title: Large intestine permeability is increased in patients with compensated liver cirrhosis.
abstract: Intestinal barrier dysfunction, facilitating translocation of bacteria and bacterial products, plays an important role in the pathophysiology of liver cirrhosis and its complications. Increased intestinal permeability has been found in patients with liver cirrhosis, but data on small and large intestine permeability and tight junctions (TJs) in patients with compensated cirrhosis are scarce. We aimed to investigate both small and large intestine permeability in patients with stable compensated cirrhosis compared with healthy controls and evaluated the expression of TJ proteins in mucosal biopsies at duodenal and sigmoid level. Intestinal permeability was assessed in 26 patients with compensated cirrhosis and 27 matched controls using a multisugar test. Duodenal and sigmoid biopsies were available from a subgroup for analyses of gene transcription and expression of key TJ proteins by qRT-PCR and ELISA, respectively. Median 0-5-h urinary sucrose excretion and lactulose/rhamnose ratio were comparable between patients with compensated cirrhosis and controls, whereas 5-24-h urinary sucralose/erythritol ratio was increased in these patients. Downregulation of gene transcription was found for claudin-3 in duodenal biopsies and claudin-4 in sigmoid biopsies, and at the protein level occludin expression was significantly increased in both duodenal and sigmoid biopsies. This study shows that gastroduodenal and small intestine permeability are not altered, whereas large intestine permeability is increased in patients with stable compensated cirrhosis. Only limited alterations were found regarding the expression of TJ proteins in both the small and large intestine.
authors.affiliation: Div. of Gastroenterology-Hepatology, Dept. of Internal Medicine, Maastricht Univ. Medical Center, PO Box 5800, 6202 AZ Maastricht, the Netherlands. k.pijls@maastrichtuniversity.nl.
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: Pijls
authors.forename: Ger H
authors.initials: GH
authors.lastname: Koek
authors.forename: Elhaseen E
authors.initials: EE
authors.lastname: Elamin
authors.forename: Hanne
authors.initials: H
authors.lastname: de Vries
authors.forename: Ad A M
authors.initials: AA
authors.lastname: Masclee
authors.forename: Daisy M A E
authors.initials: DM
authors.lastname: Jonkers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D062506:Claudin-4 / Q000378:metabolism; D012809:Colon, Sigmoid / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism; D004724:Endoscopy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007420:Intestine, Large / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D062793:Occludin / Q000378:metabolism; D010539:Permeability; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D062725:Tight Junction Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D062506:Claudin-4; D062793:Occludin; D062725:Tight Junction Proteins
keywords: complications; intestinal epithelial barrier; liver cirrhosis; permeability; tight junctions