Glucuronidation and Enterohepatic Recirculation

β-glucuronidase produced by the microbiome can deconjugate xenobiotics that have already undergone glucuronidation by phase II enzymes, causing them to undergo enterohepatic recirculation rather than being eliminated in the feces.   Elmassry et al. (2021) found that males have higher levels of intestinal β-glucuronidase than females, and infants have higher levels than their mothers.  Malik et al. (2016) describe this process as it relates to estrogen, and mention that fiber can bind to bile acids and help to escort more of the toxins in them out of the body.  They also mention activated charcoal as being able to reduce enterohepatic recirculation.

I also found a study (Guo et al., 2017) supporting the idea that diet can be used to upregulate phase II pathways.  This was a rodent study, but they found dramatic effects on expression of half the phase II enzyme genes that they looked at.  They found that the uridine diphosphate-glucuronosyltransferase (Ugt) enzymes, known to be involved in the glucuronidation of both BPA and bile acids, were reduced under the restrictive diet and also the atherogenic diet.  Estrogen sulfotransferase was increased on the restrictive diet.  Other sulfotransferases were decreased on the atherogenic, high fructose, and EPA deficient diets.  Glutathione S-transferases were increased by the restrictive diet as well as by the atherogenic diet and the diet that was normal compared to the purified diet, and they were decreased by the EPA deficient diet.  While we can’t just generalize these results from rodents to humans, this study gives a good overview of the varied ways in which diet can interact with detoxification, and can help us to understand why someone might feel better on one diet compared to another. 

References:

Elmassry, M. M., Kim, S., & Busby, B. (2021). Predicting drug-metagenome interactions: Variation in the microbial β-glucuronidase level in the human gut metagenomes. PLoS ONE, 16(1), 1–21. 

Guo, Y., Cui, J. Y., Lu, H., & Klaassen, C. D. (2017). Effect of nine diets on mRNAs of phase-II conjugation enzymes in livers of mice. Xenobiotica, 47(8), 645–654. 

Malik, M. Y., Jaiswal, S., Sharma, A., Shukla, M., & Lal, J. (2016). Role of enterohepatic recirculation in drug disposition: cooperation and complications. Drug Metabolism Reviews, 48(2), 281–327.