Symptoms but Not Physiology Differentiate Functional Dyspepsia With or Without Overlapping Gastrointestinal Disorders

Abstract

Introduction: Functional dyspepsia (FD), a disorder of gut-brain interaction defined by Rome IV criteria, overlaps frequently with irritable bowel syndrome (IBS) and reflux symptoms. Overlapping gastrointestinal (GI) disorders are associated with more psychological comorbidities and decreased quality of life, but data on physiological parameters in overlapping syndromes are scarce. The aim of this study was to evaluate the impact of overlapping disorders and FD subtypes on psychological and GI symptoms, as well as relevant physiological outcomes.

Methods: In total, 202 patients with predominant Rome IV FD symptoms and overlapping IBS and/or reflux were pooled from 7 studies conducted at University Hospitals Leuven. GI and psychological symptoms, as well as GI-related quality of life were recorded. Physiological measurements included salivary cortisol, gastric emptying, systemic and duodenal immune activation, and duodenal permeability.

Results: GI (Patient Assessment of Upper GI Symptom Severity and Leuven Postprandial Distress Scale [ P < 0.0001]) and psychological (anxiety [ P = 0.0014], depression [ P = 0.0017] and extraintestinal somatic symptoms [ P < 0.0001]) were more pronounced in FD with overlapping disorders, whereas all physiological parameters were similar. Patients with epigastric pain syndrome reported a milder symptom pattern compared with other FD subtypes, with similar physiological alterations. Duodenal eosinophils were associated with anxiety in FD, independent of overlapping GI disorders or subtype ( P = 0.043).

Discussion: The common overlap between FD, IBS, and reflux is characterized by a high GI-specific, psychological, and somatic symptom burden. By contrast, key pathophysiological parameters were not different between FD with and without overlapping disorders or between FD subtypes. Central integration of multiple GI manifestations rather than more severely impaired peripheral alterations is more likely to explain the high symptom burden in overlapping disorders.

Keywords: anxiety; disorders of gut-brain interaction; eosinophils; epigastric pain syndrome; functional dyspepsia; overlapping gastrointestinal disorders; psychological comorbidities.