title: Expression of tight-junction proteins in human proximal small intestinal mucosa before and after Roux-en-Y gastric bypass surgery.
abstract: BACKGROUND
  Increased permeability and uptake of proinflammatory bacterial endotoxins from gut microbiota has been suggested as a mechanism for obesity-associated chronic inflammation that causes obesity-associated insulin resistance. We hypothesized that intestinal barrier function may be restored after Roux-en-Y gastric bypass (RYGB) surgery and thereby contribute to decreased inflammation. The objective of this study was to investigate levels of the permeability-regulating tight-junction proteins in human small intestinal mucosa before and after RYGB surgery.
  
  
  METHODS
  Paired intraindividual jejunal mucosa samples were retrieved at the time of surgery and 6 to 8 months after surgery. Mucosal cell surface area was calculated by histomorphometry. Mucosal samples were analyzed by proteomics to find patterns of protein regulations. Based on these findings further analyses were performed by Western blotting. Ussing chambers were used to analyze permeability in the retrieved mucosal samples.
  
  
  RESULTS
  Mucosal surface area was significantly decreased after surgery. Global protein expression analysis showed a significant increase in the cytokeratin-8 (Ck8), which was confirmed by Western blotting. Further analyses showed a significant increase in claudin-3 and -4 expression after surgery, whereas occludin and zonula occludens-1 levels were decreased. Expressions of claudin-1, -2, -5 and vinculin were unchanged. Ussing chamber experiments revealed a linear correlation between the epithelial electrical resistance and claudin-3 protein expression.
  
  
  CONCLUSIONS
  Several alterations were found in the rerouted small intestine after surgery, indicating a decreased jejunal mucosal surface area and decreased paracellular permeability. These changes could contribute to decreased uptake of luminal microbiota-derived inflammatory mediators such as endotoxins after RYGB.
authors.affiliation: Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: anna.casselbrant@gastro.gu.se.
authors.forename: Anna
authors.initials: A
authors.lastname: Casselbrant
authors.affiliation: Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Elias
authors.affiliation: Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Fändriks
authors.affiliation: Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Ville
authors.initials: V
authors.lastname: Wallenius
mesh_terms: D000328:Adult; D000368:Aged; D017097:Electric Impedance; D005260:Female; D015390:Gastric Bypass; D015391:Gastroplasty; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D010535:Laparoscopy; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000378:metabolism / Q000601:surgery*; D011182:Postoperative Care; D011300:Preoperative Care; D040901:Proteomics; D062725:Tight Junction Proteins / Q000378:metabolism*
chemical_list: D062725:Tight Junction Proteins
keywords: Epithelial resistance; Obesity; Roux-en-Y gastric bypass; Small intestine; Tight junction