title: Increased small intestinal permeability in ulcerative colitis: rather genetic than environmental and a risk factor for extensive disease?
abstract: BACKGROUND
  A disturbed epithelial barrier could play a pivotal role in ulcerative colitis (UC). We performed a family-based study analyzing in vivo gastrointestinal permeability in patients with UC, their healthy relatives, spouses, and controls.
  
  
  METHODS
  In total, 89 patients with UC in remission, 35 first-degree relatives (UC-R), 24 nonrelated spouses (UC-NR), and 99 healthy controls (HC) were studied. Permeability was assessed by a sugar-drink test using sucrose (gastroduodenal permeability), lactulose/mannitol (intestinal permeability), and sucralose (colonic permeability). Data were correlated with clinical characteristics including medical treatment.
  
  
  RESULTS
  Increased intestinal permeability was detected significantly more often in UC patients in remission (25/89, 28.1%) compared with HC (6/99, 6.1%; P < 0.001). Similar results were obtained in UC-R (7/35, 20.0%; P = 0.01 compared with HC) regardless of sharing the same household with the patients or not. No difference was found between UC-NR (3/24, 12.5%) and HC. Notably, in UC patients increased intestinal permeability was found in 12/28 patients (42.9%) with pancolitis, 7/30 (23.3%) patients with left-sided colitis, and in 2/19 (10.5%) patients with proctitis (P = 0.04). Gastroduodenal and colonic permeability were similar in all groups. Among patients on azathioprine, increased intestinal permeability was only seen in 1/18 (5.6%) patients. In contrast, in 24/70 (34.3%) patients without azathioprine, an increased intestinal permeability was found (P = 0.005).
  
  
  CONCLUSIONS
  An increased intestinal but not colonic permeability was found in UC patients in clinical remission that could mark a new risk factor for extensive disease location. Similar findings in healthy relatives but not spouses suggest that this barrier defect is genetically determined.
authors.affiliation: Department of Gastroenterology, Hepatology & Endocrinology, Charité, Campus Mitte, Berlin, Germany. carsten.buening@charite.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Büning
authors.forename: Nora
authors.initials: N
authors.lastname: Geissler
authors.forename: Matthias
authors.initials: M
authors.lastname: Prager
authors.forename: Andreas
authors.initials: A
authors.lastname: Sturm
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Baumgart
authors.forename: Janine
authors.initials: J
authors.lastname: Büttner
authors.forename: Sabine
authors.initials: S
authors.lastname: Bühner
authors.forename: Verena
authors.initials: V
authors.lastname: Haas
authors.forename: Herbert
authors.initials: H
authors.lastname: Lochs
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007408:Intestinal Absorption / Q000235:genetics*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use; D010539:Permeability; D011349:Proctitis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D012074:Remission Induction; D012307:Risk Factors; D018454:Spouses; D013395:Sucrose / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D007166:Immunosuppressive Agents; D013395:Sucrose; D015122:Mercaptopurine; D001379:Azathioprine