| 1. |
- Eijsbouts, C., et al.
(författare)
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Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders
- 2021
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53:11, s. 1543-1552
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Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS. © 2021, The Author(s).
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| 2. |
- Boeckxstaens, G. E., et al.
(författare)
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Phenotyping of subjects for large scale studies on patients with IBS
- 2016
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 28:8, s. 1134-1147
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Tidskriftsartikel (refereegranskat)abstract
- Background: Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a ‘large’ pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. Purpose: The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu). © 2016 John Wiley & Sons Ltd
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| 3. |
- Simrén, Magnus, 1966, et al.
(författare)
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Visceral hypersensitivity is associated with GI symptom severity in functional GI disorders: consistent findings from five different patient cohorts
- 2018
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 67:2, s. 255-262
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Tidskriftsartikel (refereegranskat)abstract
- Objective Our aim was to evaluate the association between visceral hypersensitivity and GI symptom severity in large cohorts of patients with functional GI disorder (FGID) and to adjust for psychological factors and general tendency to report symptoms. Design We included five cohorts of patients with FGIDs (IBS or functional dyspepsia; n=1144), who had undergone visceral sensitivity testing using balloon distensions (gastric fundus, descending colon or rectum) and completed questionnaires to assess GI symptom severity, non-GI somatic symptoms, anxiety and depression. Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds. GI symptom severity was compared between sensitivity tertiles in each cohort and corrected for somatisation, and anxiety and depression. Results In all five cohorts, GI symptom severity increased gradually with increasing visceral sensitivity, with significant differences in GI symptom severity between the sensitivity tertiles (p<0.0001), with small to medium effect sizes (partial eta(2): 0.047-0.11). The differences between sensitivity tertiles remained significant in all cohorts after correction for anxiety and depression, and also after correction for non-GI somatic symptom reporting in all of the cohorts (p<0.05). Conclusions A gradual increase in GI symptom severity with increasing GI sensitivity was demonstrated in IBS and functional dyspepsia, which was consistent across several large patient groups from different countries, different methods to assess sensitivity and assessments in different parts of the GI tract. This association was independent of tendency to report symptoms or anxiety/depression comorbidity. These findings confirm that visceral hypersensitivity is a contributor to GI symptom generation in FGIDs.
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| 4. |
- Aguilera-Lizarraga, J., et al.
(författare)
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Expression of immune-related genes in rectum and colon descendens of Irritable Bowel Syndrome patients is unrelated to clinical symptoms
- 2019
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 31:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mucosal immune activation has been postulated to play an important role in the pathogenesis of irritable bowel syndrome (IBS). However, data are conflicting and often based on small patient cohorts. Here, we aimed to evaluate the gene expression of a large set of immune-related genes in mucosal biopsies from IBS patients and healthy volunteers (HV). Methods: A total of 171 IBS patients and 127 HV were included in the study. Rectum biopsies were collected from a cohort of 70 HV and 77 IBS patients (Rome III) and colon descendens biopsies from another cohort of 57 HV and 94 IBS patients (Rome II). Gene expression was assessed using OpenArray technology, and validated questionnaires were used to evaluate clinical characteristics (GI symptoms, somatization, anxiety, and depression). Key Results: A subset of IBS patients (33%) with increased immune activation in the colon descendens was identified using multivariate analysis and displayed increased gene expression of IL1B (3-fold change), prostaglandin synthase PTGS2 (2.1-fold change), and the G-protein-coupled receptor MRGPRX2 (10.7-fold change). Clinical characteristics in this subgroup were however similar to the rest of the patient cohort. Analysis of rectal biopsies failed to identify such subgroup of “immuno-active” IBS patients in the other patient cohort. Conclusion: A subset of IBS patients reveals evidence of immune activation in the colon descendens, but not in the rectum; however, gene expression is unrelated to clinical symptoms. To what extent this subgroup might however respond to anti-inflammatory therapy remains to be investigated. © 2019 John Wiley & Sons Ltd
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| 5. |
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| 6. |
- Nijs, Jo, et al.
(författare)
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Nutritional intervention in chronic pain: an innovative way of targeting central nervous system sensitization?
- 2020
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Ingår i: Expert Opinion on Therapeutic Targets. - : Informa UK Limited. - 1472-8222 .- 1744-7631. ; 24:8, s. 793-803
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Few treatment programs for chronic pain nowadays take a dietary pattern or adipose status into account. Areas covered An important role of neuroinflammation in chronic pain is now well established, at least in part due to increased central nervous system glial activation. Based on preclinical studies, it is postulated that the interaction between nutrition and central sensitization is mediated via bidirectional gut-brain interactions. This model of diet-induced neuroinflammation and consequent central sensitization generates a rationale for developing innovative treatments for patients with chronic pain. Methods: An umbrella approach to cover the authors' expert opinion within an evidence-based viewpoint. Expert opinion A low-saturated fat and low-added sugar dietary pattern potentially decreases oxidative stress, preventing Toll-like receptor activation and subsequent glial activation. A low-saturated fat and low-added sugar diet might also prevent afferent vagal nerve fibers sensing the pro-inflammatory mediators that come along with a high-(saturated) fat or energy-dense dietary pattern, thereby preventing them to signal peripheral inflammatory status to the brain. In addition, the gut microbiota produces polyamines, which hold the capacity to excite N-methyl-D-aspartate receptors, an essential component of the central nervous system sensitization. Hence, a diet reducing polyamine production by the gut microbiota requires exploration as a therapeutic target for cancer-related and non-cancer chronic pain.
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| 7. |
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| 8. |
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| 9. |
- Böhn, Lena, et al.
(författare)
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A randomized double-blind placebo-controlled crossover pilot study: Acute effects of the enzyme alpha-galactosidase on gastrointestinal symptoms in irritable bowel syndrome patients
- 2021
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 33:7
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Tidskriftsartikel (refereegranskat)abstract
- Background Postprandial symptoms presumably related to intestinal gas production are common in patients with irritable bowel syndrome (IBS). The aim of the study was to assess if oral alpha-galactosidase is superior to placebo in reducing gastrointestinal (GI) symptoms and intestinal gas production after ingestion of carbohydrate-rich meals in adult patients with IBS. Methods We studied the effect of 1200 GaIU/meal alpha-galactosidase (Nogasin(R)) or placebo capsules on GI symptoms in patients with IBS after three standardized, meals high in oligosaccharides, in a randomized, double-blind, crossover study. The intensity of eight GI symptoms was rated, and breath hydrogen and methane were measured every 30 min during 7.5 h. The severity of GI symptoms the following morning was assessed and compared with baseline.S Key Results Twenty adult patients with IBS (19 females), mean age 49 years (range 22-75 years), were included. All test meals were well tolerated but induced a gradual increase in GI symptom severity. Neither GI symptom ratings over time, nor hydrogen and methane concentrations differed between the days with alpha-galactosidase or placebo. The severity of abdominal pain and bloating was lower the following morning, but with no differences between alpha-galactosidase and placebo. Conclusions & Inferences The use of alpha-galactosidase together with meals high in oligosaccharides was in this pilot study not superior to placebo in reducing postprandial GI symptoms or the concentration of hydrogen and methane in expired air in IBS.
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| 10. |
- Clevers, Egbert, et al.
(författare)
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Adherence to diet low in fermentable carbohydrates and traditional diet for irritable bowel syndrome
- 2020
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Ingår i: Nutrition. - : Elsevier BV. - 0899-9007. ; 73
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Dietary interventions in irritable bowel syndrome (IBS) include a traditional IBS diet following the guidelines from the National Institute for Health and Clinical Excellence and a diet low in fermentable oligo-, di-, monosaccharides and polyols (FODMAPs). The aim of this study was to evaluate the adherence to these diets, food groups difficult to replace, and dietary determinants of symptom improvement. Methods: Sixty-six patients with IBS were randomized to a 4-wk low FODMAP or traditional IBS diet. Participants completed 4-d diet diaries before and during the intervention and reported symptoms on the IBS severity scoring system. We described adherence to the diets on the food group and product level and investigated the association between adherence and symptom improvement. Results: Adherence to the low FODMAP diet was good and consistent: All participants had a comparable shift in the diet's principal components compatible with the guidelines. Most high FODMAP products were well replaced with low FODMAP equivalents. However, total energy intake fell by 25%, mainly owing to a 69% decreased intake of snacks (P < 0.001). The traditional IBS diet did not shift the diet's principal components, and despite the guidelines, consumption of coffee and alcoholic beverages remained rather high (>50% of baseline). Total energy intake fell by 11% (P = 0.15). For both diets, there was a trend toward an association between adherence and symptom improvement (P < 0.10). Conclusion: In both the low FODMAP and traditional IBS diet, certain food groups were difficult to replace. Because adherence may predict symptom improvement, close dietary guidance might enhance the efficacy of both diets. © 2020 Elsevier Inc.
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| 11. |
- Clevers, Egbert, et al.
(författare)
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Development of Irritable Bowel Syndrome Features Over a 5-year Period
- 2018
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 16:8
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Tidskriftsartikel (refereegranskat)abstract
- 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 < .05) but other features of IBS were not. 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.
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| 12. |
- Clevers, Egbert, et al.
(författare)
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Factor Analysis Defines Distinct Upper and Lower Gastrointestinal Symptom Groups Compatible With Rome IV Criteria in a Population-based Study
- 2018
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 16:8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: The Rome IV criteria define functional gastrointestinal (GI) disorders by specific combinations of symptoms. It is possible to empirically evaluate these symptom combinations by factor analysis (a statistical procedure that groups variables that correlate). However, this analysis has not been performed for the Rome IV criteria, and factor analyses based on the previous versions of the Rome criteria did not use population-based data. We therefore investigated symptom grouping by the Rome IV questionnaire using factor analysis of a population-based sample. METHODS: The Rome IV questionnaire was completed online in English by 5931 respondents from the United Kingdom, United States, and Canada (49% female, age range, 18-92 years). We performed an exploratory factor analysis on the Rome IV questions. Next, we performed a confirmatory factor analysis to compare the exploratory factor result to that of the Rome IV criteria. RESULTS: The exploratory factor analysis identified 8 factors that accounted for 45% of the variance in response: constipation, diarrhea, irritable bowel syndrome, abdominal pain, heartburn, nausea or vomiting, globus, and other upper GI symptoms. Most factors corresponded to distinct functional GI disorders defined by the Rome IV criteria-exceptions included abdominal pain and upper GI symptoms. In confirmatory factor analysis, the exploratory model fitted slightly better than that based on the Rome IV criteria (root mean square error of approximation, 0.063 vs 0.077). CONCLUSIONS: We used factor analysis to identify distinct upper and lower GI symptom groups that are compatible with the Rome IV criteria. Our findings support the use of the Rome IV criteria in research and clinical practice as a basis for development of diagnostics and management of patients.
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| 13. |
- Clevers, Egbert, et al.
(författare)
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Food-symptom diaries can generate personalized lifestyle advice for managing gastrointestinal symptoms: A pilot study
- 2020
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 32:8
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Tidskriftsartikel (refereegranskat)abstract
- Background Gastrointestinal (GI) symptoms have a heterogeneous pathophysiology. Yet, clinical management uses group-level strategies. There is a need for studies exploring personalized management options in patients with GI symptoms. From diaries of GI symptoms, food intake, and psychological distress, we extracted and validated personalized lifestyle advice. Secondly, we investigated group-level GI symptom triggers using meta-analysis. Methods We collected 209 diaries of GI symptoms, food intake, and psychological distress, coming from 3 cohorts of patients with GI symptoms (n = 20, 26, and 163, median lengths 24, 17, and 38 days). Diaries were split into training and test data, analyzed, and the triggers emerging from the training data were tested in the test data. In addition, we did a random effects meta-analysis on the full data to establish the most common GI symptom triggers. Key Results Analysis of the training data allowed us to predict symptom triggers in the test data (r = 0.27, P < .001), especially in the subset of patients with a strong global association between lifestyle factors and symptoms (r = 0.45, P < .001). Low exposure to these triggers in the test data was associated with symptom reduction (P = .043). Meta-analysis showed that caloric intake in the late evening or night predicted an increase in GI symptoms, especially bloating. Several food-symptom associations were found, whereas psychological distress did not clearly lead to more severe GI symptoms. Conclusions & Inferences Diaries of GI symptoms, food intake, and psychological distress can lead to meaningful personalized lifestyle advice in subsets of patients.
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| 14. |
- Clevers, Egbert, et al.
(författare)
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Gastrointestinal symptoms in office workers are predicted by psychological distress and short sleep duration
- 2020
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Ingår i: Journal of Psychosomatic Research. - : Elsevier BV. - 0022-3999. ; 138
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Gastrointestinal (GI) symptoms can be triggered by several lifestyle factors, including psychological distress, short sleep duration, and diet. It is poorly known which physiological mechanisms are involved, but the autonomic nervous system (as a key mediator of the stress response) is a likely candidate. We aimed to investigate the associations between selected lifestyle factors, measures of stress physiology, and GI symptoms. Methods: This is a longitudinal study of 1002 office employees (52% male, mean age 39 +/- 10 years), who were asked to report their GI symptoms, psychological distress, sleep times, and intake of caffeine, alcohol, and soft drinks for 5 days. Skin conductance, heart rate / variability, and acceleration were automatically recorded using wearable sensors. 850 participants from this study were eligible for analysis. We computed within-person correlations between the variables and used mediation analysis to test causal models. Results: Sleep duration(rho = -0.12, p < 0.001) and psychological distress (rho = 0.19, p < 0.001) were significantly though weakly associated with GI symptoms. The physiological variables were not or weakly associated with GI symptoms in this study. The association between sleep duration and GI symptoms was largely mediated by psychological distress (61%). Conclusions: Short sleep and psychological distress predict GI symptoms in office workers. Further research is needed to unravel the physiological mechanisms mediate this association.
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| 15. |
- Clevers, Egbert, et al.
(författare)
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Health problems associated with irritable bowel syndrome: analysis of a primary care registry
- 2018
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Ingår i: Alimentary Pharmacology & Therapeutics. - : Wiley. - 0269-2813. ; 47:10, s. 1349-1357
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Tidskriftsartikel (refereegranskat)abstract
- 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=13701) 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.
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| 16. |
- Clevers, Egbert, et al.
(författare)
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Relations between food intake, psychological distress, and gastrointestinal symptoms: A diary study
- 2019
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Ingår i: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 7:7, s. 965-973
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastrointestinal symptoms can be triggered by food intake and psychological distress, but individual-level research on food-symptom and stress-symptom associations is scarce. Objective: We aimed to identify associations between food intake, psychological distress and gastrointestinal symptoms, and their implications for personalised clinical management. Methods: Through the mobile phone application mySymptoms, 163 users kept, for a median of five weeks, a diary of food intake, psychological distress and gastrointestinal symptoms. We quantified associations between these on the individual level. The presence of individual-level associations was compared over latent classes of daily symptom patterns. Results: Various gastrointestinal symptoms had demonstrable food-symptom associations (heartburn: 73%, discomfort: 67%, diarrhoea: 57%, bloating: 53%, and gas: 48%). Food-symptom associations for pain in the abdomen (33%) were concentrated in the latent class of individuals with pain in the morning (68%), rather than those with pain in the evening and night (27% and 10%, respectively, p < 0.001). Stress-symptom relations were also found, although only 18% of individuals reported psychological distress. Conclusion: Personal food-symptom and stress-symptom relations can be detected, and may translate into specific daily symptom patterns. A next step will be to let personal food-symptom and stress-symptom relations serve as the basis for personalised clinical management.
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| 17. |
- Colomier, Esther, 1995, et al.
(författare)
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Global prevalence and burden of meal-related abdominal pain
- 2022
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Ingår i: Bmc Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 18. |
- Colomier, Esther, 1995, et al.
(författare)
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Predictors of Symptom-Specific Treatment Response to Dietary Interventions in Irritable Bowel Syndrome
- 2022
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- (1) Background: Predictors of dietary treatment response in irritable bowel syndrome (IBS) remain understudied. We aimed to investigate predictors of symptom improvement during the low FODMAP and the traditional IBS diet for four weeks. (2) Methods: Baseline measures included faecal Dysbiosis Index, food diaries with daily energy and FODMAP intake, non-gastrointestinal (GI) somatic symptoms, GI-specific anxiety, and psychological distress. Outcomes were bloating, constipation, diarrhea, and pain symptom scores treated as continuous variables in linear mixed models. (3) Results: We included 33 and 34 patients on the low FODMAP and traditional IBS diet, respectively. Less severe dysbiosis and higher energy intake predicted better pain response to both diets. Less severe dysbiosis also predicted better constipation response to both diets. More severe psychological distress predicted worse bloating response to both diets. For the different outcomes, several differential predictors were identified, indicating that baseline factors could predict better improvement in one treatment arm, but worse improvement in the other treatment arm. (4) Conclusions: Psychological, nutritional, and microbial factors predict symptom improvement when following the low FODMAP and traditional IBS diet. Findings may help individualize dietary treatment in IBS. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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| 19. |
- Drossman, D. A., et al.
(författare)
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Neuromodulators for Functional Gastrointestinal Disorders (Disorders of Gut−Brain Interaction): A Rome Foundation Working Team Report
- 2018
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 154:4
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Central neuromodulators (antidepressants, antipsychotics, and other central nervous system−targeted medications) are increasingly used for treatment of functional gastrointestinal disorders (FGIDs), now recognized as disorders of gut−brain interaction. However, the available evidence and guidance for the use of central neuromodulators in these conditions is scanty and incomplete. In this Rome Foundation Working Team report, a multidisciplinary team summarized available research evidence and clinical experience to provide guidance and treatment recommendations. Methods: The working team summarized the literature on the pharmacology of central neuromodulators and their effects on gastrointestinal sensorimotor function and conducted an evidence-based review on their use for treating FGID syndromes. Because of the paucity of data for FGIDs, we included data for non-gastrointestinal painful disorders and specific symptoms of pain, nausea, and vomiting. This information was combined into a final document comprising a synthesis of available evidence and recommendations for clinical use guided by the research and clinical experience of the experts on the committee. Results: The evidence-based review on neuromodulators in FGID, restricted by the limited available controlled trials, was integrated with open-label studies and case series, along with the experience of experts to create recommendations using a consensus (Delphi) approach. Due to the diversity of conditions and complexity of treatment options, specific recommendations were generated for different FGIDs. However, some general recommendations include: (1) low to modest dosages of tricyclic antidepressants provide the most convincing evidence of benefit for treating chronic gastrointestinal pain and painful FGIDs and serotonin noradrenergic reuptake inhibitors can also be recommended, though further studies are needed; (2) augmentation, that is, adding a second treatment (adding quetiapine, aripiprazole, buspirone α2δ ligand agents) is recommended when a single medication is unsuccessful or produces side effects at higher dosages; (3) treatment should be continued for 6−12 months to potentially prevent relapse; and (4) implementation of successful treatment requires effective communication skills to improve patient acceptance and adherence, and to optimize the patient−provider relationship. Conclusions: Based on systematic and selectively focused review and the consensus of a multidisciplinary panel, we have provided summary information and guidelines for the use of central neuromodulators in the treatment of chronic gastrointestinal symptoms and FGIDs. Further studies are needed to confirm and refine these recommendations.
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| 20. |
- Farre, R., et al.
(författare)
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In Functional Dyspepsia, Hypersensitivity to Postprandial Distention Correlates With Meal-Related Symptom Severity
- 2013
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085. ; 145:3, s. 566-573
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Hypersensitivity to gastric distention, an important feature of functional dyspepsia, is assessed by stepwise balloon distention of the proximal stomach in fasting patients. However, symptoms of functional dyspepsia are often worse after a meal, so studies of postprandial balloon distentions might be more relevant. We compared the effects of fasting and postprandial stomach distention in patients with functional dyspepsia. METHODS: Twenty healthy controls and 62 patients with functional dyspepsia participated in a gastric barostat study at Leuven University Hospital with graded isobaric distentions before and after a liquid meal. On a separate day, all patients underwent a gastric emptying breath test with assessment of postprandial severity of 6 different dyspeptic symptoms scored at 15-minute intervals for 4 hours. For each symptom, a meal-related severity score was obtained by adding all scores; the cumulative symptom score (CSS) was obtained by adding individual symptom severity scores. RESULTS: In patients, but not in controls, postprandial sensitivity to balloon distention was significantly greater than fasting sensitivity. The CSS and individual symptom scores did not differ between patients with normal or hypersensitivity to fasting distention, but patients who were hypersensitive to postprandial distention had a significantly higher CSS, along with scores for postprandial fullness, bloating, and nausea (all P < .05). On multivariate analysis, hypersensitivity to postprandial distention was associated with hypersensitivity to fasting distention and with impaired accommodation to a meal. CONCLUSIONS: Postprandial, but not fasting, distention thresholds are related to the severity of meal-related symptoms in patients with functional dyspepsia.
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| 21. |
- Grinsvall, Cecilia, et al.
(författare)
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Altered Structural Covariance of Insula, Cerebellum and Prefrontal Cortex Is Associated with Somatic Symptom Levels in Irritable Bowel Syndrome (IBS)
- 2021
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Ingår i: Brain Sciences. - 2076-3425. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- 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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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| 22. |
- Grinsvall, Cecilia, et al.
(författare)
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Association between pain sensitivity and gray matter properties in the sensorimotor network in women with irritable bowel syndrome
- 2021
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 33:4
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Tidskriftsartikel (refereegranskat)abstract
- Background Enhanced perception of visceral stimuli is an important feature of Irritable Bowel Syndrome (IBS), but it is not known whether visceral sensitivity is associated with regional structural brain properties in IBS. Methods Structural brain magnetic resonance imaging data from 216 women with IBS and 138 healthy women were parcellated with FreeSurfer to define regional gray matter morphometry (volume, cortical thickness, surface area and mean curvature) in the sensorimotor network. General linear models were used to detect group differences between IBS and health. In a second set of 48 female IBS patients, pain threshold, pain intensity ratings during rectal balloon distension, and reported levels of abdominal pain and bloating were correlated with brain regions that showed differences between IBS and health in the first data set. Key Results Several statistically significant differences between IBS patients and healthy controls were found, mainly higher gray matter volume and cortical thickness in primary somatosensory cortex, secondary somatosensory cortex, and subcortical regions, and lesser gray matter volume, surface area and cortical thickness in posterior insula and superior frontal gyrus. Pain intensity ratings during rectal distension were associated with left primary somatosensory cortical thickness, and pain threshold was associated with right nucleus accumbens volume. Conclusions and Inferences Regional gray matter differences in sensorimotor network are associated with visceral sensitivity and may represent neuroplastic changes in female IBS patients.
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| 23. |
- Grinsvall, Cecilia, et al.
(författare)
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Psychological factors selectively upregulate rectal pain perception in hypersensitive patients with irritable bowel syndrome.
- 2015
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Ingår i: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 27:12, s. 1772-82
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Tidskriftsartikel (refereegranskat)abstract
- Visceral hypersensitivity and psychological symptoms are frequent features in irritable bowel syndrome (IBS). Exploring mechanistic pathways leading to visceral hypersensitivity is of importance to direct future studies and treatment options. In this study, we evaluated the contribution of psychological factors to the perception of painful and non-painful rectal sensations in hyper- vs normosensitive IBS patients.
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| 24. |
- Grinsvall, Cecilia, et al.
(författare)
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Relationships between psychological state, abuse, somatization and visceral pain sensitivity in irritable bowel syndrome
- 2018
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Ingår i: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 6:2, s. 300-309
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Psychological states may interfere with visceral sensitivity. Here we investigate associations between psychosocial factors and visceral sensitivity in irritable bowel syndrome (IBS). Methods: Two IBS patient cohorts (Cohort 1: n = 231, Rome II; Cohort 2: n = 141, Rome III) underwent rectal barostat testing, and completed questionnaires for anxiety, depression, somatization, and abuse. The associations between questionnaire measures and visceral sensitivity parameters were analyzed in three-step general linear models (step1: demographic and abuse variables; step 2: anxiety and depression; step 3: somatization). Results: Cohort 1. Pain threshold was positively associated with age and female gender, and negatively with adult sexual abuse and somatization. Pain referral area was negatively associated with age and positively with somatization and GI-specific anxiety, the latter effect mediated by somatization. Cohort 2. Pain threshold was positively associated with age and male gender, and negatively with adult sexual abuse. Pain intensity ratings were positively associated with somatization, female gender and depression, the latter effect mediated by somatization. Conclusion: Somatization is associated with most visceral sensitivity parameters, and mediates the effect of some psychological factors on visceral sensitivity. It may reflect a psychobiological sensitization process driving symptom generation in IBS. In addition, abuse history was found to independently affect some visceral sensitivity parameters.
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| 25. |
- Gunterberg, Veronica, et al.
(författare)
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Autonomic nervous system function predicts the inflammatory response over three years in newly diagnosed ulcerative colitis patients
- 2016
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 28:11, s. 1655-1662
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe autonomic nervous system (ANS) modulates intestinal inflammation in animal models. Human evidence confirming such modulating influence is limited. We aimed to investigate whether ANS function is associated with inflammatory parameters at disease onset, and whether it predicts the evolution of inflammation in patients with ulcerative colitis (UC). MethodsWe prospectively monitored 51 patients from onset of UC for 3 years. Upon remission of the onset flare, ANS activity was assessed by heart rate variability analysis and compared with healthy controls. Inflammatory parameters in blood, stool, and colonic biopsies obtained at onset and during follow-up visits were analyzed. Generalized linear models were used to test cross-sectional associations between ANS activity and inflammatory parameters at onset; linear mixed models were used to test whether ANS function at onset predicted the evolution of inflammation over the following 3 years. Key ResultsSympathovagal balance was different in UC patients compared to healthy controls, and cross-sectional associated with higher levels of systemic (erythrocyte sedimentation rate [ESR], CRP, TNF-, IFN-) and mucosal inflammation (interleukin-8, IFN-) at onset. Conversely, a negative cross-sectional association with parasympathetic activity was found for ESR & TNF-. Longitudinally, parasympathetic activity at onset predicted systemic (ESR, WBC), but not mucosal inflammation during follow-up. Conclusions & InferencesThis study further strengthens the association between the ANS system and intestinal inflammation previously found in animal models and recently in patients with inflammatory bowel disease. These results may have important implications for the pathogenesis and treatment of UC.
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| 26. |
- Janssen, P., et al.
(författare)
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The Relation Between Symptom Improvement and Gastric Emptying in the Treatment of Diabetic and Idiopathic Gastroparesis
- 2013
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270. ; 108:9, s. 1382-1391
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The relationship between symptom improvement (SI) and acceleration of gastric emptying (GE) for different drugs used in the treatment of idiopathic and diabetic gastroparesis is uncertain. In this paper we examined the study-specific correlations between SI and GE, and we performed a meta-regression analysis of the association across multiple studies. METHODS: The MEDLINE database (1,946 to present) was searched, and only controlled trials or trials with an established effective comparator that compared both SI and GE were included. RESULTS: Studies were identified for metoclopramide (n = 6), domperidone (n = 6), cisapride (n = 14), erythromycin (n = 3), botulinum toxin (n = 2), and levosulpiride (n = 3). Even though most drugs concomitantly improved symptoms and accelerated GE, no study reported a significant correlation between SI and GE. Moreover, a correlation analysis over all studies using meta-regression did not show a significant relationship between SI and GE. Our findings need to be qualified by inconsistencies in study methods, which is a limitation but also suggests that our findings are robust to methodological factors. CONCLUSIONS: In this review, no evidence of a relationship between SI and GE was identified for different drugs used for the treatment of gastroparesis. This finding questions the use of GE measurement to direct drug development for gastroparesis.
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| 27. |
- Kano, M., et al.
(författare)
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Resting state functional connectivity of the pain matrix and default mode network in irritable bowel syndrome: a graph theoretical analysis
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) is a functional disorder of brain-gut interactions. Differential brain responses to rectal distention between IBS and healthy controls (HCs) have been demonstrated, particularly in the pain matrix and the default mode network. This study aims to compare resting-state functional properties of these networks between IBS patients and HCs using graph analysis in two independent cohorts. We used a weighted graph analysis of the adjacency matrix based on partial correlations between time series in the different regions in each subject to determine subject specific graph measures. These graph measures were normalized by values obtained in equivalent random networks. We did not find any significant differences between IBS patients and controls in global normalized graph measures, hubs, or modularity structure of the pain matrix and the DMN in any of our two independent cohorts. Furthermore, we did not find consistent associations between these global network measures and IBS symptom severity or GI-specific anxiety but we found a significant difference in the relationship between measures of psychological distress (anxiety and/or depressive symptoms) and normalized characteristic path length. The responses of these networks to visceral stimulation rather than their organisation at rest may be primarily disturbed in IBS.
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| 28. |
- Melchior, Chloé, 1985, et al.
(författare)
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Relationship Between Abuse History and Gastrointestinal and Extraintestinal Symptom Severity in Irritable Bowel Syndrome
- 2022
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Ingår i: Psychosomatic Medicine. - 0033-3174. ; 84:9, s. 1021-1033
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Tidskriftsartikel (refereegranskat)abstract
- 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, R-2 = 0.43, and F = 22.330, R-2 = 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, R-2 = 0.28; F = 15.065, R-2 = 0.30; and F = 18.037, R-2 = 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.
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| 29. |
- Pohl, D., et al.
(författare)
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Functional Dyspepsia and Severity of Psychologic Symptoms Associate With Postprandial Symptoms in Patients With Irritable Bowel Syndrome
- 2018
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 16:11, s. 1745-1753
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: In a prospective study of patients with IBS, we found those with FD to have increased GI symptoms before and after a liquidmeal 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.
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| 30. |
- Simrén, Magnus, 1966, et al.
(författare)
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Cumulative Effects of Psychologic Distress, Visceral Hypersensitivity, and Abnormal Transit on Patient-reported Outcomes in Irritable Bowel Syndrome
- 2019
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085. ; 157:2, s. 391-402
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Little is known about the link between pathophysiologic factors and symptoms of irritable bowel syndrome (IBS), or whether these factors have cumulative effects on patient-reported outcomes (PROs). We investigated whether pathophysiologic alterations associated with IBS have cumulative or independent effects on PROs. METHODS: We performed a retrospective analysis of data from 3 cohorts of patients with IBS (n = 407; 74% female; mean age, 36 +/- 12 years), based on Rome II or Rome III criteria, seen at a specialized unit for functional gastrointestinal disorders in Sweden from 2002 through 2014. All patients underwent assessments of colonic transit time (radiopaque markers); compliance, allodynia, and hyperalgesia (rectal barostat); anxiety and depression (Hospital Anxiety and Depression scale), as pathophysiologic factors. Dysfunction was defined by available normal values. PROs included IBS symptom severity, somatic symptom severity, and disease-specific quality of life. RESULTS: Allodynia was observed in 36% of patients, hyperalgesia in 22%, accelerated colonic transit in 18%, delayed transit in 7%, anxiety in 52%, and depression in 24%: each of these factors was associated with severity of at least 1 symptom of IBS. Rectal compliance was not associated with more severe symptoms of IBS. At least 3 pathophysiologic factors were present in 20% of patients, 2 in 30%, 1 in 31%, and none in 18%. With increasing number of pathophysiologic abnormalities, there was a gradual increase in IBS symptom severity (P < .0001) and somatic symptom severity (P < .0001), and a gradual reduction in quality of life (P < .0001). CONCLUSION: Visceral hypersensitivity, including allodynia and hyperalgesia, abnormal colonic transit, and psychologic factors are all associated with IBS symptoms. These factors have a cumulative effect on gastrointestinal and non-gastrointestinal symptoms, as well as on quality of life, in patients with IBS and are therefore relevant treatment targets.
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| 31. |
- Tack, J., et al.
(författare)
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Plausibility criteria for putative pathophysiological mechanisms in functional gastrointestinal disorders: a consensus of experts
- 2018
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 67:8, s. 1425-1433
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims The functional gastrointestinal disorders (FGIDs) are extremely common conditions associated with a considerable personal, social and health economic burden. Managing FGIDs in clinical practice is challenging because of the uncertainty of symptom-based diagnosis, the high frequency of overlap between these conditions and the limited efficacy of available therapies. It has often been argued that successful drug development and management of FGIDs requires knowledge of the underlying pathophysiology. Numerous and highly variable candidate pathophysiological mechanisms have been implicated in the generation of FGID symptoms, but there is no current consensus on how to best define the relevance of these disturbances. Methods A group of international experts on FGIDs developed plausibility criteria that should be fulfilled by relevant pathophysiological mechanisms in FGIDs. Results Five criteria are proposed: (1) the presence of the abnormality in a subset of patients, (2) temporal association between proposed mechanism and symptom(s), (3) correlation between the level of impairment of the mechanism and symptom(s), (4) induction of the symptom(s) by provoking the pathophysiological abnormality in healthy subjects and (5) treatment response by a therapy specifically correcting the underlying disorder or congruent natural history of symptoms and dysfunction in the absence of specific therapy. Based on strength of evidence for these five criteria according to the Grading of Recommendations Assessment, Development and Evaluation system, a plausibility score can be calculated for each mechanism. Conclusion Evaluation of the strength of evidence for candidate pathophysiological abnormalities fulfilling these five plausibility criteria will help to identify the most relevant mechanisms to target for novel diagnostic approaches and for the development of new therapies.
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| 32. |
- Törnblom, Hans, 1966, et al.
(författare)
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Colonic Transit Time and IBS Symptoms: What's the Link
- 2012
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 107:5, s. 754-760
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The relevance of colonic transit alterations for the overall symptom pattern in irritable bowel syndrome (IBS) is incompletely understood. The aim of this study was to assess the total and segmental colonic transit time (CTT) and their relationship to symptoms and subgroups in a large sample of IBS patients. METHODS: Total and segmental CTT was assessed using radiopaque markers in 359 patients with IBS (279 females). These results were compared with existing normal values for healthy men and women without gastrointestinal (GI) symptoms. Stool frequency and consistency (Bristol Stool Form (BSF) scale), and the perceived severity of three GI symptoms (bloating, flatulence, and abdominal pain) were noted in a daily diary during the measurement week. Patients could be classified by the BSF scale characteristics into Rome III subtypes (n = 338), or by use of the Rome II modular questionnaire into Rome II subtypes (n = 143). RESULTS: CTT was normal in 287 patients (80%), whereas 53 (15%) had accelerated and 19 (5%) had delayed CTT. Transit abnormalities in relation to gender-specific reference values were more common in males (30.0%) than in females (17.2%; P<0.05). IBS subgrouping according to Rome III (P<0.0001) and Rome II criteria (P<0.001) was associated with the presence of abnormal CTT. Stool form (r=-0.40; P<0.0001) and stool frequency (r=-0.30; P<0.0001) were moderately and negatively correlated to total CTT. No correlations of clinical significance were found between transit data and the three GI symptoms. CONCLUSIONS: Total and segmental colonic transit alterations are of importance for the abnormal bowel habit seen in men and women with IBS, but of no or minor importance for other IBS symptoms.
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