The Effect of Gut Bacteria on Primary Bile Acid Fermentation: A Pathway for Liver Disease and Colon Cancer

It is known that colorectal cancer has two main key risk factors: genetic predisposition and environmental remaining factors such as diet and gut microbiota composition. Bile acids (BA) are highly effective gastrointestinal detergents that promote digestion of lipidic nutrients and is involve in the maintenance of gut microbiome structure. Furthermore, some bacterial species were identified capable of metabolism host BAs, resulting in formation secondary toxic metabolites related to colon cancer and liver diseases. Meanwhile, some genes were observed to be significantly more abundant in metagenomes of C. scindens from colorectal cancer subjects, in fact, the gene baiE encodes the rate limiting enzyme in secondary BA (SBA) fermentation pathway which represents a key target for loss-of-function gene and treatment. Genetic knockouts of genes in the BA deconjugation pathway have yet to be reported, for this reason, researchers of The Sterolbiome Laboratory of University of Illinois have been focused on achieving successful gene edition of C. scindens baiE with major focus on understand mechanics of BA and steroid metabolism by gut bacteria. To achieve this, shuttle vector with resistance genes and baiE gene will be design and integrate to C. scindens ATCC 35704. Disruption of baiE in C. scindes will be confirmed through BA biotransformation assay comparison to wild-type strain, and the baiE chromosomal region will be sequenced at the Keck Center for Biotechnology UIUC. Disruption of the baiE gene represents an opportunity for inhibition of SBA synthesis or/and a baiE represents a potential target for drug treatment to reduce the risk of colon and liver cancer