Background and aims-Altered intestinal permeability is a key pathogenetic factor of idiopathic bowel inflammation. We investigated in the rat if changes in the composition of the bowel flora can alter colonic permeability. Methods-A colonic segment was surgically excluded from faecal transit and brought out as a loop to the abdominal wall through two colostomies. The loop was used for colonisation with specific bacterial strains after eradication of the native flora with antibiotics. Lumen to blood clearance of dextran (molecular weight 70 000) and mannitol (molecular weight 182) was measured in rats recolonised with a single bacterial strain from rat colonic origin, and in control rats whose colonic loop was kept free of bacteria by antibiotics. Actual colonisation was confirmed by culture of segment eZuents. Results-Colonisation with Escherichia coli, Klebsiella pneumoniae, and Streptococcus viridans significantly increased lumen to blood clearance of mannitol. Colonisation with Lactobacillus brevis had the opposite eVect and reduced permeability to mannitol. Bacteroides fragilis did not induce significant changes. Permeability to dextran was not altered by any of the strains tested. Conclusions-Certain commensal bacteria can modify colonic wall permeability to luminal substances. (Gut 2001;48:503-507) Keywords: bacteria; dextran; intestinal permeability; mannitol; rat The colonic mucosal barrier is a complex physicochemical structure that separates the internal "milieu" from a polluted luminal environment. Barrier function ultimately depends on the integrity of the mucosa-from the endothelium to the epithelial cell lining-and the reactivity of dynamic defensive factors such as mucosal blood flow and epithelial secretions. A gel formed by the interaction of various mucosal secretions, including mucin glycoproteins, trefoil peptides, and surfactant phospholipids, comprises the mucus layer that covers the epithelium.

Commensal bacteria may participate in the pathogenesis of bowel inflammation. We studied the role of bacteria from the rat colonic flora on transmural inflammation induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). First, bacterial translocation to the colonic wall after induction of colitis was assessed by microbiological and histological methods. Second, rats with a colonic segment excluded from fecal transit were prepared for recolonization with preselected bacteria and used to test the effects of different species on inflammation (eicosanoid release, tissue myeloperoxidase) and damage (histology). Six strains (three aerobes and three anaerobes) were identified in colonic tissue 24 h after induction of colitis. Acridine staining showed bacteria in necrotic areas of the mucosa and invading the submucosa. Rats with excluded colon and sterile culture of luminal washings showed mild inflammation and low mucosal damage in response to TNBS. Rats colonized with anaerobes showed significantly higher eicosanoid release than rats colonized with aerobes only. Moreover, submucosal-lesions were mostly observed in rats with anaerobes. Our findings suggest that colonic anaerobes play a key role in transmural inflammation.

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A prospective study was performed to assess the value of differential quantitative blood cultures in the diagnosis of catheter-related sepsis when this condition is suspected on clinical grounds and to establish a reliable discriminative value for application without removal of the inserted catheter. A total of 107 central venous catheters from 64 patients were used for the study. Blood was obtained simultaneously through the suspected infected device and from a peripheral venipuncture. The catheter was removed and its tip cultured semiquantitatively. Catheter-related sepsis occurred in 17 patients. Using as cut-off value a colony count fourfold higher in blood drawn through the catheter than in simultaneously drawn peripheral blood, a sensitivity of 94%, specificity of 100% and positive predictive value of 100% were obtained. A single bacterial count greater than 100 cfu/ml in the quantitative culture of the catheter blood specimen in the presence of a positive qualitative peripheral blood culture of the same organism was also highly suggestive of catheter-related sepsis. Differential quantitative blood culture is a reliable method for the diagnosis of catheter-associated sepsis without catheter removal.

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