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Effects of enteric microbial overgrowth on small intestinal ultrastructure in the rat
Abstract:
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.
Insights
Mecamylamine HCl causes bacterial overgrowth in the upper small intestine, leading to ultrastructural damage in absorptive cells. This damage occurs without bacterial invasion and is linked to altered bile salts and reduced glucose absorption.
Area of Science:
- Gastroenterology
- Microbiology
- Pharmacology
Background:
- Bacterial proliferation in the upper gastrointestinal tract can impact host physiology.
- Mecamylamine HCl is known to affect gastrointestinal motility.
Purpose of the Study:
- To investigate the ultrastructural effects of mecamylamine HCl-induced bacterial proliferation in the rat upper gastrointestinal tract.
- To elucidate the role of bacterial overgrowth in drug-induced gastrointestinal changes.
Main Methods:
- Intraperitoneal injections of mecamylamine HCl in rats.
- Ultrastructural analysis of the upper small intestine.
- Quantification of enteric bacteria and bile salt concentrations.
- Assessment of glucose absorption.
Main Results:
- Mecamylamine HCl induced significant bacterial overgrowth in the upper small intestine.
- Ultrastructural abnormalities observed in absorptive epithelial cells included lysosomal structures, fused microvilli, and dilated endoplasmic reticulum.
- Increased deconjugated bile salts and decreased glucose absorption were noted.
- Damage was dependent on bacterial presence, not solely the drug.
Conclusions:
- Bacterial overgrowth, not direct drug toxicity, causes the observed ultrastructural changes.
- A proposed pathogenesis involves mecamylamine-induced stasis, leading to bacterial overgrowth, bile salt deconjugation, and subsequent cellular alterations.
- These findings highlight the impact of gut microbiota on drug-induced gastrointestinal pathology.