ABSTRACT BACKGROUND: COPD is accepted to be a multicomponent disease with various comorbidities. The contribution of the gastrointestinal tract to the systemic manifestation of COPD has never been investigated. This metabolically active organ may experience recurring local oxygen deficits during daily life, leading to disturbed intestinal integrity in COPD patients. METHOD: 18 patients with moderate COPD (mean FEV1: 55+/-3%predicted) and 14 matched healthy controls were tested on two occasions, a baseline measurement at rest and, at another day, during the performance of activities of daily living (ADLs). To assess enterocyte damage, plasma intestinal fatty acid binding protein (IFABP) levels were determined, whereas urinary excretion of orally ingested sugar probes was measured using liquid chromatography and mass spectrometry to assess gastrointestinal permeability. RESULTS: Plasma IFABP concentrations were not different between COPD patients and healthy controls at rest. In contrast, 0-3h urinary lactulose/rhamnose and sucralose/erythritol ratios and 5-24h urinary sucralose/erythritol ratios were significantly higher in COPD patients compared to controls, indicating increased permeability of the small intestine and colon. Furthermore, the performance of ADLs led to significantly increased plasma IFABP concentrations in COPD patients but not in control subjects. In line, the intestinal permeability difference between COPD patients and controls was intensified. CONCLUSION: Besides an altered intestinal permeability in COPD patients at rest, performing ADLs led to enterocyte damage in addition to intestinal hyperpermeability in COPD patients but not in controls, indicating functional alteration in the gastrointestinal tract. Hence, intestinal compromise should be considered as a new component of the multisystem disorder COPD. CLINICAL TRIAL REGISTRATION: ISRCTN33686980.