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Introduction: Patients with irritable bowel syndrome (IBS) often attribute the onset or worsening of gastrointestinal symptoms to intake of food. Hence, to alleviate symptoms, patients with IBS may avoid triggering foods, potentially impacting their dietary intake and diet quality. This study aimed to compare the habitual diet intake and quality of patients with IBS with controls and to explore the association between dietary habits and symptoms in patients with IBS., Methods: Patients with IBS were included in 4 clinical studies reporting habitual dietary intakes at baseline. Age- and sex-matched controls representing the general population were derived from the Swedish population-based Riksmaten study. Dietary intakes were assessed using 4-day food diaries. Diet quality was measured using the diet quality index-Swedish national dietary guidelines (DQI-SNR), and diet diversity was scored based on the variety of food groups consumed., Results: The study included 646 patients with IBS and 646 controls (38 ± 14 years, 77% female). Both groups adhered to Nordic nutrition recommendations for macronutrients, except patients consumed fewer carbohydrates. Patients reported eating less carbohydrates, coffee, and dairy products and more fats, lactose-free dairy products, and nuts and seeds compared with controls. Fewer patients had a good diet quality according to the DQI-SNR. In patients, symptom severity and gastrointestinal-specific anxiety were associated with reduced energy and carbohydrate intake, lower diet diversity, and worse diet quality. Poor diet quality was associated with younger age, more severe IBS symptoms, anxiety, and depression., Discussion: Patients with IBS exhibit different dietary patterns compared with controls, with poorer dietary habits linked to more severe symptoms. Understanding food-symptom associations may enhance the optimization and personalization of dietary management for patients with IBS., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: This study focused on defining the global prevalence of clinically relevant levels of psychological distress and somatic symptoms and the prevalence of coexistence between these symptoms and disorders of gut-brain interaction (DGBI). We also analyzed how clinically relevant psychological distress and somatic symptoms and coexistent DGBI are associated with health-related outcomes., Methods: We included a representative sample of 54,127 adult participants (49.1% women; mean age of 44.3 years) from 26 countries worldwide. Participants completed an Internet survey (the Rome Foundation Global Epidemiology Study) with validated self-report questionnaires., Results: Clinically relevant psychological distress and/or somatic symptom severity was reported by 37.5% of the sample. These participants had 4.45 times higher odds to have at least one DGBI than individuals without psychological distress and/or somatic symptoms. Compared with participants with psychological distress and/or somatic symptoms with vs without DGBI, participants with a DGBI reported increased healthcare and medication utilization (with OR from 1.6 to 2.8). Coexistent DGBI in participants with psychological distress and/or somatic symptoms was the variable most strongly associated with reduced mental (β = -0.77; confidence interval [-0.86 to -0.68]) and physical (β = -1.17; confidence interval [-1.24 to -1.10]) quality of life., Discussion: This global study shows that psychological distress, somatic symptoms, and DGBI are very common and frequently overlap. The coexistence between psychological distress/somatic symptoms and DGBI seems to be especially detrimental to quality of life and healthcare utilization. Individuals with psychological distress/somatic symptoms and DGBI coexistence seem to be a group vulnerable to psychosocial problems that should be studied further and would likely benefit from psychological/psychiatric interventions., (Copyright © 2023 by The American College of Gastroenterology.)

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

Introduction: Treatment options for irritable bowel syndrome (IBS) are limited, causing many patients to remain symptomatic. This study assessed the potential of human milk oligosaccharides (HMOs) to normalize bowel habits. Secondary outcomes included IBS severity and health-related quality of life., Methods: This multicenter, open-label trial recruited patients with IBS from 17 sites across the United States. Patients received daily orally administrated 5-g intervention of the HMOs 2'-fucosyllactose and lacto-N-neotetraose in a 4:1 mix. Bowel habits, IBS symptoms, and quality of life were assessed at baseline and every 4 weeks during the 12-week intervention., Results: A total of 317 patients (70.7% women; mean age of 44.0 years, range 18-93 years) received the trial product, and 245 patients completed the trial according to protocol. Patients had a significant improvement from baseline to 12 weeks in total percentage of bowel movements with abnormal stool consistency (mean and [95% confidence interval]: 90.7 [88.9-92.9] vs 57.2% [53.9-60.5], P < 0.0001), overall IBS Symptom Severity Score (323 [314-332] vs 144 [133-155], P < 0.0001) and health-rela,ted quality of life (50.4 [48.0-52.8] vs 74.6 [72.3-76.9], P < 0.0001). Improvement was similar across IBS subtypes. Symptoms improved most in the first 4 weeks of intervention. The most common side effects were mild gastrointestinal symptoms such as flatulence, abdominal pain and discomfort, and distension., Discussion: Supplementation with 2 selected HMOs improves IBS symptoms and quality of life without substantial side effects. These promising results suggest that this novel approach to IBS should be confirmed in a randomized, placebo-controlled trial.

Introduction: Gastrointestinal symptoms in irritable bowel syndrome (IBS) have been correlated with psychological factors using retrospective symptom assessment. However, real-time symptom assessment might reveal the interplay between abdominal and affective symptoms more reliably in a longitudinal perspective. The aim was to evaluate the association between stress and abdominal pain, using the Experience Sampling Method (ESM) as a real-time, repeated measurement method., Methods: Thirty-seven patients with IBS (26 women; mean age 36.7 years) and 36 healthy controls (HC; 24 women; mean age 31.1 years) completed an electronic ESM during 7 consecutive days. Abdominal pain and stress were scored on an 11-point Numeric Rating Scale at a maximum of 10 random moments each day., Results: Abdominal pain scores were 2.21 points higher in patients with IBS compared with those in HC (P < 0.001), whereas stress levels did not differ significantly (B: 0.250, P = 0.406). In IBS, a 1-point increase in stress was associated with, on average, 0.10 points increase in abdominal pain (P = 0.017). In HC, this was only 0.02 (P = 0.002). Stress levels at t = -1 were not a significant predictor for abdominal pain at t = 0 in both groups, and vice versa., Discussion: Our results demonstrate a positive association between real-time stress and abdominal pain scores and indicate a difference in response to stress and not a difference in experienced stress per se. Furthermore, an in-the-moment rather than a longitudinal association is suggested. This study underlines the importance of considering the individual flow of daily life and supports the use of real-time measurement when interpreting potential influencers of abdominal symptoms in IBS.

Objectives: Patients with irritable bowel syndrome (IBS) are more likely to be both absent from and impaired at work compared to non-IBS patients. We investigated the impact of IBS on work productivity and activity impairment and the relationship to disease specific and general health measures., Method: In total, 525 patients with IBS completed questionnaires assessing work productivity and activity impairment, IBS symptom severity, IBS-related quality of life and GI-specific anxiety. In addition, 155 of the patients completed questionnaires assessing severity of somatic symptoms, depression, anxiety and fatigue. Uni- and bivariate analyses were performed, as well as linear regression to determine factors independently associated with the work productivity and activity impairment measures., Results: Of employed patients, 24.3% reported absenteeism and 86.8% reported presenteeism because of their IBS. With increasing severity of IBS symptoms and GI-specific anxiety, higher degrees of work impairment were seen. Work productivity impairment in IBS was also associated with low quality of life. GI-specific anxiety was independently associated with absenteeism (R 2  = 0.23; p < 0.05), IBS-symptom severity and general fatigue with presenteeism (R 2  = 0.40; p < 0.05), IBS-symptom severity, general fatigue and GI-specific anxiety with overall work loss (R 2  = 0.50; p < 0.05), and IBS symptom severity and somatic symptoms with activity impairment (R 2  = 0.38; p < 0.05)., Conclusion: Work impairment is a substantial problem in patients with IBS. A combination of IBS and somatic symptom severity, fatigue and psychological factors influence patients' ability to be present, active and productive at work. Based on this, a multidimensional treatment approach for patients with IBS seems logical.

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

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

Objectives: Few treatments have been able to effectively manage pediatric irritable bowel syndrome (IBS). Internet-delivered cognitive behavior therapy (Internet-CBT) based on exposure for abdominal symptoms is effective for adult IBS. The objective of this study was to evaluate the efficacy of Internet-CBT based on behavioral exposure for adolescents with IBS., Methods: Adolescents with IBS fulfilling the Rome III criteria were randomized to either Internet-CBT or a wait-list control. The Internet-CBT was a 10-week intervention where the main component was exposure to IBS symptoms by reduction of avoidance of abdominal symptoms and instead stepwise provocation of symptoms. The primary outcome was total score on Gastrointestinal Symptoms Rating Scale for IBS (GSRS-IBS). Secondary outcomes included adolescent- and parent-rated quality of life and parent-rated gastrointestinal symptoms. Difference between groups was assessed from pretreatment to posttreatment and the Internet-CBT group was also evaluated at 6 months after treatment completion., Results: A total of 101 adolescents with IBS (13-17 years of age) were included in this study. Dropout rates were low (6%) and all randomized patients were included in intent-to-treat analyses based on mixed effects models. Analyses showed a significant larger pretreatment to posttreatment change on the primary outcome GSRS-IBS (B=-6.42, P=0.006, effect size Cohen's d=0.45, 95% confidence interval (0.12, 0.77)) and on almost all secondary outcomes for the Internet-CBT group compared with the control group. After 6 months, the results were stable or significantly improved., Conclusions: Internet-CBT based on exposure exercises for adolescents with IBS can effectively improve gastrointestinal symptoms and quality of life.

Objectives: Evidence suggests that patients with irritable bowel syndrome (IBS) have an altered cytokine profile, although it is unclear whether cytokines are linked with symptom severity. We aimed to determine whether global serum and mucosal cytokine profiles differ between IBS patients and healthy subjects and whether cytokines are associated with IBS symptoms., Methods: Serum from 144 IBS patients and 42 healthy subjects was analyzed for cytokine levels of interleukin (IL)-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, interferon (IFN)-γ, and tumor necrosis factor (TNF) by MSD MULTI-ARRAY. In total, 109 IBS and 36 healthy sigmoid colon biopsies were analyzed for mRNA expression of IL-8, IL-10, TNF, and FOXP3 by quantitative reverse transcription PCR. Multivariate discrimination analysis evaluated global cytokine profiles. Rectal sensitivity, oroanal transit time, and psychological and gastrointestinal symptom severity were also assessed., Results: Global cytokine profiles of IBS patients and healthy subjects overlapped, but cytokine levels varied more in IBS patients. Serum levels of IL-6 and IL-8 tended to be increased and levels of IFN-γ tended to be decreased in IBS patients. Mucosal mRNA expression of IL-10 and FOXP3 tended to be decreased in IBS patients. Within both the full study cohort and IBS patients alone, serum level of TNF was associated with looser stool pattern, while subjects with more widespread somatic symptoms had increased serum levels of IL-6. Although neither IBS bowel habit subgroups nor patients with possible post-infectious IBS were associated with distinct cytokine profiles, a small cluster of IBS patients with comparatively elevated immune markers was identified., Conclusions: Global cytokine profiles did not discriminate IBS patients from healthy subjects, but cytokine profiles were more varied among IBS patients than among healthy subjects, and a small subgroup of patients with enhanced immune activity was identified. Also, association of inflammatory cytokines with some clinical symptoms suggests that immune activation may be of importance in a subset of IBS patients.

Objectives: Gastroparesis is a well-known complication to diabetes mellitus (DM). Dietary advice is considered to be of importance to reduce gastrointestinal (GI) symptoms in patients with diabetic gastroparesis, but no randomized controlled trials exist. Our aim was to compare GI symptoms in insulin treated DM subjects with gastroparesis eating a diet with small particle size ("intervention diet") with the recommended diet for DM ("control diet")., Methods: 56 subjects with insulin treated DM and gastroparesis were randomized to the intervention diet or the control diet. The patients received dietary advice by a dietitian at 7 occasions during 20 weeks. GI symptom severity, nutrient intake and glycemic control were measured before and after the intervention., Results: A significantly greater reduction of the severity of the key gastroparetic symptoms-nausea/vomiting (P=0.01), postprandial fullness (P=0.02) and bloating (P=0.006)-were seen in patients who received the intervention diet compared with the control diet, and this was also true for regurgitation/heartburn (P=0.02), but not for abdominal pain. Anxiety was reduced after the intervention diet, but not after the control diet, whereas no effect on depression or quality of life was noted in any of the groups. A higher fat intake in the intervention group was noted, but otherwise no differences in body weight, HbA1c or nutrient intake were seen., Conclusions: A small particle diet improves the key symptoms of gastroparesis in patients with diabetes mellitus. (ClinicalTrials.gov NCT01557296).

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.

Objectives: The aim of the present pilot study was to evaluate the usefulness of a test meal containing lactulose in the non-invasive assessment of visceral sensitivity in irritable bowel syndrome (IBS), and to identify subsets of IBS patients based on gastrointestinal (GI) symptom generation., Methods: We included 43 patients with IBS (Rome III) and 29 healthy controls. The fasted subjects were served three test meals consisting of a 400-ml liquid breakfast alone or containing lactulose (15 or 25 g) in a double-blind crossover design. Seven GI symptoms, overall digestive comfort, and exhaled H2/CH4 were assessed at baseline and every 15 min during 4 h after meal intake. Anxiety and depression were assessed only at baseline. A mapping of the seven GI symptoms was done using a Principal Component Analysis (4 h mean area under the curve, AUC). Independently, a hierarchical cluster analysis was performed on the same parameters to identify GI symptom-based IBS clusters., Results: All three tests were well tolerated. The 25 g lactulose challenge enabled discrimination of IBS from healthy controls according to the symptom response. This challenge also enabled clustering of IBS subjects in two subgroups based mainly on bloating, distension, and discomfort symptoms (2,457 (2,043-2,872), 2,450 (1,910-2,990), 2,602 (2,126-3,079) vs. 537 (383-691), 619 (458-780), 643 (432-854); 4 h mean AUC; P<0.0001), overall digestive comfort (1807 (1318-2295) vs. 3350 (2942-3758); 4 h mean AUC; P<0.0001), and anxiety at baseline (9.2 (7.0-11.5) vs. 5.5 (4.2-6.9); Hospital Anxiety and Depression scale anxiety mean scores; P=0.003). This clustering was independent of the Rome III subtype and the amount of exhaled H2/CH4., Conclusions: The lactulose challenge test seems to be a promising tool to assess visceral sensitivity in IBS, and to subgroup IBS patients based on their symptom pattern.

Objectives: Despite the fact that food and diet are central issues, that concern patients with irritable bowel syndrome (IBS), the current understanding about the association between the intake of certain foods/food groups and the gastrointestinal (GI) symptom pattern, psychological symptoms, and quality of life is poor. The aim of this study was to determine which food groups and specific food items IBS patients report causing GI symptoms, and to investigate the association with GI and psychological symptoms and quality of life., Methods: We included 197 IBS patients (mean age 35 (18-72) years; 142 female subjects) who completed a food questionnaire in which they specified symptoms from 56 different food items or food groups relevant to food intolerance/allergy. The patients also completed questionnaires to assess depression and general anxiety (Hospital Anxiety and Depression), GI-specific anxiety (Visceral Sensitivity Index), IBS symptoms (IBS-Severity Scoring System), somatic symptoms (Patient Health Questionnaire-15), and quality of life (Irritable Bowel Syndrome Quality of Life Questionnaire)., Results: In all, 84% of the studied population reported symptoms related to at least one of the food items surveyed. Symptoms related to intake of food items with incompletely absorbed carbohydrates were noted in 138 (70%) patients; the most common were dairy products (49%), beans/lentils (36%), apple (28%), flour (24%), and plum (23%). Of these, 58% experienced GI symptoms from foods rich in biogenic amines, such as wine/beer (31%), salami (22%), and cheese (20%). Histamine-releasing foods, such as milk (43%), wine/beer (31%), and pork (21%), were also considered causes of symptoms in IBS patients. GI symptoms were also frequently reported after intake of fried and fatty foods (52%). With increasing IBS symptom severity, patients reported more food items responsible for their GI symptoms (P=0.004), and this was also found in patients with more severe somatic symptoms (P<0.0001). Women tended to report more food items causing symptoms than men (P=0.06). A high number of food items causing GI symptoms was also associated with reduced quality of life and this was significant for the following domains: sleep (r=-0.25; P=0.001), energy (r=-0.21; P=0.005), food (r=-0.29; P<0.001), social functioning (r=-0.23; P=0.001), and physical status (r=-0.16; P<0.05). However, the number of food items reported to provoke GI symptoms was unrelated to body mass index, age, IBS subtype, anxiety, depression, or GI-specific anxiety., Conclusions: The majority of IBS patients believe that certain food items are important triggers of their GI symptoms. This is especially true for foods containing carbohydrates and fat, and also may be relevant for histamine-releasing food items and foods rich in biogenic amines. Self-reported food intolerance is associated with high symptom burden and reduced quality of life.

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.

Objectives: Chromogranins (Cg) and secretogranins (Sg) are proteins ubiquitous in secretory cells of the enteric, endocrine, and immune systems, and may reflect activity of these systems. We therefore performed a hypothesis generating study to evaluate the association between fecal levels of CgA, CgB, SgII, and SgIII, with the clinical and pathophysiological phenotype of irritable bowel syndrome (IBS) patients., Methods: Analyses of CgA, CgB, SgII, SgIII, and calprotectin in fecal samples of 82 IBS patients and 29 healthy controls were performed. All IBS subjects completed validated questionnaires to assess gastrointestinal and psychological symptom severity, and underwent rectal barostat test and colonic transit time measurement., Results: IBS patients demonstrated higher levels of fecal CgA (P=0.009), SgII (P<0.001), and SgIII (P<0.001), but lower levels of CgB (P<0.001) compared with controls. SgII had good discriminative validity to positively identify IBS patients, with an area under the receiver operating characteristics (ROC) curve (AUROC) of 0.86 (95% confidence interval (CI): 0.78-0.94). SgIII and CgB both had fairly good discriminative validity to positively identify IBS patients, with an AUROC of 0.79 (95% CI: 0.71-0.87) and 0.78 (95% CI: 0.69-0.87), respectively. There were negative correlations between the colonic transit time and fecal levels of CgA (r=-0.53, P<0.001), SgII (r=-0.55, P<0.001), and SgIII (r=-0.28, P=0.03). Perceived abdominal pain was moderately associated with levels of CgA (r=0.32, P=0.004), SgII (r=0.31, P=0.006), and SgIII (r=0.24, P=0.04). Calprotectin levels were not associated with the levels of granins or with the clinical or pathophysiological phenotype of IBS patients., Conclusions: Fecal levels of Cg and Sg may be related to the underlying pathophysiology of IBS and of potential importance for symptoms of the patients. Granins also show promise to serve as future biomarkers of IBS. Further studies are needed to explore the potential role of granins in IBS patients.

Objectives: Gut-directed hypnotherapy has been found to be effective in irritable bowel syndrome (IBS). However, randomized, controlled studies are rare and few have been performed outside highly specialized research centers. The objective of this study was to study the effect of gut-directed hypnotherapy in IBS in different clinical settings outside the traditional research units., Methods: The study population included IBS patients refractory to standard management. In study 1, patients were randomized to receive gut-directed hypnotherapy (12 sessions, 1 h/week) in psychology private practices or supportive therapy, whereas patients were randomized to receive gut-directed hypnotherapy in a small county hospital or to serve as waiting list controls in study 2. Gastrointestinal symptom severity and quality of life were evaluated at baseline, at 3 months follow-up and after 1 year., Results: We randomized 138 IBS patients refractory to standard management, 90 in study 1 and 48 in study 2. In both the studies, IBS-related symptoms were improved at 3 months in the gut-directed hypnotherapy groups (P<0.05), but not in the control groups (ns). In study 1, a significantly greater improvement of IBS-related symptom severity could be detected in the gut-directed hypnotherapy group than in the control group (P<0.05), and a trend in the same direction was seen in study 2 (P=0.17). The results seen at 3 months were sustained up to 1 year., Conclusions: Gut-directed hypnotherapy is an effective treatment alternative for patients with refractory IBS, but the effectiveness is lower when the therapy is given outside the highly specialized research centers.

Objectives: Physical activity has been shown to be effective in the treatment of conditions, such as fibromyalgia and depression. Although these conditions are associated with irritable bowel syndrome (IBS), no study has assessed the effect of physical activity on gastrointestinal (GI) symptoms in IBS. The aim was to study the effect of physical activity on symptoms in IBS., Methods: We randomized 102 patients to a physical activity group and a control group. Patients of the physical activity group were instructed by a physiotherapist to increase their physical activity, and those of the control group were instructed to maintain their lifestyle. The primary end point was to assess the change in the IBS Severity Scoring System (IBS-SSS)., Results: A total of 38 (73.7% women, median age 38.5 (19-65) years) patients in the control group and 37 (75.7% women, median age 36 (18-65) years) patients in the physical activity group completed the study. There was a significant difference in the improvement in the IBS-SSS score between the physical activity group and the control group (-51 (-130 and 49) vs. -5 (-101 and 118), P=0.003). The proportion of patients with increased IBS symptom severity during the study was significantly larger in the control group than in the physical activity group., Conclusions: Increased physical activity improves GI symptoms in IBS. Physically active patients with IBS will face less symptom deterioration compared with physically inactive patients. Physical activity should be used as a primary treatment modality in IBS.

Objectives: Conflicting data exist on whether discontinuation of proton pump inhibitors (PPIs) is associated with rebound secretion of gastric acid., Methods: A total of 48 healthy Helicobacter pylori-negative volunteers (24 females) were randomized in a double-blinded manner to treatment with either pantoprazole 40 mg or placebo once daily for 28 days. Dyspeptic symptoms were registered daily using the Glasgow dyspepsia score (GDS) 2 weeks before, during, and 6 weeks after treatment. Plasma levels of gastrin and serum levels of chromogranin-A levels were measured before, during, and after treatment., Results: During the 2 weeks before treatment, the placebo group had a mean GDS of 0.20 + or - 0.7 compared with the pantoprazole group score of 0.54 + or - 1.3 (NS). No significant differences between the symptom severity scores of the two groups were shown during the treatment period. During the first week after discontinuation of treatment, the pantoprazole group had a mean symptom score of 5.7 + or - 11.7 vs. 0.74 + or - 2.6 in the placebo group (P<0.01). A total of 11 out of 25 (44%) subjects in the pantoprazole group developed dyspepsia compared with 2 out of 23 (9%) in the placebo group (P<0.01). During the second week of follow-up, the pantoprazole group had a mean symptom score of 1.6 + or - 3.4 compared with 0 + or - 0 in the placebo group (P<0.05). There were no significant differences in the mean symptom score for the pantoprazole group (1.1 + or - 0.6) compared with the placebo group (0.4 + or - 0.3) during the third week of follow-up. Symptom scores during the first week after treatment correlated with basal (P<0.01) and meal-stimulated (P<0.01) gastrin levels at the end of treatment., Conclusions: A 4-week course of pantoprazole seems to induce dyspeptic symptoms in previously asymptomatic healthy H. pylori-negative subjects. The correlation between symptom score and gastrin levels suggests that these symptoms are due to acid rebound hypersecretion and seem to be related to the degree of acid inhibition.

Objectives: Irritable bowel syndrome (IBS) has been found to be associated with low-grade immune activation in a subset of patients. We therefore investigated blood and colonic T-cell activity in IBS patients., Methods: Blood samples were initially obtained from 74 IBS patients and 30 controls. Supplementary blood samples, to confirm data, were taken from another cohort (26 patients and 14 controls). In addition, colonic biopsies were taken from a third cohort (11 patients and 10 controls). Peripheral blood and colonic mononuclear cells were stimulated with anti-CD3/CD28 antibodies. Proliferation, cytokine secretion, and T-cell phenotype were investigated. IBS symptom severity was assessed., Results: IBS patients displayed an activated phenotype with increased frequencies of blood T cells expressing CD69 and integrin beta7/HLA-DR. Anti-CD3/CD28-stimulated blood and colonic T cells from IBS patients proliferated less than T cells from controls. IBS patients had an increased polyclonally stimulated T-cell secretion of IL-1beta, which also weakly correlated with increased bowel habit dissatisfaction. Furthermore, despite normal frequencies of CD25high T cells in the blood of IBS patients, lower blood CD25high T-cell frequencies were modestly correlated with more bowel habit dissatisfaction and increased total IBS symptom severity., Conclusions: IBS patients have an increased frequency of activated T cells, demonstrated by the expression of activation markers and reduced proliferation in response to restimulation in vitro. The increased level of T-cell activation is consistent with the hypothesis of low-grade immune activation in IBS and may also be involved in symptom generation in IBS.

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

Objective: Altered small bowel motility and a high prevalence of small intestinal bacterial overgrowth (SIBO) has been observed in patients with liver cirrhosis. Our aim was to explore the relationship between motility abnormalities, portal hypertension, and SIBO., Methods: Twenty-four patients with liver cirrhosis were included. Twelve had portal hypertension (PH) and 12 had liver cirrhosis (LC) alone. Child-Pugh score was the same in the groups. Antroduodenojejunal pressure recordings were performed, and noninvasive variceal pressure measurements were undertaken. Thirty-two healthy volunteers served as a reference group. Bacterial cultures were obtained from jejunal aspirates., Results: The PH group had a higher proportion of individual pressure waves that were retrograde in the proximal duodenum during phase II (52% vs 13% vs 8% of propagated contractions; p < 0.001) as well as postprandially (49% vs 18% vs 13%; p < 0.01) compared with LC and controls, respectively. Long clusters were more common in PH than in controls (9.1 +/- 2.1 vs 4.9 +/- 0.8; p < 0.05), and a higher motility index in phase III in the proximal and distal duodenum was seen in the PH as compared with the other groups. The mean variceal pressure was 21 +/- 1 mm Hg. Motor abnormalities were not correlated to the level of variceal pressure. Thirty-three percent of the patients in the PH group but none in the LC group had SIBO., Conclusions: Abnormal small bowel motility and SIBO is common in patients with liver cirrhosis with concomitant portal hypertension. Portal hypertension per se might be significantly related to small bowel abnormalities observed in patients with liver cirrhosis.

Objectives: Quality of life is reduced in inflammatory bowel disease (IBD). Whether or not this is true in IBD patients in long-standing remission is unclear. Symptoms compatible with irritable bowel syndrome (IBS) are common in IBD patients in remission. The importance of psychological factors in this process is a matter of controversy., Methods: Forty-three patients with ulcerative colitis (UC) and 40 with Crohn's disease (CD), who had been in remission for at least 1 yr according to laboratory parameters and clinical and endoscopical appearance, were included. These patients completed four different self-administered questionnaires, evaluating GI symptoms, anxiety, depression, and psychological general well-being. The two patient groups were compared with the general population, and within-group comparisons in psychometric scores were made between patients with and without IBS-like symptoms., Results: The psychological well-being in IBD patients in long-standing remission was similar to that of the general population, despite the presence of more severe GI symptoms. CD patients reported more psychosocial dysfunction, reduced well-being, and GI symptoms than UC patients. Thirty-three percent of UC patients and 57% of CD patients had IBS-like symptoms. The group with IBS-like symptoms (both UC and CD) had higher levels of anxiety and depression and more reduced well-being than those without. Anxiety and reduced vitality were found to be independent predictors for IBS-like symptoms in these patients., Conclusion: The prevalence of IBS-like symptoms in IBD patients in long-standing remission is two to three times higher than that in the normal population. Psychological factors seem to be of importance in this process. However, as a group IBD patients in remission demonstrate psychological well-being comparable to that of the general population.