Meta-Analysis: Chronic Gastrointestinal Symptoms and Comorbidities in Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders

Patients with Ehlers-Danlos syndrome (EDS)/hypermobility spectrum disorders (HSD) report higher rates of chronic gastrointestinal (GI) symptoms, disorders of gut-brain interaction (DGBI), and extraintestinal comorbidities. We conducted a systematic review and meta-analysis to assess the prevalence of chronic GI symptoms and comorbid conditions in hEDS/HSD. Electronic databases were searched until December 2025 for studies reporting on chronic GI symptoms in hEDS/HSD patients. Pooled prevalence rates, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated using the random effects model. The final dataset of 19 studies included 17,455 hEDS/HSD patients and 1,677,465 controls. The odds of chronic GI symptoms were higher in patients with hEDS/HSD compared to controls (OR 4.29, 95% CI 3.1-6.0). 65.3% (95% CI 51.4-77.0) of hEDS/HSD patients reported at least one chronic GI symptom, with heartburn being the most common (34.7%, 95% CI 28.3-41.7). The prevalence of DGBI in hEDS/HSD patients was 44.2% (95% CI 23.9-66.6), with functional dysphagia the most common DGBI at 34.2% (95% CI 25.7-43.8). Gastroesophageal reflux disease was reported in 41.3% (95% CI 27.2-57.0). In hEDS/HSD patients, the most common extraintestinal comorbidity was chronic fatigue (49%, 95% CI 34.6-63.6), followed by migraine (38.2%, 95% CI 19.9-60.5), orthostatic intolerance (OI) (35.9%, 95% CI 26.6-46.4), fibromyalgia (27.9%, 95% CI 16.0-44.0) and postural orthostatic tachycardia syndrome (POTS) (21.9%, 95% CI 5.2-59.1). Overall, > 60% of hEDS/HSD patients report chronic GI symptoms. DGBI, co-morbidities, including POTS, were highly prevalent in hEDS/HSD patients. However, the quality of the evidence is low due to significant clinical heterogeneity observed in the analyses. While the associations may suggest a causal relationship, the results should be interpreted with caution.