Bacterial Enzymes

A wide range of enzyme activities capable of generating potentially carcinogenic metabolites in the colon are associated with the gut microbiota, including b-glucuronidase b-glucosidase, nitrate- and nitro-reductase. These are usually assayed in fecal suspensions and appear to be present in many bacterial types. Of these enzymes, b-glucuronidase has been the most extensively investigated as a biomarker of CRC risk. It should be noted that these factors are associated with the generation of carcinogens and promoters and do not have a direct link with tumors.

b-Glucuronidase

Many carcinogenic compounds are metabolized in the liver and then conjugated to glucuronic acid before being excreted via the bile into the small intestine. In the colon bacterial b-glucuronidase can hydrolyze the conjugates, releasing the parent compound or its activated, hepatic metabolite.

The activity of b-glucuronidase in the colon can alter the likelihood of tumor induction in animal models of CRC. The use of a b-glucuronidase inhibitor administered in conjunction with the carcinogen azoxymethane (which undergoes activation and conjugation in the liver) significantly reduces the number of tumors formed in the rat colon, indicating that microbiota b-glucuronidase has a role in tumor induction. Metabolic epidemiological studies have shown that populations at high risk of CRC have high levels of fecal b-glucuronidase activity. Furthermore, fecal b-glucuronidase activity in colon cancer patients is significantly higher than in healthy controls.

The activity of b-glucuronidase is influenced by diet. High risk diets for CRC have consistently been shown to increase b-glucuronidase activity relative to low risk diets. Furthermore, various types of fiber decrease the activity of b-glucuronidase in rats.

Although it represents a simple reproducible marker, evidence for a role for b-glucuronidase in human CRC is indirect and is remote from the final endpoint (tumors).

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