The liver plays an important role in the digestion of dietary compounds due to the production of bile.
Bile is composed of water, conjugated bile acids, mucin, cholesterol, phospholipids, and anorganic salts and has a pH value of 7.1. In the gall bladder, mixed micelles are formed by these components 146, 147. In humans, the majority of bile acids is conjugated to glycine whereas there are mainly taurine-conjugates in mice 148. Upon stimulation by cholecystokinin (CCK), bile is secreted into the duodenum 86, 149. The bile forms micelles with dietary lipids and lipid soluble vitamins. This process is necessary for cleavage and absorption of dietary fat 86, 149–152.
Bile acids are water-soluble and amphipathic steroids. Primary bile acids, cholic acid (CA) and CDCA, which is converted to ?- and ?-muricholic acid (MCA) in rodents, are synthesized in liver hepatocytes from cholesterol via two different pathways: classical and acidic 86, 150, 151, 153. In the classical pathway cholesterol is directly converted to 7-hydroxycholesterol, whereas in the acidic pathway it is transformed via two intermediates. In both pathways, the rate limiting enzyme is cholesterol 7?-hydroxylase (Cyp7a1) 86, 149, 150. Bacterial modifications, including deconjugation, dehydroxylation, and dehydrogenation of primary bile acids, lead to the formation of 15 – 20 so called secondary bile acids 150.
As unconjugated bile acids are strongly cytotoxic, they are conjugated to taurine or glycine in the liver 86.Some intestinal bacteria, including Coriobacteriaceae and members of the genera Bacteroides, Clostridium, Lactobacillus, and Bifidobacterium are able to transform bile acids by various enzymes. Before transformation can take place, the bile acids have to be deconjugated which is mediated by microbial bile salt hydrolase (BSH) (Figure 4) 115, 154–156.
Hydroxysteroid dehydrogenases (HSDHs) can then epimerize various hydroxyl groups of bile acids via an oxo intermediate. This epimerization can be carried out by a single bacterial species (intraspecies) or in cooperation of different species (interspecies) 157. In bacteria, several bile acid inducible (bai) genes involved in bile acid dehydroxylation were found 154. Table 1 shows presence of BSH and HSDH genes in Coriobacteriaceae.