reported fewer loose stools during the gluten-free intervention (p = 0.01). Patients with IBS and HC presented distinct metabolite profiles based on the effects of the gluten-free diet (p 0.001). True responders (reduced IBS-SSS by ≥50 solely after gluten-free period) and non-responders were discriminated based on the effects of the gluten-free diet on the microbiota (p 0.01) and metabolite profiles (p 0.001). The response to the gluten-free diet could be predicted by the metabolite profile before the intervention (p 0.001).A gluten-free diet may influence symptoms in a subset of patients with IBS, with a particular effect on bowel habits. A gluten-free diet seems to impact the gut microenvironment. Responsiveness to the gluten-free diet may be predicted by the metabolite profile.gov: NCT03869359.

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

Alteration of the host-microbiota cross talk at the intestinal barrier may participate in the pathophysiology of irritable bowel syndrome (IBS). Therefore, we aimed to determine effects of fecal luminal factors from IBS patients on the colonic epithelium using colonoids.Colon-derived organoid monolayers, colonoids, generated from a healthy subject, underwent stimulation with fecal supernatants from healthy subjects and IBS patients with predominant diarrhea, phosphate-buffered saline (PBS), or lipopolysaccharide (LPS). Cytokines in cell cultures and fecal LPS were measured by ELISA and mRNA gene expression of monolayers was analyzed using Qiagen RTColonoid monolayers stimulated with fecal supernatants from healthy subjects (n = 7), PBS (n = 4) or LPS (n = 3) presented distinct gene expression profiles, with some overlap (RFecal luminal factors from IBS patients induce a distinct colonic epithelial gene expression, potentially reflecting the disease pathophysiology. The culture of colonoids from healthy subjects with fecal supernatants from IBS patients may facilitate the exploration of IBS related intestinal micro-environmental and barrier interactions.

BACKGROUND/OBJECTIVES: The global epidemiology of gastroparesis is unknown. The European UEG and European Society for Neurogastroenterology and motility consensus defines Gastroparesis as a condition characterized by delayed gastric emptying in the absence of mechanical obstruction, with a symptom pattern of nausea and/or vomiting and overlapping postprandial distress syndrome (PDS). Real-world evidence of this gastroparesis-like symptom pattern is a crucial step in understanding the epidemiology of gastroparesis. METHODS: In the Rome Foundation Global Epidemiology Study, 54,127 respondents from 26 countries completed the Rome IV Diagnostic Questionnaire and variables associated with disorders of gut-brain interaction via Internet. We selected subjects with gastroparesis-like symptoms (GPLS) (nausea and/or vomiting ≥1 day/week and simultaneous PDS). Patients reporting organic gastrointestinal disease, or fulfilling criteria for self-induced vomiting, cyclic vomiting or cannabinoid hyperemesis syndrome were excluded. We determined prevalence, associated comorbidities, quality of life (QoL) (PROMIS Global-10), symptoms of anxiety and depression (PHQ-4), somatic symptoms (PHQ-12), and healthcare utilization. RESULTS: The global prevalence of GPLS was 0.9% overall and 1.3% among diabetic individuals. Subjects with GPLS showed frequent overlapping of epigastric pain syndrome and irritable bowel syndrome. Subjects with GPLS had significantly lower body mass index, QoL, more non-gastrointestinal somatic complaints, symptoms of anxiety and depression, higher medication usage and doctor visits in the overall and diabetic population, compared to subjects without these symptoms. CONCLUSIONS: GPLS are common worldwide and more common in diabetic patients. The symptom complex is associated with multiple aspects of illness and an increased healthcare consumption. ispartof: UNITED EUROPEAN GASTROENTEROLOGY JOURNAL vol:10 issue:8 pages:888-897 ispartof: location:England status: published

Gastroesophageal reflux disease (GERD) often requires lifelong treatment to return to and maintain a normal quality of life. Proton pump inhibitors (PPIs) offer effective medical treatment and can be used for a long time with good safety margins. The diagnostic criteria for GERD must be strictly based on current guidelines and the need for maintained treatment must be regularly evaluated. When medical treatment fails (20%), the patient should be offered a consultation with a specialist in the field. Too many patients who are currently treated with PPI for suspected GERD ultimately require treatment with a completely different diagnosis in focus. The investigation and treatment options are several and well-defined in the event of PPI failure in patients with well documented GERD. The indications for surgical treatment are well established, but this treatment option is likely underused today.

Luiza Moraes Holst,1 Jonas Halfvarson,2 Marie Carlson,3 Charlotte Hedin,4 Robert Kruse,5 Carl Mårten Lindqvist,6 Daniel Bergemalm,2 Sven Almér,4 Francesca Bresso,7 Maria Ling Lundström,3 Dirk Repsilber,6 Mauro D’Amato,8– 10 Åsa Keita,11 Henrik Hjortswang,12 Johan Söderholm,11 Johanna Sundin,13 Hans Törnblom,14 Magnus Simrén,14,15 Hans Strid,16 Maria K Magnusson,1 Lena Öhman1 1Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 3Department of Medical Sciences, Uppsala University, Uppsala, Sweden; 4Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden; 5Department of Clinical Research Laboratory, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 6School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 7Karolinska University Hospital, Gastroenterology Unit, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden; 8Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; 9IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; 10Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Derio, Spain; 11Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; 12Department of Clinical and Experimental Science, Linköping University, Linköping, Sweden; 13Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden; 14Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 15Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 16Department of Internal Medicine, Södra Älvsborg Hospital, Borås, SwedenCorrespondence: Lena Öhman, Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, Tel +46703616499, Email lena.ohman@gu.seBackground: Improved mucosal immune profiling in active and quiescent colonic inflammatory bowel disease (IBD) is needed to develop therapeutic options for treating and preventing flares. This study therefore aimed to provide a comprehensive mucosal characterization with emphasis on immunological host response of patients with active ulcerative colitis (UC active), UC during remission (UC remission) and active colonic Crohn’s disease (CD active).Methods: Colonic biopsies from 47 study subjects were collected for gene expression and pathway analyses using the NanoString host-response panel, including 776 genes and 56 immune-related pathways.Results: The majority of mucosal gene expression and signaling pathway scores were increased in active IBD (n=27) compared to healthy subjects (n=10). However, both active IBD and UC remission (n=10) demonstrated decreased gene expression and signaling pathway scores related to autophagy, alpha kinase-1 and IL-17 signaling pathways compared to healthy subjects. Further, UC remission was characterized by decreased scores of several signaling pathways linked to homeostasis along with increased mononuclear cell migration pathway score as compared to healthy subjects. No major differences in the colonic mucosal gene expression between CD active (n=7) and UC (n=20) active were observed.Conclusion: This study indicates that autophagy, alpha kinase-1 and IL-17 signaling pathways are persistently downregulated in UC irrespective of disease activity. Further, UC patients in remission present a unique mucosal environment, potentially preventing patients from reaching and sustaining true homeostasis. These findings may enable better comprehension of the remitting and relapsing pattern of colonic IBD and guide future treatment and prevention of flares.Keywords: inflammatory bowel diseases, gene expression, mucosal transcriptome, homeostasis, host response

Fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) can provoke symptoms in patients with irritable bowel syndrome (IBS). We aimed to compare the effects of diets with low vs. moderate FODMAP content on gastrointestinal (GI) symptoms and bowel habits, and to identify possible predictors of clinical response to a low FODMAP diet and FODMAP sensitivity in IBS.Adult participants with IBS (Rome IV criteria, n = 29) were included and adhered to two 7-day diet periods, with either low (4 g/day) or moderate (23 g/day) amounts of FODMAPs, in this randomized, double-blind, crossover study. The periods were separated by a wash-out period (≥14 days). IBS-Severity Scoring System (IBS-SSS) and a stool diary (Bristol Stool Form) were completed before and after the diet periods. At baseline, severity of GI symptoms and gut microbial fermentation were assessed (every 15 min, 4 h) during the Lactulose Nutrient Challenge Test (LNCT). Clinical response and FODMAP sensitivity were defined by reduction after low FODMAP period, and increase after moderate FODMAP period in IBS-SSS (≥50 points), respectively.Severity of GI symptoms (P = 0.04), stool consistency (P = 0.01), and stool frequency (P = 0.01) differed between the interventions, with reduced overall GI symptom severity, abdominal pain intensity and frequency, bowel habits dissatisfaction, and daily life interference (P 0.05 for all), as well as more firm (P = 0.03) and less frequent (P 0.01) stools after low FODMAP intervention, but not after moderate FODMAP intervention. A third (34%) responded clinically to the low FODMAP diet, and the response could be predicted by higher IBS-SSS at baseline (P = 0.02). Although modest associations between FODMAP sensitivity (22%) and GI symptoms during LNCT were observed, no independent predictors could be identified.A diet low in FODMAPs reduces GI symptoms and affects bowel habits in IBS, compared with a moderate FODMAP diet. Assessment of IBS severity before the intervention may be used to predict clinical response to a low FODMAP diet. Trial registry (http://www.gov): Registered under Clinical Trial number NCT05182593.

ObjectiveThe 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.DesignMucus 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.ResultsMetaproteomic 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 (pBrachyspira 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.ConclusionMucosal 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.

Introduction Mortality concern is a frequent driver of care seeking in patients with irritable bowel syndrome (IBS). Data on mortality in IBS are scarce, and population-based studies have been limited in size. We examined mortality in IBS. Methods A nationwide, matched, population-based cohort study was conducted in Sweden. We identified 45,524 patients undergoing a colorectal biopsy at any of Sweden's 28 pathology departments and with a diagnosis of IBS from 2002 to 2016 according to the National Patient Register, a nationwide registry of inpatient and outpatient specialty care. We compared the mortality risk between these individuals with IBS and age- and sex-matched reference individuals (n = 217,316) from the general population and siblings (n = 53,228). In separate analyses, we examined the role of mucosal appearance for mortality in IBS. Finally, we examined mortality in 41,427 patients with IBS not undergoing a colorectal biopsy. Cox regression estimated hazard ratios (HRs) for death. Results During follow-up, there were 3,290 deaths in individuals with IBS (9.4/1,000 person-years) compared with 13,255 deaths in reference individuals (7.9/1,000 person-years), resulting in an HR of 1.10 (95% confidence interval [CI] = 1.05-1.14). After adjustment for confounders, IBS was not linked to mortality (HR = 0.96; 95% CI = 0.92-1.00). The risk estimates were neutral when patients with IBS were compared with their siblings. The underlying mucosal appearance on biopsy had only a marginal impact on mortality, and patients with IBS not undergoing a colorectal biopsy were at no increased risk of death (HR = 1.02; 95% CI = 0.99-1.06). Discussion IBS does not seem to confer an increased risk of death.

This study investigated immune profiles of ulcerative colitis (UC) patients and irritable bowel syndrome (IBS) patients and healthy individuals and showed that inflammatory mechanisms leading to IBS-like symptoms in UC may be different from the mechanisms leading to IBS., Background Inflammatory mechanisms of ulcerative colitis (UC) and irritable bowel syndrome (IBS) may overlap or are part of different spectrums. However, potential links between inflammation and IBS-like symptoms in these patient groups are still unclear. The aim of this study was to determine if the systemic inflammatory protein (SIP) profiles differ between UC patients, with presence of inflammation or in remission with or without IBS-like symptoms, and IBS patients. Methods Serum from patients with active UC (UCA), UC patients in remission with or without IBS-like symptoms (UCR + IBS, UCR-IBS), IBS patients (IBS), and healthy subjects (HS) was analyzed using the ProSeek Multiplex Inflammation kit, which detects 92 proteins. Results The exploratory cohort consisted of 166 subjects (UCA, n = 40; UCR-IBS, n = 45; UCR + IBS, n = 20; IBS, n = 40; HS, n = 21). Systemic inflammatory protein profiles separated UC from non-UC (HS and IBS) patients in multivariate analysis, revealing caspase 8, axin 1, sulfotransferase 1A1, and tumor necrosis factor superfamily member 14 as the variables most important to clustering. Although minor differences were detected between UCR + IBS and UCR-IBS, SIP profiles discriminated UCA from UCR, and interleukin (IL) 17C, IL17A, chemokine ligand 9, and transforming growth factor–α characterized active inflammation. SIP profiles weakly discriminated HS from IBS, although fibroblast growth factor 21 and IL6 serum levels were higher in IBS. Results were confirmed in a validation cohort (UCA, n = 15; UCR + IBS, n = 9; IBS, n = 14). Conclusions SIP profiles distinguish UC patients from IBS patients, irrespective of inflammation or IBS-like symptoms, suggesting that inflammatory mechanisms of the diseases are part of different spectrums.

Gut-directed hypnotherapy improves symptoms for patients with irritable bowel syndrome (IBS). Group hypnotherapy, as well as hypnotherapy administered by nurses, can increase treatment availability, but there are few comparisons between individual and group-based hypnotherapy.We aimed to evaluate and compare the effectiveness of nurse-administered hypnotherapy for IBS delivered individually or in groups.IBS patients were randomised to individual or group hypnotherapy (8 sessions, 12 weeks). The primary endpoint was changes in severity of IBS symptoms. A responder was defined as reduction of IBS severity scoring system (IBS-SSS) ≥50 points at the end of treatment compared to baseline. The effects on extracolonic and psychological symptoms, and quality of life were also assessed. Symptoms were also followed up 6 months after treatment start.A total of 119 patients were randomised (61 individual, 58 group hypnotherapy). Patients reported improvements in IBS symptoms (IBS-SSS) (individual: 332 (273-401) (median, IQR), versus 216 (140-308), (p 0.0001), group: 315 (239-382), versus 217 (149-314), (p 0.0001)), with no differences between the groups (p = 0.16). Extracolonic symptoms, psychological symptoms and quality of life also improved, without clear differences between the groups. Sixty-nine percent of the individual hypnotherapy patients were responders after treatment versus 57% of the group hypnotherapy patients (p = 0.25). Symptom improvements were also seen at follow-up.Nurse-administered gut-directed hypnotherapy, delivered individually or in groups, relieves IBS symptoms, improves psychological symptoms and quality of life. Group hypnotherapy can be an efficacious alternative, enabling more patients to benefit from the treatment (ClinicalTrials.gov ID no of study: NCT03432078).

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.

Somatization, defined as the presence of multiple somatic symptoms, frequently occurs in irritable bowel syndrome (IBS) and may constitute the clinical manifestation of a neurobiological sensitization process. Brain imaging data was acquired with T1 weighted 3 tesla MRI, and gray matter morphometry were analyzed using FreeSurfer. We investigated differences in networks of structural covariance, based on graph analysis, between regional gray matter volumes in IBS-related brain regions between IBS patients with high and low somatization levels, and compared them to healthy controls (HCs). When comparing IBS low somatization (N = 31), IBS high somatization (N = 35), and HCs (N = 31), we found: (1) higher centrality and neighbourhood connectivity of prefrontal cortex subregions in IBS high somatization compared to healthy controls; (2) higher centrality of left cerebellum in IBS low somatization compared to both IBS high somatization and healthy controls; (3) higher centrality of the anterior insula in healthy controls compared to both IBS groups, and in IBS low compared to IBS high somatization. The altered structural covariance of prefrontal cortex and anterior insula in IBS high somatization implicates that prefrontal processes may be more important than insular in the neurobiological sensitization process associated with IBS high somatization. ispartof: BRAIN SCIENCES vol:11 issue:12 ispartof: location:Switzerland status: published

Visceral hypersensitivity is an important pathophysiologic mechanism in irritable bowel syndrome (IBS). We compared 2 barostat distension protocols and their ability to distinguish between IBS patients and healthy controls, identify subjects with rectal hypersensitivity, and their associations with gastrointestinal symptom severity.We retrospectively reviewed all patients at our unit that had undergone barostat investigations 2002-2014. Protocol 1 (n = 369) used phasic isobaric distensions with stepwise increments in pressure and protocol 2 (n = 153) used pressure controlled ramp inflations. Both protocols terminated when subjects reported pain or maximum pressure was reached. Thresholds for first sensation, urgency, discomfort and pain were established. Age- and gender-matched controls were used for comparison. The gastrointestinal symptom rating scale-IBS, and the hospital anxiety and depression scale were used for symptom reports.A significantly higher proportion of patients was classified as having hypersensitivity in protocol 1 vs protocol 2 for all thresholds (Our study indicates that a rectal barostat protocol using phasic isobaric distensions with stepwise pressure increments is more sensitive in IBS patients with respect to identifying subjects with rectal hypersensitivity and a link with IBS symptoms.