(M1030-04-26) Impact of Host Physiological and Pathological Conditions on the Activity of Gut Microbial Beta-Glucuronidases (GUS) toward Hydrolysis of Flavonoids-Glucoronides

Purpose: The purpose of this study is to determine the impact of host physiological and pathological conditions on the activity of gut microbial beta-glucuronidases (GUS) towards hydrolysis of flavonoid-glucuronides.

Methods: Fecal S9 fractions were prepared using feces collected from different types of rats at different ages with different genders. Also, Fecal S9 prepared from F344 rats at three different ages (i.e., 5, 9, and 16 weeks) and different inflammatory conditions treated with DSS or anti-inflammatory agent XCHT. Additionally, fecal S9 from genetically modified PRIC rats, which spontaneously have inflammation in the colon, was also tested. Baicalin, wogonoside, and luteolin-glucuronide were used as the substrates. A Waters Acquity Ultra performance liquid chromatography (UPLC) system was used to quantify the metabolite baicalein to analyze the rate of the reaction of the enzymes. The rates were compared by obtaining enzymes through S9 fractions to confirm microbiota ability to hydrolyze the glucuronide and release of the parent compounds.

Results: The data shows that microbial activity was higher at elder age. Fecal S9 from Pirc rats has lower activity and anti-inflammatory agent XCHT can increase gut microbial glucuronidases (GUS) activity. The results depicted that age had an impact on hydrolysis of the compound baicalin into its parent compound and this method was best suited to determine the rate of hydrolysis. The p< 0.05 making the results statistically significant. The wild type enzymes had a clear increase in Km and Vmax. While PRIC enzymes and enzymes treated with DSS and XCHT had a clear difference in rates, but the Km and Vmax did not increase significantly.

Conclusion: The data shows that microbial gut microbial glucuronidase (GUS) activity was higher at elder age. Fecal S9 from Pirc rats has lower activity and anti-inflammatory agent XCHT can increase microbial GUS activity.