Mast cell activation and nutritional disorders in patients with hypermobility.

PURPOSE OF REVIEW: Individuals with joint hypermobility disorders are increasingly referred to gastroenterology services for support with the investigation and management of gastrointestinal complaints. Individuals can present with a myriad of complex coexisting diagnoses, the inter-relationship of which is unclear. This review discusses the proposed association between hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorder (HSD) with disorders of mast cell activation and provides an overview of gastrointestinal symptoms and nutritional outcomes in this patient cohort. RECENT FINDINGS: It is unclear whether a true association between hEDS/HSD and mast cell activation disorders exists. There is a high prevalence of nonspecific gastrointestinal symptoms in individuals with hEDS/HSD and patients may be at risk of macro-nutrient and micro-nutrient deficiencies, although the current evidence base is limited. SUMMARY: We advocate a pragmatic approach to the investigation and management of gastrointestinal symptoms in patients with hEDS/HSD. This centres on excluding organic pathology, discussing the overlap with disorders of gut-brain interactions, trialling evidence-based therapies targeting individual symptoms, and supporting nutritional deficiencies where present via the least invasive approach. Engagement with a broad multidisciplinary team is also important to support the holistic needs of this patient cohort.

Rejection of Fecal Immunochemical Tests Within the Lower Gastrointestinal Diagnostic Pathway: A Cohort Study.

INTRODUCTION/OBJECTIVES: The fecal immunochemical test (FIT) helps triage primary care patients at risk of colorectal cancer (CRC). Improving FIT returns has received recent attention, however uncertainty exists regarding the accurate completion of samples provided for laboratory analysis. This study aims to identify the rejection rate of returned FIT samples and determine rejection causes. METHODS: FIT samples from symptomatic patients within South Yorkshire, Bassetlaw, and North Derbyshire are processed at a central laboratory. Tests requests are made from 225 GP practices, which serve an estimated 2 million population. This study describes a retrospective review of FIT samples received in the central laboratory between 01/09/19 and 31/12/22. Locally held data was interrogated in March 2023 to determine the number of FIT samples received and rejected during the study period. Documented reasons for rejection were explored to identify common themes. RESULTS: Total FIT specimens received during the study period was 126 422. Of these, 5190 (4.1%) were rejected. Monthly rejection rates fell from 17.4% in September 2019 to 1.3% in December 2022 (P < .001). Sampling errors were the most frequent cause for FIT rejection (2151/5190), with other causes including: expired specimen; no sample collection date/ time, no request form, incomplete patient information and illegible handwriting. CONCLUSIONS: This is the first study exploring FIT rejection rates in symptomatic primary care patients, which shows improvements in rejection rates over time. Targeted interventions could improve rejection rates further, thereby reducing NHS resource use and costs and diagnostic delays.

Randomized trial in postprandial functional dyspepsia: Reassurance and diagnostic explanation with or without traditional dietary advice.

BACKGROUND: Almost 80% of individuals with functional dyspepsia experience meal-related symptoms and are diagnosed with postprandial distress syndrome (PDS). However, studies evaluating dietary modifications in PDS are sparse. We performed a single-center randomized trial comparing reassurance and diagnostic explanation (RADE) with or without traditional dietary advice (TDA) in PDS. METHODS: Following a normal upper gastrointestinal endoscopy, individuals with PDS were randomized to a leaflet providing RADE ± TDA; the latter recommending small, regular meals and reducing the intake of caffeine/alcohol/fizzy drinks and high-fat/processed/spicy foods. Questionnaires were completed over 4 weeks, including self-reported adequate relief of dyspeptic symptoms, and the validated Leuven Postprandial Distress Scale (LPDS), Gastrointestinal Symptom Rating Scale, and Nepean Dyspepsia Index for quality of life. The primary endpoint(s) to define clinical response were (i) ≥50% adequate relief of dyspeptic symptoms and (ii) >0.5-point reduction in the PDS subscale of the LPDS (calculated as the mean scores for early satiety, postprandial fullness, and upper abdominal bloating). KEY RESULTS: Of the 53 patients with PDS, 27 were assigned RADE-alone and 26 to additional TDA. Baseline characteristics were similar between groups, with a mean age of 39 years, 70% female, 83% white British, and coexistent irritable bowel syndrome in 66%. The primary endpoints of (i) adequate relief of dyspeptic symptoms were met by 33% (n = 9) assigned RADE-alone versus 39% (n = 10) with TDA; p-value = 0.70, while (ii) a reduction of >0.5 points in the PDS subscale was met by 37% (n = 10) assigned RADE-alone versus 27% (n = 7) with TDA; p-value = 0.43. Response rates did not differ according to irritable bowel syndrome status. There were no significant between-group changes in the gastrointestinal symptom rating scale and dyspepsia quality of life. CONCLUSIONS & INFERENCES: This study of predominantly white British patients with PDS found the addition of TDA did not lead to significantly greater symptom reduction compared with RADE alone. Alternate dietary strategies should be explored in this cohort.

Does a Gluten-Free Diet Improve Quality of Life and Sleep in Patients with Non-Coeliac Gluten/Wheat Sensitivity?

INTRODUCTION: The role of a gluten-free diet (GFD) in Non-Coeliac Gluten/Wheat Sensitivity (NCGWS) is unclear. We present the largest study comparing adherence to a GFD in patients with Coeliac Disease (CD) and NCGWS and assess its impact on quality of life (QoL) and sleep in patients with NCGWS. METHODS: Patients with NCGWS at a tertiary centre completed the Coeliac Disease Adherence Test (CDAT), Coeliac Symptom Index (CSI) and Sleep Condition Indicator (SCI). Higher CDAT scores indicate worse adherence, higher CSI scores indicate poorer QoL, and higher SCI scores indicate better sleep. CDAT scores were correlated with CSI and SCI scores. A second group of patients with CD completed the CDAT questionnaire only. Results were compared with the CDAT responses from the NCGWS group. RESULTS: For the NCGWS cohort (n = 125), the median CDAT score was 17/35, indicating poor adherence. The median CSI score was 44/80, with 40% of scores associated with a poor QoL. The median SCI score was 14/32, and DSM-V criteria for insomnia was met by 42% of patients. There was a positive correlation between CSI and CDAT scores (r = 0.59, p < 0.0001) and a negative correlation between SCI and CDAT scores (r = -0.37, p = 0.0002). In the CD cohort (n = 170), the median CDAT score was 13/35. Patients with NCGWS had poorer adherence compared to CD (CDAT: 17.0 vs. 13.0, respectively, p = 0.0001). CONCLUSION: Patients with NCGWS adhere to a GFD less than those with CD. Poorer adherence to a GFD in patients with NCGWS correlates with a worse QoL and sleep performance.

Diagnostic yield of upper gastrointestinal endoscopy in patients attending a UK centre with symptoms compatible with Rome IV functional dyspepsia.

Background: Dyspeptic symptoms are common and mainly due to functional dyspepsia (FD). The Rome IV criteria mandate a normal upper gastrointestinal (UGI) endoscopy before diagnosing FD. However, endoscopies are costly, resource-intensive procedures that generate substantial waste. Hence, simpler means of diagnosing FD are desirable. Objectives: To determine what proportion of UGI endoscopies are represented by patients with symptoms compatible with Rome IV FD, and the diagnostic yield in this cohort stratified according to alarm features. Methods: Adult patients attending a UK centre for outpatient UGI endoscopy completed a preprocedure questionnaire on demographics, medical history, alarm features, mood, somatisation and GI symptoms. Alarm features were defined as age ≥55 years, dysphagia, anaemia, unintentional weight loss, UGI bleed or a family history of UGI cancer. Clinically significant endoscopic findings were cancers, Barrett's oesophagus, erosive oesophagitis, peptic ulcers or strictures. Results: Of 387 patients attending for an outpatient non-surveillance diagnostic UGI endoscopy, 221 had symptoms compatible with FD whereas 166 did not. Approximately 80% in both groups had alarm features, with a similar prevalence of clinically significant endoscopic findings at ~10%. UGI endoscopy was normal in a cohort of 9% (n=35) with symptoms compatible with FD and no alarm features, while benign peptic ulcer was noted in two of 29 cases without FD symptoms and no alarm features. Conclusion: 1-in-10 UGI endoscopies are performed in patients with symptoms compatible with FD and no alarm features, in whom there is no diagnostic yield. We recommend such patients receive a positive diagnosis of FD without endoscopy.

Impact of Co-existing Paroxysmal Atrial Fibrillation on Different Outcomes of Hospitalized COVID-19 Patients: Nationwide Inpatient Sample Analysis (2020) With Propensity Score Matching.

Various studies in the medical literature reported significant cardiovascular involvement in patients with coronavirus disease 2019 (COVID-19) pneumonia. Atrial fibrillation (AF) was identified as the most commonly observed arrhythmia complicating COVID-19 infection with an increased risk of short-term mortality. We used the National Inpatient Sample Database (NIS) of 2020 to conduct this retrospective cohort study. Our study's population consisted of adult patients hospitalized for COVID-19 Pneumonia with or without the presence of paroxysmal atrial fibrillation (PAF). Encounters with COVID-19 and co-existing PAF had higher adjusted odds of inpatient mortality (Adjusted odds ratio [aOR]: 1.19, 95% CI: 1.11-1.28, P < 0.001), longer mean length of hospital stay (LOS) of 1.17 days (95% confidence interval [CI]: 1.03-1.38, P < 0.001), and higher odds of different in-hospital complications. Based on these results, conducting more prospective/retrospective cohort studies with an emphasis on long-term follow-up on patients who develop PAF following COVID-19 infection is warranted.

The national prevalence of disorders of gut brain interaction in the United Kingdom in comparison to their worldwide prevalence: Results from the Rome foundation global epidemiology study.

BACKGROUND: There are minimal epidemiological data comparing the burden of disorders of gut brain interaction (DGBI) in the UK with other countries. We compared the prevalence of DGBI in the UK with other countries that participated in the Rome Foundation Global Epidemiology Study (RFGES) online. METHODS: Participants from 26 countries completed the RFGES survey online including the Rome IV diagnostic questionnaire and an in-depth supplemental questionnaire with questions about dietary habits. UK sociodemographic and prevalence data were compared with the other 25 countries pooled together. KEY RESULTS: The proportion of participants with at least one DGBI was lower in UK participants compared with in the other 25 countries (37.6% 95% CI 35.5%-39.7% vs. 41.2%; 95% CI 40.8%-41.6%, p = 0.001). The UK prevalence of 14 of 22 Rome IV DGBI, including irritable bowel syndrome (4.3%) and functional dyspepsia (6.8%), was similar to the other countries. Fecal incontinence, opioid-induced constipation, chronic nausea and vomiting, and cannabinoid hyperemesis (p < 0.05) were more prevalent in the UK. Cyclic vomiting, functional constipation, unspecified functional bowel disorder, and proctalgia fugax (p < 0.05) were more prevalent in the other 25 countries. Diet in the UK population consisted of higher consumption of meat and milk (p < 0.001), and lower consumption of rice, fruit, eggs, tofu, pasta, vegetables/legumes, and fish (p < 0.001). CONCLUSIONS AND INFERENCES: The prevalence and burden of DGBI is consistently high in the UK and in the rest of the world. Opioid prescribing, cultural, dietary, and lifestyle factors may contribute to differences in the prevalence of some DGBI between the UK and other countries.

Fecal Immunochemical Testing in Patients With Low-Risk Symptoms of Colorectal Cancer: A Diagnostic Accuracy Study.

BACKGROUND: The fecal immunochemical test (FIT) is recommended for triaging primary care patients in England with low-risk symptoms of colorectal cancer (CRC). The evidence underpinning recommendations by the National Institute for Health and Care Excellence had limitations, with a paucity of primary care evidence. This study examines the diagnostic accuracy of FIT in a defined low-risk symptom primary care population. PATIENTS AND METHODS: Consecutive symptomatic adult patients referred for a FIT between October and December 2019 were included. Patients were derived from 225 primary care practices in England. Serious colorectal diseases (CRC, high-risk polyps, and inflammatory bowel disease [IBD]) were identified through patient follow-up over 18 months, using both primary and secondary healthcare records. Performance characteristics of FIT are reported according to differing thresholds, including the currently recommended threshold of ≥10 µg hemoglobin per gram of feces (µg/g). RESULTS: A total of 3,506 patients were included in the final analysis. Of these, 708 had a positive FIT result (≥10 µg/g). The prevalence of CRC was 1.3%. FIT positivity declined from 20.2% to 5.8% and 4.5% at cutoffs of 10, 80, and 120 µg/g, respectively. The sensitivity of FIT at ≥10 µg/g to detect CRC was 91.1% (95% CI, 77.9%-97.1%); its specificity was 80.7% (95% CI, 79.3%-82.0%); the positive predictive value (PPV) was 5.8% (95% CI, 4.2%-7.8%); and the negative predictive value (NPV) was 99.9% (95% CI, 99.6%-99.95%). The area under the receiver operating characteristic curve was 0.93 (0.91-0.96). PPV and specificity increased, whereas sensitivity and NPV decreased when serious colorectal diseases (CRC, high-risk polyps, and IBD) were combined. Age, sex, socioeconomic deprivation, and anemia did not significantly influence FIT sensitivity on subgroup analysis. CONCLUSIONS: Utilization of FIT at a threshold ≥10 µg/g can safely triage patients with low-risk symptoms in primary care, with negative results effectively ruling out CRC.

British Society of Gastroenterology guidelines on the management of functional dyspepsia

Functional dyspepsia (FD) is a common disorder of gut­brain interaction, affecting approximately 7% of individuals in the community, with most patients managed in primary care. The last British Society of Gastroenterology (BSG) guideline for the management of dyspepsia was published in 1996. In the interim, substantial advances have been made in understanding the complex pathophysiology of FD, and there has been a considerable amount of new evidence published concerning its diagnosis and classification, with the advent of the Rome IV criteria, and management. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based diagnosis and treatment of patients. The approach to investigating the patient presenting with dyspepsia is discussed, and efficacy of drugs in FD summarised based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of pairwise and network meta-analyses. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system. These provide both the strength of the recommendations and the overall quality of evidence. Finally, in this guideline, we consider novel treatments that are in development, as well as highlighting areas of unmet need and priorities for future research.

Disorders of gut-brain interaction: Highly prevalent and burdensome yet under-taught within medical education.

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

British Society of Gastroenterology guidelines on the management of functional dyspepsia.

Functional dyspepsia (FD) is a common disorder of gut-brain interaction, affecting approximately 7% of individuals in the community, with most patients managed in primary care. The last British Society of Gastroenterology (BSG) guideline for the management of dyspepsia was published in 1996. In the interim, substantial advances have been made in understanding the complex pathophysiology of FD, and there has been a considerable amount of new evidence published concerning its diagnosis and classification, with the advent of the Rome IV criteria, and management. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based diagnosis and treatment of patients. The approach to investigating the patient presenting with dyspepsia is discussed, and efficacy of drugs in FD summarised based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of pairwise and network meta-analyses. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system. These provide both the strength of the recommendations and the overall quality of evidence. Finally, in this guideline, we consider novel treatments that are in development, as well as highlighting areas of unmet need and priorities for future research.

Prioritisation of lower gastrointestinal endoscopy during the COVID-19 pandemic: outcomes of a novel triage pathway.

Objective: The 2-week-wait (2ww) referral pathway is used in England to fast-track patients with suspected colorectal cancer (CRC). A two-stage triage pathway was used to prioritise lower gastrointestinal (LGI) endoscopy for suspected CRC during the COVID-19 pandemic. Method: All patients referred for an LGI endoscopy via a 2ww referral pathway between March 2020 and July 2020 were assessed. The first stage triaged patients to high, standard or low risk of CRC based on symptoms and faecal immunochemical test (FIT), and offered CT scans to those at high risk. The second stage, endoscopy prioritisation (EP), incorporated the CT results, FIT and symptoms to triage into four groups, EP1-EP4; with EP1 being the most urgent and EP4 the least. The primary outcome measure was CRC detection. Results: 514 patients were included. The risk of CRC was triaged as high in 190/514 patients (37%), standard in 274/514 patients (53%) and low in 50/514 (10%) patients. 422/514 patients (82%) underwent endoscopy with triage to EP1 in 52/422 (12%), EP2 in 105/422 (25%), EP3 in 210/422 (50%) and EP4 in 55/422 (13%). CRC was detected in 23 patients (5.4%). CRC was significantly more frequent in the EP1 group (23.1%, relative risk (RR)=16.2) and EP2 group (6.7%, RR=4.7) compared with EP3 group (1.4%). All CRC lesions were identified by CT imaging when performed prior to LGI endoscopy. Conclusion: This triage pathway designated 83% of patients with CRC to either EP1 or EP2. During a period of limited endoscopy provision, this pathway effectively prioritises endoscopy for those at greatest risk of CRC.

Efficacy and Acceptability of Dietary Therapies in Non-Constipated Irritable Bowel Syndrome: A Randomized Trial of Traditional Dietary Advice, the Low FODMAP Diet, and the Gluten-Free Diet.

BACKGROUND & AIMS: Various diets are proposed as first-line therapies for non-constipated irritable bowel syndrome (IBS) despite insufficient or low-quality evidence. We performed a randomized trial comparing traditional dietary advice (TDA) against the low FODMAP diet (LFD) and gluten-free diet (GFD). METHODS: Patients with Rome IV-defined non-constipated IBS were randomized to TDA, LFD, or GFD (the latter allowing for minute gluten cross-contamination). The primary end point was clinical response after 4 weeks of dietary intervention, as defined by ≥50-point reduction in IBS symptom severity score (IBS-SSS). Secondary end points included (1) changes in individual IBS-SSS items within clinical responders, (2) acceptability and food-related quality of life with dietary therapy, (3) changes in nutritional intake, (4) alterations in stool dysbiosis index, and (5) baseline factors associated with clinical response. RESULTS: The primary end point of ≥50-point reduction in IBS-SSS was met by 42% (n = 14/33) undertaking TDA, 55% (n = 18/33) for LFD, and 58% (n = 19/33) for GFD (P = .43). Responders had similar improvements in IBS-SSS items regardless of their allocated diet. Individuals found TDA cheaper (P < .01), less time-consuming to shop (P < .01), and easier to follow when eating out (P = .03) than the GFD and LFD. TDA was also easier to incorporate into daily life than the LFD (P = .02). Overall reductions in micronutrient and macronutrient intake did not significantly differ across the diets. However, the LFD group had the greatest reduction in total FODMAP content (27.7 g/day before intervention to 7.6 g/day at week 4) compared with the GFD (27.4 g/day to 22.4 g/day) and TDA (24.9 g/day to 15.2 g/day) (P < .01). Alterations in stool dysbiosis index were similar across the diets, with 22%-29% showing reduced dysbiosis, 35%-39% no change, and 35%-40% increased dysbiosis (P = .99). Baseline clinical characteristics and stool dysbiosis index did not predict response to dietary therapy. CONCLUSIONS: TDA, LFD, and GFD are effective approaches in non-constipated IBS, but TDA is the most patient-friendly in terms of cost and convenience. We recommend TDA as the first-choice dietary therapy in non-constipated IBS, with LFD and GFD reserved according to specific patient preferences and specialist dietetic input. CLINICALTRIALS: gov: NCT04072991.

An approximation of one-dimensional nonlinear Kortweg de Vries equation of order nine.

This research presents the approximate solution of nonlinear Korteweg-de Vries equation of order nine by a hybrid staggered one-dimensional Haar wavelet collocation method. In literature, the underlying equation is derived by generalizing the bilinear form of the standard nonlinear KdV equation. The highest order derivative is approximated by Haar series, whereas the lower order derivatives are attained by integration formula introduced by Chen and Hsiao in 1997. The findings are shown in the form of tables and a figure, demonstrating the proposed technique's convergence, robustness, and ease of application in a small number of collocation points.

Diagnostic Yield of Colonoscopy in Patients With Symptoms Compatible With Rome IV Functional Bowel Disorders.

BACKGROUND & AIMS: There is little data on the diagnostic yield of colonoscopy in patients with symptoms compatible with functional bowel disorders (FBDs). Previous studies have only focused on diagnostic outcomes of colonoscopy in those with suspected irritable bowel syndrome using historic Rome I-III criteria, whilst having partially assessed for alarm features and shown markedly conflicting results. There is also no colonoscopy outcome data for other FBDs, such as functional constipation or functional diarrhea. Using the contemporaneous Rome IV criteria we determined the diagnostic yield of colonoscopy in patients with symptoms compatible with a FBD, stratified diligently according to the presence or absence of alarm features. METHODS: Basic demographics, alarm features, and bowel symptoms using the Rome IV diagnostic questionnaire were collected prospectively from adults attending out-patient colonoscopy in 2019. Endoscopists were blinded to the questionnaire data. Organic disease was defined as the presence of inflammatory bowel disease, colorectal cancer, or microscopic colitis. RESULTS: 646 patients fulfilled symptom-based criteria for the following Rome IV FBDs: IBS (56%), functional diarrhea (27%) and functional constipation (17%). Almost all had alarm features (98%). The combined prevalence of organic disease was 12%, being lowest for functional constipation and IBS-constipation (∼6% each), followed by IBS-mixed (∼9%), and highest amongst functional diarrhea and IBS-diarrhea (∼17% each); p = .005. The increased prevalence of organic disease in diarrheal versus constipation disorders was accounted for by microscopic colitis (5.7% vs. 0%, p < .001) but not inflammatory bowel disease (7.2% vs. 4.0%, p = .2) or colorectal cancer (4.2% vs. 2.3%, p = .2). However, 1-in-4 chronic diarrhea patients - conceivably at risk for microscopic colitis - did not have colonic biopsies taken. Finally, only 11 of 646 (2%) patients were without alarm features, in whom colonoscopy was normal. CONCLUSIONS: Most patients with symptoms of FBDs who are referred for colonoscopy have alarm features. The presence of organic disease is significantly higher in diarrheal versus constipation disorders, with microscopic colitis largely accounting for the difference whilst also being a missed diagnostic opportunity. In those patients without alarm features, the diagnostic yield of colonoscopy was nil.

Greater Overlap of Rome IV Disorders of Gut-Brain Interactions Leads to Increased Disease Severity and Poorer Quality of Life.

BACKGROUND AND AIMS: Conditions such as irritable bowel syndrome (IBS), functional dyspepsia, and functional constipation are among the prevalent gastrointestinal (GI) disorders classified as disorders of gut-brain interaction (DGBI), which can adversely affect the lives of sufferers. This study aimed to assess the degree and consequences of overlapping DGBI in a large population-based global scale. METHODS: Internet survey data from 54,127 adults (49.1% women) in 26 countries were analyzed by 4 GI anatomic regions (esophageal, gastroduodenal, bowel, and anorectal). The number of DGBI-affected GI regions was assessed, including associations with sex, age, disease severity, quality of life, psychosocial variables, and health care utilization. RESULTS: A total of 40.3% of surveyed individuals met Rome IV criteria for a DGBI. The percentages with 1-4 DGBI-affected GI regions were 68.3%, 22.3%, 7.1%, and 2.3%, respectively. The IBS symptom severity score increased significantly from 1 (207.6) to 4 (291.6) regions, as did non-GI symptom reporting (somatization), anxiety and depression, concerns and embarrassment about bowel function, doctor visits, medications, and abdominal surgeries (all P < .0001). Quality of life decreased with increasing number of DGBI regions (P < .0001). In a logistic mixed model, non-GI symptoms (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.08-1.10), being very vs not concerned (OR, 2.55; 95% CI, 2.27-2.90), being very vs not embarrassed about bowel function (OR, 1.20; 95% CI, 1.08-1.33), and mean number of doctor visits (OR, 1.23; 95% CI, 1.115-1.32) were most strongly associated with number of DGBI regions. CONCLUSIONS: DGBI in multiple anatomic GI regions is associated with increased psychological comorbidity, health care utilization, and IBS severity. Physician awareness of overlap could improve quality of care, prevent unnecessary interventions, and yield more positive health outcomes.