Törnblom, Hans

ABSTRACT Background Data on the global prevalence of alarm features in the general population and among individuals with disorders of gut–brain interaction (DGBI) are limited. Methods We analysed data from the Rome Foundation Global Epidemiology Study to estimate the prevalence of fourteen self‐reported alarm features in the global population and among individuals with Rome IV defined DGBI, including 54,127 participants from 26 countries. Differences between participants with and without DGBI were evaluated in a sample excluding those with self‐reported organic gastrointestinal disease, using univariable logistic regression. Analyses were stratified by age (< 50 vs. ≥ 50 years). Results Alarm features were reported by 63.1% of participants aged < 50 years and 51.8% of those aged ≥ 50 years. Individual self‐reported alarm features ranged from 0.9% to 18.3% in younger participants to 0.3%–13.3% in older participants. Haematemesis was the least frequently reported feature, while a major change in bowel movements was the most frequent in both age groups. Self‐reported alarm features were more frequent among participants with than without DGBI (< 50 years: 75.3% vs. 50.7%; OR 3.0 [2.8–3.1]; ≥ 50 years: 67.5% vs. 38.8%; OR 3.3 [3.1–3.5]). Participants with DGBI were also more likely to report multiple alarm features. Discussion Self‐reported alarm features are common in the general population and more prevalent among individuals with DGBI. These findings underscore the importance of interpreting alarm features within a broader clinical context rather than in isolation. Further studies are needed to clarify the diagnostic utility of alarm features in unselected populations, particularly among individuals with DGBI.

The accurate diagnosis of disorders of gut-brain interaction (DGBI), such as functional dyspepsia and irritable bowel syndrome, is crucial for improving patient symptoms, outcomes and ultimately, quality of life. However, busy clinicians often face challenges in diagnosing and managing these conditions, particularly when patients present with non-specific gastrointestinal symptoms together with psychosocial distress and/or social issues. DGBI are among the most common reasons for gastroenterology referral, with a global prevalence of approximately 40% in adults based on large-scale epidemiologic studies. While diagnostic algorithms aid in positively identifying DGBI, they often overlook key factors influencing treatment decisions. The Rome V Multidimensional Clinical Profile (MDCP) offers a comprehensive, patient-centered framework that extends beyond diagnosis alone. It integrates five core domains: (1) the primary diagnosis, (2) clinical modifiers, (3) impact on daily activities and quality of life, (4) psychosocial modifiers, and (5) physiological features and biomarkers. By considering comorbidities, illness severity, psychosocial contributors, and potential biomarkers, the MDCP enables clinicians to develop a holistic understanding of the patient's condition. This multidimensional approach facilitates tailored, evidence-based treatment plans that address the biopsychosocial aspects of DGBI, ultimately enhancing symptom management and patient well-being. Furthermore, it highlights gaps in knowledge and stimulates targeted research into these highly prevalent disorders. This case-oriented educational review will evaluate three DGBIs – functional dyspepsia, irritable bowel syndrome, and chronic abdominal pain – using the MDCP approach.

Background and aims The functional gastrointestinal disorders (FGIDs) are extremely common conditions associated with a considerable personal, social and health economic burden. Managing FGIDs in clinical practice is challenging because of the uncertainty of symptom-based diagnosis, the high frequency of overlap between these conditions and the limited efficacy of available therapies. It has often been argued that successful drug development and management of FGIDs requires knowledge of the underlying pathophysiology. Numerous and highly variable candidate pathophysiological mechanisms have been implicated in the generation of FGID symptoms, but there is no current consensus on how to best define the relevance of these disturbances. Methods A group of international experts on FGIDs developed plausibility criteria that should be fulfilled by relevant pathophysiological mechanisms in FGIDs. Results Five criteria are proposed: (1) the presence of the abnormality in a subset of patients, (2) temporal association between proposed mechanism and symptom(s), (3) correlation between the level of impairment of the mechanism and symptom(s), (4) induction of the symptom(s) by provoking the pathophysiological abnormality in healthy subjects and (5) treatment response by a therapy specifically correcting the underlying disorder or congruent natural history of symptoms and dysfunction in the absence of specific therapy. Based on strength of evidence for these five criteria according to the Grading of Recommendations Assessment, Development and Evaluation system, a plausibility score can be calculated for each mechanism. Conclusion Evaluation of the strength of evidence for candidate pathophysiological abnormalities fulfilling these five plausibility criteria will help to identify the most relevant mechanisms to target for novel diagnostic approaches and for the development of new therapies.

Objective IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies. Design We conducted a GWA study (GWAS) of IBS in a general population sample of 11 326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls. Results One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein), showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31×10 −6 in a meta-analysis of all datasets. Several SNPs in this region are associated with cis effects on KDELR2 expression, and a trend for increased mucosal KDLER2 mRNA expression was observed in IBS cases compared with controls. Conclusions Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations.