This study examines how intestinal bacteria from laboratory animals hydrolyze glycosidic bonds in compounds, with implications for toxicology and drug metabolism. The researchers characterized the bacterial flora of rats, mice, guinea pigs, and rabbits at different gastrointestinal sites and measured glycosidase enzyme activities from 50 strains representing six bacterial groups. Key findings include: rats and mice have much heavier bacterial colonization throughout their digestive tract compared to rabbits and guinea pigs (which resemble humans); Escherichia coli produces high β-glucuronidase activity, while enterococci produce high β-glucosidase; and strictly anaerobic bacteria (Bacteroides and bifidobacteria) contribute most to total enzymatic activity in the small intestine despite lower per-cell activity. The researchers calculated that rats and mice have 15 times greater β-glucuronidase activity in their small intestine than rabbits, suggesting that drug metabolism via bacterial enzymes occurs much more extensively in these commonly used laboratory animals than in humans. This difference has important implications for extrapolating toxicological findings from animals to humans.

Key findings

• Intestinal bacterial populations differ substantially between animal species, with rats and mice having denser colonization than rabbits, guinea pigs, or humans, particularly in the small intestine
• Different bacterial species produce distinct glycosidase enzyme profiles: E. coli dominates β-glucuronidase production while enterococci produce high β-glucosidase activity
• Strictly anaerobic bacteria (Bacteroides and bifidobacteria) contribute the majority of total glycosidase activity in the small intestine despite having lower per-cell enzyme levels
• β-glucuronidase activity in rat small intestine is approximately 15-fold higher than in rabbits, with minimal activity in humans, indicating greater bacterial-mediated drug metabolism in rodents