Three measurable and modifiable enteric microbial biotransformations relevant to cancer prevention and treatment

Abstract

Interdisciplinary scientific evaluation of the human microbiota has identified three enteric microbial biotransformations of particular relevance for human health and well-being, especially cancer. Two biotransformations are counterproductive; one is productive. First, selective bacteria can reverse beneficial hepatic hydroxylation to produce toxic secondary bile acids, especially deoxycholic acid. Second, numerous bacterial species can reverse hepatic detoxification-in a sense, retoxify hormones and xeonobiotics-by deglucuronidation. Third, numerous enteric bacteria can effect a very positive biotransformation through the production of butyrate, a small chain fatty acid with anti-cancer activity. Each biotransformation is addressed in sequence for its relevance in representative gastrointestinal and extra-intestinal cancers. This is not a complete review of their connection with every type of cancer. The intent is to introduce the reader to clinically relevant microbial biochemistry plus the emerging evidence that links these to both carcinogenesis and treatment. Included is the evidence base to guide counseling for potentially helpful dietary adjustments.

Keywords: Microbiota; beta-glucuronidase; bile acids; butyrate; deoxycholic acid; small chain fatty acids.

Figure 1

The primary bile acids chenodeoxycholic acid (CDCA) and cholic acid (CA) are produced in the liver, stored in the gallbladder, and, when prompted, discharged into the small intestine. These support the digestion of fats, and 95% are reabsorbed in the distal ileum and returned to the liver via the enterohepatic circulation. These can also circulate to the entire body. Approximately 5% pass on to the large intestine, where they may be transformed into the potential toxins deoxycholic acid (DCA) and lithocholic acid (LCA). DCA is subject to uptake, systemic circulation, and return to the liver where it can be concentrated and stored in the gall bladder.

Figure 2

Hepatic glucuronidation of hormones and xenobiotics can be undone in the large intestine via bacterial beta-glucuronidase-mediated de-glucuronidation. The original products for disposal in the stool are then eligible for re-uptake and recirculation.

Figure 3

Ingested complex plant polysaccharides undergo significant digestion not in the small intestine, as expected, but instead undergo saccharolysis and fermentation in the large intestine. The mono- and dissacharides produced, as well as products of fermentation, are then transformed by subsets of anaerobic bacteria into butyrate, the predominant energy source for colonocytes. This is one example of cross-kingdom mutualism in the human intestinal tract.