Pathogenesis of Mucosal Injury in the Blind Loop Syndrome

Abstract

A B S T R A C T The effect of intestinal bacterial overgrowth on brush border hydrolases and brush border glycoproteins was studied in nonoperated control rats, control rats with surgically introduced jejunal selfemptying blind loops, and rats with surgically introduced jejunal self-filling blind loops. Data were analyzed from blind loop segments, segments above and below the blind loops, and three corresponding segments in the nonoperated controls. Rats with selffilling blind loops had significantly greater fat excretion than controls and exhibited significantly lower conjugated:free bile salt ratios in all three segments. Maltase, sucrase, and lactase activities were significantly reduced in homogenates and isolated brush borders from the self-filling blind loop, but alkaline phosphatase was not affected. The relative degradation rate of homogenate and brush border glycoproteins was assessed by a double-isotope technique involving the injection of D-[6-3H]glucosamine 3 h and D-[U-14C]glucosamine 19 h before sacrifice, and recorded as a 3H: 14C ratio. The relative degradation rate in both homogenate and brush border fractions was significantly greater in most segments from rats with selffilling blind loops. In the upper and blind loop segments from rats with self-filling blind loops, the 3H:14C ratios were higher in the brush border membrane than in the corresponding homogenates, indicating that the increased rates of degradation primarily involve membrane glycoproteins. Incorporation of D-[6-3H]glucosamine by brush border glycoproteins was not reduced in rats with self-filling blind loops, suggesting that glycoprotein synthesis was not affected. Polyacrylamide gel electrophoresis of brush border glycoproteins from the contaminated segments indicated that the large molecular weight glycoproteins,

Effect of Secreted Bacteroides Proteases on Human Intestinal Brush Border Hydrolases

“…Similar changes have been demonstrated in human bacterial overgrowth syndromes (6,7). Several hypotheses explain the mechanism of the bowel mucosal damage, such as direct damage by bacteria (1)(2)(3)(4) or their secreted products, or changes in the luminal environment-e.g., effects of secondary bile acids (deoxycholic) with inhibition or solubilization of surface enzymes (8)(9)(10).…”

“…These include morphologic as well as enzymatic changes. Variations in the levels of brush border hydrolases in rats-e.g., sucrase, maltase, lactase, and alkaline phosphatase-have been evaluated most extensively (1,2,4,5). Similar changes have been demonstrated in human bacterial overgrowth syndromes (6,7).…”

“…Inhibitors were added as described in Table III (14,(33)(34)(35)(36) (14,38), whereas lactobacilli and E. coli are more dependent on vitamin B12 for growth (39). Jonas et al (4) have shown in experimental blind loop syndrome that a protease is elaborated that releases maltase from the brush border. This enzyme activity was most associated with B. fragilis, C. perfringens, and Streptococcus fecalis.…”

“…30303. 314 malabsorption. In animals, alterations of the mucosal surface membrane have been well documented (1)(2)(3)(4)(5). These include morphologic as well as enzymatic changes.…”

“…Recently Jonas et al (1,4) studied the pathogenesis of mucosal injury in the experimental blind loop syndrome in rats. They found that sonicated extracts of some bacteria cultured from the blind loops possess protease(s) that released, but did not destroy, brush border maltase activity.…”