Efficacy and safety of STW 5-II for functional dyspepsia treatment: a patient data-based meta-analysis.

BACKGROUND: Functional dyspepsia (FD) is a chronic relapsing gastroduodenal disorder with limited treatment options. Herbal products, like the six-herb combination STW5-II, can target multiple FD gastrointestinal symptoms. In this meta-analysis, we evaluated the efficacy and safety of STW 5-II for overall FD, and key symptoms, based on Rome IV criteria. SUMMARY: We systematically screened the literature for randomized controlled clinical studies testing STW 5-II in FD. Meta-analysis was performed using data from individual patients with at least one key FD symptom (fullness, early satiety, or epigastric pain) of at least moderate severity at baseline. ANCOVA-based meta-analyses were performed on improvements in the total symptom sum score, and single symptoms, after 4 and 8 weeks. Safety data were analyzed by calculating odds ratios (ORs) for all adverse events. Four randomized controlled trials, including 613 patients, were identified, and two were eligible for efficacy analysis. STW 5-II significantly improved the FD symptom sum score (mean difference of 1.74 after 4 weeks, and 2.07 after 8 weeks), and key FD symptoms of fullness (0.28 and 0.29), early satiety (0.25 and 0.26), and epigastric/upper abdominal pain (0.26 and 0.3). Treatment-related or severe adverse events did not differ between STW5-II and placebo. KEY MESSAGES: The available data support that in patients meeting Rome IV criteria for FD, STW 5-II significantly improves overall FD and key symptoms after 4 and 8 weeks of treatment, with no safety difference compared to placebo. Thus, STW 5-II can be considered an effective and safe treatment option for FD.

Work productivity and activity impairment in disorders of gut-brain interaction: Data from the Rome Foundation Global Epidemiology Study.

BACKGROUND: Disorders of Gut-Brain Interaction (DGBI) are highly prevalent worldwide, but their effect on work productivity has not gained much attention. AIMS AND METHODS: We aimed to compare work productivity and activity impairment (WPAI) in persons with and without DGBI in a large population-based cohort and identify factors independently associated with WPAI in subjects with DGBI. Data were collected from Germany, Israel, Italy, Japan, the Netherlands, Poland, Spain and Sweden via Internet surveys as part of the Rome Foundation Global Epidemiology Study. Apart from the Rome IV diagnostic questionnaire, questionnaires evaluating WPAI related to general health (WPAI:GH), psychological distress (PHQ-4), somatic symptom severity (PHQ-15) and other factors were assessed. RESULTS: Of the 16,820 subjects, 7111 met the criteria for DGBI according to the Rome IV diagnostic questionnaire. Subjects with DGBI were younger (median (interquartile range) age 43 (31-58) vs. 47 (33-62)) and more often female (59.0% vs. 43.7%) compared to subjects without DGBI. Subjects with DGBI had higher absenteeism, presenteeism (poor work productivity due to illness), overall work impairment and activity impairment (p < 0.001) compared with subjects without. For subjects with DGBI affecting more than one anatomical region, WPAI was incrementally higher for each additional region. There were significant differences in WPAI for subjects with DGBI in different countries. Subjects from Sweden had the highest overall work impairment and from Poland the lowest. Using multiple linear regression, male sex, fatigue, psychological distress, somatic symptom severity and number of anatomical regions were independently associated with overall work impairment (p < 0.05 for all). CONCLUSION: In the general population, people with DGBI have substantial WPAI compared with those without DGBI. The reasons for these findings should be explored further, but having multiple DGBI, psychological distress, fatigue and somatic symptom severity seem to contribute to this impairment associated with DGBI.

Face-to-face interviews versus Internet surveys: Comparison of two data collection methods in the Rome foundation global epidemiology study: Implications for population-based research.

BACKGROUND AND AIMS: The Rome Foundation Global Epidemiology Study (RFGES) assessed the prevalence, burden, and associated factors of Disorders of Gut-Brain Interaction (DGBI) in 33 countries around the world. Achieving worldwide sampling necessitated use of two different surveying methods: In-person household interviews (9 countries) and Internet surveys (26 countries). Two countries, China and Turkey, were surveyed with both methods. This paper examines the differences in the survey results with the two methods, as well as likely reasons for those differences. METHODS: The two RFGES survey methods are described in detail, and differences in DGBI findings summarized for household versus Internet surveys globally, and in more detail for China and Turkey. Logistic regression analysis was used to elucidate factors contributing to these differences. RESULTS: Overall, DGBI were only half as prevalent when assessed with household vs Internet surveys. Similar patterns of methodology-related DGBI differences were seen within both China and Turkey, but prevalence differences between the survey methods were dramatically larger in Turkey. No clear reasons for outcome differences by survey method were identified, although greater relative reduction in bowel and anorectal versus upper gastrointestinal disorders when household versus Internet surveying was used suggests an inhibiting influence of social sensitivity. CONCLUSIONS: The findings strongly indicate that besides affecting data quality, manpower needs and data collection time and costs, the choice of survey method is a substantial determinant of symptom reporting and DGBI prevalence outcomes. This has important implications for future DGBI research and epidemiological research more broadly.

A comparative study of disorders of gut-brain interaction in Western Europe and Asia based on the Rome foundation global epidemiology study.

OBJECTIVE: Many studies have been published on disorders of the gut-brain interaction (DGBI) in Asia and Western Europe, but no previous study has directly assessed the difference between the two regions. The aim was to compare the prevalence of DGBI in Asia and Western Europe. METHODS: We used data collected in a population-based Internet survey, the Rome Foundation Global Epidemiology Study, from countries in Western Europe (Belgium, France, Germany, Netherlands, Italy, Spain, Sweden, and the United Kingdom) and Asia (China, Japan, South Korea, and Singapore). We assessed DGBI diagnoses (Rome IV Adult Diagnostic Questionnaire), anxiety/depression (Patient Health Questionnaire-4, PHQ-4), non-GI somatic symptoms (PHQ-12), and access to and personal costs of doctor visits. RESULTS: The study included 9487 subjects in Asia and 16,314 in Western Europe. Overall, 38.0% had at least one DGBI; younger age, female sex, and higher scores on PHQ4 and PHQ12 were all associated with DGBI. The prevalence of having at least one DGBI was higher in Western Europe than in Asia (39.1% vs 36.1%, OR 1.14 [95% CI 1.08-1.20]). This difference was also observed for DGBI by anatomical regions, most prominently esophageal DGBI (OR 1.67 [1.48-1.88]). After adjustment, the difference in DGBI prevalence diminished and psychological (PHQ-4) and non-GI somatic symptoms (PHQ-12) had the greatest effect on the odds ratio estimates. CONCLUSION: The prevalence of DGBI is generally higher in Western Europe compared to Asia. A considerable portion of the observed difference in prevalence rates seems to be explained by more severe psychological and non-GI somatic symptoms in Western Europe.

Functional Abdominal Cramping Pain: Expert Practical Guidance.

Functional abdominal cramping pain (FACP) is a common complaint, which may present either on its own or in association with a functional gastrointestinal disorder. It is likely caused by a variety of, probably partly unknown, etiologies. Effective management of FACP can be challenging owing to the lack of usable diagnostic tools and the availability of a diverse range of treatment approaches. Practical guidance for their selection and use is limited. The objective of this article is to present a working definition of FACP based on expert consensus, and to propose practical strategies for the diagnosis and management of this condition for physicians, pharmacists, and patients. A panel of experts on functional gastrointestinal disorders was convened to participate in workshop activities aimed at defining FACP and agreeing upon a recommended sequence of diagnostic criteria and management recommendations. The key principles forming the foundation of the definition of FACP and suggested management algorithms include the primacy of cramping pain as the distinguishing symptom; the importance of recognizing and acting upon alarm signals of potential structural disease; the recognition of known causes that might be addressed through lifestyle adjustment; and the central role of antispasmodics in the treatment of FACP. The proposed algorithm is intended to assist physicians in reaching a meaningful diagnostic endpoint based on patient-reported symptoms of FACP. We also discuss how this algorithm may be adapted for use by pharmacists and patients.

The serotonin receptor 3E variant is a risk factor for female IBS-D.

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT3Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D.

Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome: A multicenter retrospective study.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) of the serotonin type 3 receptor subunit (HTR3) genes have been associated with psychosomatic symptoms, but it is not clear whether these associations exist in irritable bowel syndrome (IBS). AIM: To assess the association of HTR3 polymorphisms with depressive, anxiety, and somatization symptoms in individuals with IBS. METHODS: In this retrospective study, 623 participants with IBS were recruited from five specialty centers in Germany, Sweden, the United States, the United Kingdom, and Ireland. Depressive, anxiety, and somatization symptoms and sociodemographic characteristics were collected. Four functional SNPs - HTR3A c.-42C>T, HTR3B c.386A>C, HTR3C c.489C>A, and HTR3E c.*76G>A - were genotyped and analyzed using the dominant and recessive models. We also performed separate analyses for sex and IBS subtypes. SNP scores were calculated as the number of minor alleles of the SNPs above. The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays. RESULTS: Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model (F depressive = 7.475, P depressive = 0.006; F anxiety = 6.535, P anxiety = 0.011). A higher SNP score (range 0-6) was linked to a worsened depressive symptoms score (F = 7.710, P-linear trend = 0.006) in IBS. The potential relevance of the HTR3C SNP was corroborated, showing changes in the expression level of 5-HT3AC variant receptors. CONCLUSION: We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS. The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.

Persistence of gastrointestinal symptoms in irritable bowel syndrome and ulcerative colitis: study protocol for a three-arm randomised controlled trial (SOMA.GUT-RCT).

INTRODUCTION: Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are distressing chronic diseases associated with abdominal pain and altered bowel habits of unknown aetiology. Results from previous studies indicate that, across both diseases, increased levels of illness-related anxiety and dysfunctional symptom expectations contribute to symptom persistence. Thus, comparing both disorders with regard to common and disease-specific factors in the persistence and modification of gastrointestinal symptoms seems justified. Our primary hypothesis is that persistent gastrointestinal symptoms in UC and IBS can be improved by modifying dysfunctional symptom expectations and illness-related anxiety using expectation management strategies. METHODS AND ANALYSIS: To assess the extent to which persistent somatic symptoms are modifiable in adult patients with UC and IBS, we will conduct an observer-blinded, three-arm randomised controlled trial. A total of 117 patients with UC and 117 patients with IBS will be randomised into three groups of equal size: targeted expectation management aiming to reduce illness-related anxiety and dysfunctional symptom expectations in addition to standard care (SC, intervention 1), non-specific supportive treatment in addition to SC (intervention 2) or SC only (control). Both active intervention groups will comprise three individual online consultation sessions and a booster session after 3 months. The primary outcome is baseline to postinterventional change in gastrointestinal symptom severity. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of the Hamburg Medical Association (2020-10198-BO-ff). The study will shed light onto the efficacy and mechanisms of action of a targeted expectation management intervention for persistent gastrointestinal symptoms in patients with UC and IBS. Furthermore, the detailed analysis of the complex biopsychosocial mechanisms will allow the further advancement of aetiological models and according evidence-based intervention strategies. TRIAL REGISTRATION NUMBER: ISRCTN30800023.

[Functional gastrointestinal disorders]. / Funktionelle gastrointestinale Störungen.

Approximately 50 % of chronic gastrointestinal symptoms in primary care can be attributed to functional gastrointestinal disorders (FGID). The most frequent gastrointestinal disorders are functional dyspepsia and irritable bowel syndrome. FGID are heterogenous with regards to the amount of symptoms and associated patient's impairment as well as to the underlying pathophysiological mechanisms. The biopsychosocial model of FGID assumes that biological, psychological and social factors interact in the predisposition to and in the initiation and course of FGID. The Rome Foundation defines FGID as disorders of the brain-gut interaction.Some physicians are hesitant to diagnose FGID due to the lack of specific biomarkers and/or structural changes in the gastrointestinal tract. In addition, some FGID to not respond well to conventional medications. Some patients are reluctant to accept the diagnosis of a FGID because they are afraid that a serious somatic disease has been missed and/or to be diagnosed as mentally ill.The use of interdisciplinary evidence-based guidelines for diagnosis and management of FGID can increase the certainty of diagnosis and the therapeutic options for physicians. In addition, these guidelines include recommendations how to explain the disorder and the management to the patient to establish a trustful doctor-patient relationship.FGID are diagnosed by the history of a typical cluster of symptoms and by guideline - recommended exclusion of somatic gastrointestinal disorders. FGID should be managed according to the main symptoms, the associated impairment and patients' preferences in a graduated approach by education and by dietary, pharmacological and psychological treatments.

[Psychosocial Support for People with Ulcerative Colitis and Irritable Bowel Syndrome: A Feasibility Study on Need, Focus and Viability]. / Psychosoziale Unterstützung von Menschen mit Colitis ulcerosa und Reizdarmsyndrom: eine Machbarkeitsstudie zu Bedarf, Fokus und Durchführbarkeit.

OBJECTIVES: Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are associated with high somatic symptom burden, reduced quality of life, and increased psychological distress. The subjective burden, the wish of many patients, and the involvement of psychological processes in symptom perception justify the development of psychosocial support services. We aimed to evaluate need, content and feasibility of such an offer. We included patients with both UC and RDS in order to identify disease-specific and trans-diagnostic aspects for psychosocial interventions. METHODS: We conducted telephone interviews with adult patients with UC or IBS using a standardized interview guide. We used numerical rating scales and open-ended questions to assess burden of and coping with the disease, disease-related expectations and anxiety, satisfaction with care, support and information needs, and preferences regarding support programs. We calculated descriptive metrics for quantitative variables as well as diagnosis-specific group comparisons. The answers to the open questions were summarised and counted in close accordance with the participants' statements. RESULTS: N=35 patients (UC: n = 15; IBS: n=20) participated (age: M=40.80, SD=14.56; 71% female). In both groups, patients showed a medium level of disease burden, with higher rates for IBS. Both groups reported disease-related anxiety, with higher levels in patients with IBS. Disease-related expectations did not differ between groups. Patients with IBS showed low satisfaction with care and felt less informed about their disease than patients with UC. Both groups indicated a high motivation of participating in a psychological support program and named illness-related expectations and illness anxiety as important components of such. DISCUSSION: The results confirm an increased need for psychosocial support and the relevance of disease-related expectations and anxiety for both diseases. Differences in symptom perception and care satisfaction indicate the importance of disease-specific elements in psychosocial therapy programs. CONCLUSION: The results demonstrate the high need for psychosocial support of patients with UC and IBS and indicate the feasibility of a psychosocial therapy program.

Persistent SOMAtic symptoms ACROSS diseases - from risk factors to modification: scientific framework and overarching protocol of the interdisciplinary SOMACROSS research unit (RU 5211).

INTRODUCTION: Persistent somatic symptoms (PSS) are highly prevalent in all areas of medicine; they are disabling for patients and costly for society. The subjective symptom burden often correlates poorly with the underlying disease severity, and patients' needs for effective treatment are far from being met. Initial evidence indicates that, in addition to disease-specific pathophysiological processes, psychological factors such as expectations, somatosensory amplification and prior illness experiences contribute to symptom persistence in functional as well as in somatic diseases. However, prospective studies investigating the transition from acute to chronic somatic symptoms, integrating pathophysiological, psychological and social factors, are scarce. A better understanding of the multifactorial mechanisms of symptom persistence is crucial for developing targeted mechanism-based interventions for effective prevention and treatment of PSS. Thus, the overall aim of the interdisciplinary SOMACROSS research unit is to identify generic and disease-specific risk factors and aetiological mechanisms of symptom persistence across a range of diseases. METHODS AND ANALYSIS: Seven projects will investigate risk factors and mechanisms of symptom persistence in a total of 3916 patients across 10 medical conditions. All study designs are prospective and share common assessment points, core instruments and outcome variables to allow comparison and validation of results across projects and conditions. Research will focus on the identification of generic and disease-specific mechanisms associated with unfavourable symptom course. The development of a multivariate prediction model will facilitate the understanding of the course of PSS across diseases. ETHICS AND DISSEMINATION: All individual SOMACROSS studies were approved by the ethics committees of the Medical Chambers Hamburg and Münster, Germany. Findings will be disseminated through peer-reviewed publications, scientific conferences and the involvement of relevant stakeholders, patients and the lay public. This interdisciplinary research unit will fundamentally contribute to earlier recognition of patients at risk, and to the development of prevention and tailored treatment concepts for PSS.

[The new guideline on irritable bowel syndrome: what is new?] / Die neue Leitlinie zum Reizdarmsyndrom: Was ändert sich?

IRRITABLE BOWEL SYNDROME: WHAT IS NEW?: The following refers only to irritable bowel syndrome (IBS) in adults. The new guideline includes a separate section on IBS for paediatric patients. Irritable bowel syndrome (IBS) presents as a heterogeneous picture with chronic abdominal complaints related to the bowel. These are usually accompanied by changes in bowel movements and lead to impaired quality of life. The genesis is multifactorial and there are complex underlying pathophysiological mechanisms associated with IBS. Thus, disturbances in various components of the gut-brain axis and the increasing importance of the microbiome can be identified. Various psychological comorbidities also play a role. DIAGNOSTICS: The diagnosis is made by a thorough anamnesis and symptom-oriented exclusion of important differential diagnoses. A subdivision into different subtypes depending on the main symptoms is beneficial for the further management of IBS patients. The diagnosis of IBS should be made as early as possible after reliable exclusion of the important differential diagnoses. If diarrhoea dominates as a symptom, a detailed differential diagnosis and functional diagnosis should be carried out. THERAPY: There is no proven causal and no established standard therapy. Due to the variable genesis and symptom manifestation of IBS, a broad spectrum of therapy options results, whereby there is no individual prediction regarding effectiveness and therefore every therapy is initially probationary. Symptom-independent general therapies that can be used for all subtypes include dietary methods (e. g. the low-FODMAP diet), probiotics, psychotherapy methods and complementary medicine. The choice of symptom-dependent drug treatments is made according to the subtype/main symptom. In the case of diarrhoea, bile acid binders, the non-absorbable antibiotic rifaximin or, in individual cases, 5-HT3-antagonists can be used in addition to loperamide. In constipation, prucalopride and linaclotide have value in addition to the use of soluble fibre and macrogol/other laxatives. For abdominal pain/cramps, studies show good results for spasmolytics, especially peppermint oil, and for tricyclic-type antidepressants. For the main symptom of flatulence, probiotics, rifaximin and especially the low-FODMAP diet can show positive results in studies.

Naldemedine is effective in the treatment of opioid-induced constipation in patients with chronic non-cancer pain who had a poor response to laxatives.

BACKGROUND: Two studies demonstrated the efficacy and safety of naldemedine in adult patients with chronic non-cancer pain and opioid-induced constipation (OIC). However, no studies have compared the efficacy of peripherally acting µ-opioid receptor antagonists in patients with adequate and inadequate responses to prior OIC therapy with laxatives. This post hoc analysis of integrated data from the two previous studies compared the efficacy of naldemedine in patients who were unsuccessfully treated with laxatives [poor laxative responders (PLRs)] with those who either did not receive laxatives >30 days prior to screening or those who only received rescue laxative at or after screening (non-PLRs). METHODS: Patients with OIC were randomized to once-daily treatment with naldemedine 0.2 mg or placebo. The primary efficacy endpoint was the proportion of responders [⩾3 spontaneous bowel movements (SBMs)/week and an increase from baseline of ⩾1 SBM/week for ⩾9 weeks of the 12-week treatment period and ⩾3 weeks of the final 4 weeks of the 12-week treatment period]. Additional endpoints included change in SBM frequency, change in frequency of SBMs without straining, proportion of complete SBM (CSBM) responders, change in CSBM frequency, and time to first SBM. Treatment-emergent adverse events (TEAEs) were assessed. RESULTS: The analysis included 538 (317 PLRs, 221 non-PLRs) and 537 (311 PLRs, 226 non-PLRs) patients in the naldemedine and placebo arms, respectively. There were significantly more responders in the naldemedine PLR (46.4%; p < 0.0001) and non-PLR (54.3%; p = 0.0009) subgroups versus the placebo groups (30.2% and 38.9%, respectively). In both the PLR and non-PLR subgroups, naldemedine treatment was superior to placebo on all additional endpoints. Overall incidence of TEAEs in the PLR subgroups treated with naldemedine or placebo was similar. CONCLUSION: This integrated analysis further supports the efficacy and tolerability of naldemedine in the treatment of OIC and demonstrates a consistent effect in both PLR and non-PLR subgroups.[ClinicalTrials.gov identifier: NCT01965158 and NCT01993940].

The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS-C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow-up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS-C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.

Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study.

BACKGROUND & AIMS: Although functional gastrointestinal disorders (FGIDs), now called disorders of gut-brain interaction, have major economic effects on health care systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents. METHODS: Data were collected via the Internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for Internet and household groups, so data analyses were conducted and reported separately. RESULTS: Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.3% persons who completed the Internet surveys (95% confidence interval [CI], 39.9-40.7) and 20.7% of persons who completed the household surveys (95% CI, 20.2-21.3). FGIDs were more prevalent among women than men, based on responses to the Internet survey (odds ratio, 1.7; 95% CI, 1.6-1.7) and household survey (odds ratio, 1.3; 95% CI, 1.3-1.4). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the Internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%). CONCLUSIONS: In a large-scale multinational study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and health care use. Although the absolute prevalence was higher among Internet respondents, similar trends and relative distributions were found in people who completed Internet vs personal interviews.