Symptoms but not physiology differentiate functional dyspepsia with or without overlapping gastrointestinal disorders

Objectives: Functional dyspepsia, a disorder of gut-brain interaction (DGBI) 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. This study aimed 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 seven 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 (PAGI-SYM and LPDS ( P < 0.0001)) and psychological (anxiety ( P = 0.0014), depression ( P = 0.0017) and extraintestinal somatic symptoms ( P < 0.0001)) symptoms were more pronounced in FD with overlapping disorders, while all physiological parameters were similar. Patients with epigastric pain syndrome reported a milder symptom pattern compared to 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). Conclusion: The common overlap between FD, IBS and reflux is characterized by a high GI-specific, psychological and somatic symptom burden. In 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.