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

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

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

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

Global prevalence and burden of meal-related abdominal pain.

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

Managing pain in irritable bowel syndrome: current perspectives and best practice.

INTRODUCTION: Irritable bowel syndrome (IBS) is characterized by chronic symptoms (>6 months) of abdominal pain in combination with a disturbed bowel habit. There is an association between the intensity of abdominal pain and the need for health care utilization. A bidirectionally disordered gut-brain interaction is central in the pathophysiology of IBS where a number of factors, gastrointestinal and non-gastrointestinal, can contribute to the illness experience. In order to treat abdominal pain in IBS, mapping these factors in a multidimensional clinical profile is helpful. AREAS COVERED: This review covers basic epidemiology and pathophysiology of abdominal pain in IBS, the diagnostic approach, and a multidimensional treatment model where the management of abdominal pain is in focus. EXPERT OPINION: A personalized treatment of abdominal pain in IBS is possible in patients who understand the diagnosis, the potential of therapies used, and where a good continuity in the patient-doctor relationship is established.

Mechanisms underlying food-related symptoms in disorders of gut-brain interaction: Course ahead in research and clinical practice.

A subgroup of patients with a disorder of gut-brain interaction (DGBI) report symptoms such as abdominal pain, gas-related symptoms, dyspeptic symptoms and loose stool or urgency after meal intake. Therefore, the effect of several dietary therapies including fibre-rich or restrictive diets have already been studied in patients with irritable bowel syndrome, functional abdominal bloating or distention, and functional dyspepsia. However, there is a paucity of studies in the literature on the mechanisms underlying food-related symptoms. Therefore, this review focuses on these potential mechanisms and explains the role of nutrient sensing and tasting, physical considerations, malabsorption or allergy-like reaction to food and its interaction with microbiota. In addition, it emphasizes the importance of future research and clinical practice regarding food-related symptoms in patients with a DGBI.

Associations between postprandial symptoms, hydrogen and methane production, and transit time in irritable bowel syndrome.

BACKGROUND: Abnormal oroanal transit time (OATT) and visceral hypersensitivity are key pathophysiological factors in irritable bowel syndrome (IBS). The lactulose nutrient challenge test (LNCT) has been developed to assess the postprandial symptoms and gut microbial fermentation. We aimed to investigate associations between OATT, rectal sensitivity, and LNCT in IBS patients. METHODS: We included 263 IBS patients from two study cohorts, where the link between pathophysiology and symptoms was investigated. During the LNCT, severity of postprandial symptoms was graded, and breath hydrogen/methane concentrations were measured after ingestion of a combined lactulose nutrient drink every 15 min for 4 h. The patients underwent rectal sensitivity (rectal barostat) and OATT (radiopaque markers) investigations. Comorbid conditions (functional dyspepsia, anxiety, depression, and somatization) were assessed with questionnaires. KEY RESULTS: After controlling for comorbid conditions, rectal sensitivity was associated with abdominal pain (p < 0.05), and more rapid OATT was associated with higher severity of abdominal discomfort, rumbling, nausea, and urgency (p < 0.05 for all) both pre- and post-prandially. Postprandial nausea, urgency, and abdominal pain changed differently over time depending on OATT (p < 0.05 for all). OATT, but not rectal sensitivity, was associated with hydrogen and methane concentrations (p = 0.002 for both). Trajectories over time of postprandial symptoms and exhaled hydrogen/methane concentrations were correlated with different correlations depending on OATT. CONCLUSION AND INFERENCES: This study highlights the importance of oroanal transit and hydrogen and methane production in the pathophysiology of IBS and increases our understanding of pathophysiological factors involved in postprandial symptom generation. Treatments targeting oroanal transit and hydrogen and methane production may improve specific postprandial symptoms.

Treatments targeting the luminal gut microbiota in patients with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction affecting 4% of the world's population. Patients with IBS experience chronic or recurrent abdominal pain in combination with altered bowel habits (diarrhea and/or constipation), and have reduced quality of life. Despite the high prevalence and substantial burden of IBS, its pathophysiology is incompletely understood and remains to be elucidated. The importance of the gut microenvironment has been highlighted in IBS, as there are signs that the gut microbiota of patients differs from healthy controls. Recent studies have aimed to alter the gut microbiota and thereby, attempted to alleviate gastrointestinal symptoms in IBS patients. We highlighted recent advances in common treatments that are targeting the luminal gut microbiota in IBS.

Irritable bowel syndrome with food-related symptoms: Future directions in the clinical management.

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

Low FODMAP diet reduces gastrointestinal symptoms in irritable bowel syndrome and clinical response could be predicted by symptom severity: A randomized crossover trial.

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

Randomised controlled trial: effects of gluten-free diet on symptoms and the gut microenvironment in irritable bowel syndrome.

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

Gluten and fructan intake and their associations with gastrointestinal symptoms in irritable bowel syndrome: A food diary study.

BACKGROUND & AIMS: Wheat contains several components, including gluten and fructan, that may be associated with gastrointestinal symptoms (GI) in irritable bowel syndrome (IBS). The aims of the study were to determine the average daily intake of gluten, investigate the association of gluten and GI symptoms, as well as the association between fructan and GI symptoms in IBS subjects. METHODS: We assessed dietary intake, including total energy, and calculated average gluten and fructan intake in this 4-day food diary study. The subjects reported GI symptoms using the validated Gastrointestinal Symptom Rating Scale-IBS (GSRS-IBS). RESULTS: In total, 147 IBS subjects (116 females) were included in this study. The median (IQR) intake of gluten was 11.0 (7.5-15.4) (range: 0.6-52.1) g/day, and this intake was significantly higher for males (16.2 (11.5-18.8), g/day) compared with females (10.3 (7.3-13.2), g/day) (P ≤ 0.001). For analyses purposes, the subjects were stratified in tertiles of gluten intake. Median (IQR) overall GI symptom severity (GSRS-IBS) was significantly worse for the subjects with the lowest (52 (45-57)) and intermediate gluten intake (51 (43-58)), compared with the highest gluten intake (45 (37-50), P ≤ 0.05, and P ≤ 0.01 respectively). In addition, caloric intake was significantly lower in subjects with the lowest (1905 ± 446, kcal/day) and intermediate gluten intake (1854 ± 432, kcal/day), compared with subjects with the highest gluten intake (2305 ± 411, kcal/day), P < 0.001 for both. Analyses of the stratified fructan tertiles resulted in no significant differences in GSRS-IBS. CONCLUSIONS: The mean intake of gluten varies substantially among subjects with IBS, and IBS subjects with more severe GI symptoms have lower intake of gluten and calories. TRIAL REGISTRY: (http://www.clinicaltrials.gov): Registered under Clinical Trial number NCT02970591.

Pharmacological Therapies and Their Clinical Targets in Irritable Bowel Syndrome With Diarrhea.

Irritable bowel syndrome (IBS) is one of the most common disorders of the gut-brain axis, which affects approximately 4% of the global population. The Rome IV criteria define IBS as chronic or recurrent abdominal pain associated with altered bowel habits. Patients can be categorized in four subtypes: IBS with predominant constipation (IBS-C), predominant diarrhea (IBS-D), mixed bowel habits (IBS-M), and unclassified (IBS-U). IBS is associated with a lower quality of life, reduced work productivity, and high healthcare costs. When comparing subtypes, patients with IBS-D report lower disease related quality of life. Due to the scope of this review, we have solely focused on patients with IBS-D. Choosing the right pharmacological treatment in these patients remains challenging due to the heterogeneous patient population, patients' expectation of the treatment outcome, unavailability of efficacious drugs, and the multifactorial and incompletely understood underlying pathophysiology. Currently, pharmacological treatment options target individual symptoms, such as abdominal pain, altered bowel habits, and bloating. In this review, we aimed to summarize the current and recent pharmacological treatment options in IBS-D, targeting the predominant gastrointestinal symptoms. Additionally, we proposed a pharmacological treatment algorithm which healthcare professionals could use when treating individual patients with IBS-D.

The Dietary Management of Patients with Irritable Bowel Syndrome: A Narrative Review of the Existing and Emerging Evidence.

Even though irritable bowel syndrome (IBS) has been known for more than 150 years, it still remains one of the research challenges of the 21st century. According to the current diagnostic Rome IV criteria, IBS is characterized by abdominal pain associated with defecation and/or a change in bowel habit, in the absence of detectable organic causes. Symptoms interfere with the daily life of patients, reduce health-related quality of life and lower the work productivity. Despite the high prevalence of approximately 10%, its pathophysiology is only partly understood and seems multifactorial. However, many patients report symptoms to be meal-related and certain ingested foods may generate an exaggerated gastrointestinal response. Patients tend to avoid and even exclude certain food products to relieve their symptoms, which could affect nutritional quality. We performed a narrative paper review of the existing and emerging evidence regarding dietary management of IBS patients, with the aim to enhance our understanding of how to move towards an individualized dietary approach for IBS patients in the near future.