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.

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.

Worldwide prevalence and burden of gastroparesis-like symptoms as defined by the United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis.

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

Irritable bowel syndrome: Factors of importance for disease-specific quality of life.

BACKGROUND: Irritable bowel syndrome patients report reduced disease-specific quality of life (IBSQOL). Factors of potential relevance for QOL include gastrointestinal (GI), psychological, and somatic symptoms, demographics, and GI motor and sensory abnormalities. OBJECTIVE: The aim of our study was to evaluate the relative importance of these factors on the different IBSQOL dimensions. METHODS: We included irritable bowel syndrome (IBS) patients who completed validated questionnaires to assess QOL, stool form and frequency, GI symptom severity, psychological distress, GI-specific anxiety, sense of coherence, and overall somatic symptom severity. Patients also underwent tests for oroanal transit time and rectal sensitivity. The nine dimensions of IBSQOL and their average (overall IBSQOL) were used as outcome variables, and factors associated with these were assessed using general linear models. RESULTS: We included 314 IBS patients (74% female, mean age 36.3 ± 12.2 years). Higher stool frequency, GI and overall somatic symptom severity, psychological distress, and GI-specific anxiety were independently associated with reduced overall IBSQOL, with the model explaining 60% of the variance (p < 0.001). In models using each of the nine dimensions as outcomes, different association of demographic factors, GI symptoms, overall somatic symptom severity, psychological factors and sense of coherence were associated with reduced IBSQOL, explaining 20%-60% of the variance, with GI-specific anxiety being the factor that contributed most frequently. Rectal sensitivity or oroanal transit time were not independently associated with any of the dimensions. CONCLUSION: Different combinations of demographic factors, GI and somatic symptoms, and psychological factors are of importance for the nine IBSQOL dimensions. Gastrointestinal-specific anxiety was the most important factor contributing to the majority of those dimensions in patients with 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.

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.

Postinfectious onset in functional dyspepsia is a risk factor for weight loss.

BACKGROUND: Functional dyspepsia (FD) is differentiated into two subgroups: the postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Acute gastroenteritis and Helicobacter pylori (HP) infection have been identified as risk factors for FD. It is unclear how these risk factors relate to Rome IV subgroups and their clinical impact. We aimed to study the association of postinfectious FD (PI-FD) and HP status with clinical profiles and weight loss. METHODS: Consecutive FD patients were assessed for symptom frequency and severity. Patients were identified as PDS, EPS or the overlap group according to severity scores. Additionally, PI history and HP status were determined. RESULTS: In a cohort of 459 FD-patients, 36% were characterized as having PDS, 9% as having EPS and 55% showed overlap. PI onset and positive HP status were reported by, respectively, 20% and 14% of patients, not significantly differing between subgroups (respectively, p = 0.31 and p = 0.40). Weight loss was reported by 63% in PDS, 36% in EPS and 56% in overlap patients (p = 0.011). Only early satiety severity correlated with more severe weight loss in the PDS (r 0.31, p < 0.0001) and overlap group (r 0.38, p < 0.0001). PI-FD patients were more likely to experience weight loss (OR 2.27, p = 0.0013). HP status was not significantly associated with weight loss (p = 0.90). CONCLUSION: In this cohort, PI onset of FD symptoms emerged as a risk factor for weight loss, but was not associated with the symptom patterns of PDS, EPS or overlap subgroups. Patients with HP infection were not more likely to experience important weight loss.

Predictors of Symptom-Specific Treatment Response to Dietary Interventions in Irritable Bowel Syndrome.

(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.

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.

The gastrointestinal tract in hunger and satiety signalling.

BACKGROUND: Different peripheral pathways are implicated in the regulation of the food ingestion-digestion cycle. METHODS: Narrative review on gastrointestinal mechanisms involved in satiety and hunger signalling. RESULTS: Combined mechano- and chemoreceptors, peripherally released peptide hormones and neural pathways provide feedback to the brain to determine sensations of hunger (increase energy intake) or satiation (cessation of energy intake) and regulate the human metabolism. The gastric accommodation reflex, which consists of a transient relaxation of the proximal stomach during food intake, has been identified as a major determinant of meal volume, through activation of tension-sensitive gastric mechanoreceptors. Motilin, whose release is the trigger of gastric Phase 3, has been identified as the major determinant of return of hunger after a meal. In addition, the release of several peptide hormones such as glucagon-like peptide 1 (GLP-1), cholecystokinin as well as motilin and ghrelin contributes to gut-brain signalling with relevance to control of hunger and satiety. A number of nutrients, such as bitter tastants, as well as pharmacological agents, such as endocannabinoid receptor antagonists and GLP-1 analogues act on these pathways to influence hunger, satiation and food intake. CONCLUSION: Gastrointestinal mechanisms such as gastric accommodation and motilin release are key determinants of satiety and hunger.

From Pre- and Probiotics to Post-Biotics: A Narrative Review.

BACKGROUND AND AIMS: gut microbiota (GM) is a complex ecosystem containing bacteria, viruses, fungi, and yeasts. It has several functions in the human body ranging from immunomodulation to metabolic. GM derangement is called dysbiosis and is involved in several host diseases. Pre-, probiotics, and symbiotics (PRE-PRO-SYMB) have been extensively developed and studied for GM re-modulation. Herein, we review the literature data regarding the new concept of postbiotics, starting from PRE-PRO-SYMB. METHODS: we conducted a search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials, and case series using the following keywords and acronyms and their associations: gut microbiota, prebiotics, probiotics, symbiotic, and postbiotics. RESULTS: postbiotics account for PRO components and metabolic products able to beneficially affect host health and GM. The deeper the knowledge about them, the greater their possible uses: the prevention and treatment of atopic, respiratory tract, and inflammatory bowel diseases. CONCLUSIONS: better knowledge about postbiotics can be useful for the prevention and treatment of several human body diseases, alone or as an add-on to PRE-PRO-SYMB.

Recent advances in diagnosis and management of irritable bowel syndrome.

PURPOSE OF REVIEW: This review summarizes recent progress in the diagnosis and management of irritable bowel syndrome, with a focus on dietary and microbiota aspects. RECENT FINDINGS: From a pathophysiological point of view, IBS is a multifactorial condition with both peripheral (transit) as central (visceral hypersensitivity, anxiety, depression) contribution in a cumulative fashion to the symptom pattern and severity. More recently, the focus has shifted to diet and microbiota. The number of dietary options that can be used for IBS and the understanding of determinants of their efficacy is rapidly increasing. Several studies have confirmed the efficacy of the low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet. Sucrose-isomaltase deficiency has emerged as pathogenetic mechanisms in a subset of patients, who do not respond to low FODMAP diet but may respond to starch and sucrose elimination. Herbal remedies, probiotics and secretagogues have been the topic of additional treatment trials. The efficacy of fecal microbiota transplantation in IBS is variable across studies, but donor selection is emerging as a critical factor. SUMMARY: Irritable bowel syndrome has evolved into a disorder of interaction between dietary factors and gut microbiota, with impact on bowel symptoms as well as extra-intestinal, central, symptoms. Dietary adjustments and treatments targeting the gut microbiota are areas of active research and clinical progress.

A survey on the impact of the COVID-19 pandemic on motility and functional investigations in Europe and considerations for recommencing activities in the early recovery phase.

BACKGROUND: The COVID-19 pandemic, declared by WHO on March 13, 2020, had a major global impact on the healthcare system and services. In the acute phase, the presence of the SARS-CoV-2 virus in the aerodigestive tract limited activities in the gastroenterology clinic and procedures to emergencies only. Motility and function testing was interrupted and as we enter the recovery phase, restarting these procedures requires a safety-focused approach with adequate infection prevention for patients and healthcare professionals. METHODS: We summarized knowledge on the presence of the SARS-CoV-2 virus in the aerodigestive tract and the risk of spread with motility and functional testing. We surveyed 39 European centers documenting how the pandemic affected activities and which measures they are considering for restarting these measurements. We propose recommendations based on current knowledge as applied in our center. RESULTS: Positioning of catheters for gastrointestinal motility tests carries a concern for aerosol-borne infection of healthcare workers. The risk is low with breath tests. The surveyed centers stopped almost all motility and function tests from the second half of March. The speed of restarting and the safety measures taken varied highly. CONCLUSIONS AND INFERENCES: Based on these findings, we provided recommendations and practical relevant information for motility and function test procedures in the COVID-19 pandemic era, to guarantee a high-quality patient care with adequate infection prevention.

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.