*3.4.2.1 Bile acids (BAs)*

"Primary" bile acids are synthesized from cholesterol in the liver as cholic acid (CA) and chenodeoxycholic acid (CDCA). When the gallbladder is stimulated after a meal, BA flows into the duodenum and proceeds to the ileum to be actively reabsorbed, returning back to the liver through the portal bloodstream [112]. About 15% of BAs will escape ileum absorption and enter the colon, where the resident microbiota will transform them into secondary BAs (deoxycholic acid, DCA and lithocholic acid, LCA) that have pro and anticancer activity [112]. The enzyme responsible for this conversion is 7α/β hydroxysteroid dehydrogenase (HSDH), and it is produced specially by gram-positive Clostridium species such as *Clostridium scindens* [113].

Quantitative or qualitative BA pool perturbations may greatly affect several BA physiological body functions [113]. The consumption of a high-fat diet changes the gut microbiome and increases the level of DCA, that can promote carcinogenesis in colorectal and liver cancer [114, 115]. Pathways linking BAs to carcinogenesis involve the generation of ROS and reactive nitrogen species (RNS), which cause DNA damage, apoptose and epigenetic changes [112]. Moreover, BAs also exert strong antimicrobial activities, as they damage bacterial cell membranes, contributing to changes in gut microbiota (**Figure 3**). These mechanisms can also be secondary to environmental stimuli (particularly in the context of obesity) and their relationships with human cancer have been recognized as critical in gastrointestinal tract, prostate and breast tissues [116–118].

There are some publications covering changes in the fecal BA profile in canine chronic inflammatory enteropathy and extrahepatic congenital portosystemic shunts, but not in carcinogenesis [119–121].
