Effects of enteric microbial overgrowth on small intestinal ultrastructure in the rat.

The ultrastructural effects of bacterial proliferation in the upper gastrointestinal tract induced by intraperitoneal injections of mecamylamine HCl were investigated in rats. We found increased populations of nonspecific enteric bacteria in the lumen of the upper small intestine and ultrastructural abnormalities in the absorptive epithelial cells, including increased numbers of lysosomal vacular structures, fused microvilli and dilated endoplasmic reticulum. The bacteria did not penetrate into the damaged mucosal cells and so actual cytoplasmic infiltration is apparently not required in order to cause these ultrastructural changes. The alterations were not merely due to the pharmacologic agent we used, mecamylamine, since rats with subnormal numbers of enteric bacteria in the upper small intestine, whether subjected to the course of the drug or not, did not display the ultrastructural changes noted above. Concomitant with increased numbers of enteric bacteria in the small intestine, there were increased concentrations of deconjugated bile salts and decreased absorption of glucose. These findings are compatible with the following hypothetical sequence of pathogenesis: mecamylamine leads to intestinal stasis leads to bacterial overgrowth leads to deconjugation of the bile salts leads to ultrastructural alterations.