Modulation of colonic barrier function by the composition of the commensal flora in the rat

Abstract

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 effluents.

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 effect 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.

Figure 1

Lumen to blood clearance of dextran five hours after administration of the labelled probe into the excluded colonic segment of controls (n=10) and rats recolonised with a single bacterial strain (Sv, Streptococcus viridans, n=6; Kp, Klebsiella pneumoniae, n=6; Ec, Escherichia coli, n=7; Bf, Bacteroides fragilis, n=7; and Lb, Lactobacillus brevis, n=9). Clearance is expressed as a percentage of the administered dose that accumulated in the intravascular space and normalised by length of the excluded colonic segment. Values are mean (SEM). No significant differences were found.

Figure 2

Lumen to blood clearance of mannitol in controls (n=10) and in rats recolonised with a single bacterial strain (Streptococcus viridans, n=6; Klebsiella pneumoniae, n=6; Escherichia coli, n=7). Clearance is expressed as a percentage of the administered dose that accumulated in the extracellular space and normalised by length of the colonic segment. Values are mean (SEM). *p<0.05 compared with controls at same time point.

Figure 3

Lumen to blood clearance of mannitol in controls (n=10) and in rats recolonised with a single bacterial strain (Bacteroides fragilis, n=7; Lactobacillus brevis, n=9). Values are mean (SEM). *p<0.05 compared with controls at same time point.

Figure 4

Lumen to blood clearance of ⁵¹Cr-EDTA in controls (n=8) and in rats recolonised with Escherichia coli (n=5). *p<0.05 compared with controls at same time point.