Lithocholic acid intestinal microflora

Some dietary factors can also change the bile acid species and, by doing so, alter cholesterol absorption. The liver synthesizes the primary bile acids, cholic and chenodeoxycholic acid. Bacteria in the intestine can convert some of the primary bile acids into secondary bile acids, producing deoxycholic from cholic acid and lithocholic from chenodeoxycholic acid. When certain dietary components alter the intestinal microflora, the rate of secondary bile... 

Several mechanisms may contribute to the association of meat with colon cancer. The heterocyclic amines and polycyclic aromatic hydrocarbons present in cooked meat are metabolized, in the body, to mutagens that may condense with DNA to form adducts. If the adduct occurs at a vital base, and if the adduct is not promptly repaired, cancer may result. Another possible mechanism is related to the enhanced excretion of bile salts into the intestines that occurs with a high-fat diet. In brief, the increased amount of bile salts (with a high-fat diet) that reaches the large intestines is metabolized by the gut microflora to an increased amount of modified bile salts. Specifically, lithocholic acid and deoxycholic acid are formed. These modified bile salts are thought to contribute to the conversion of a normal gut cell to a cancer cell. Recent studies suggest that chronic exposure of gut cells to these modified bile salts may result in chronic activation of protein kinase C and chronic... 

The intestinal microflora of man and animals can biotransform bile acids into a number of different metabolites. Normal human feces may contain more than 20 different bile acids which have been formed from the primary bile acids, cholic acid and chenodeoxycholic acid [1-5], Known microbial biotransformations of these bile acids include the hydrolysis of bile acid conjugates yielding free bile acids, oxidation of hydroxyl groups at C-3, C-6, C-7 and C-12 and reduction of oxo groups to give epimeric hydroxy bile acids. In addition, certain members of the intestinal microflora la- and 7j8-dehydroxylate primary bile acids yielding deoxycholic acid and lithocholic acid (Fig. 1). Moreover, 3-sulfated bile acids are converted into a variety of different metabolites by the intestinal microflora [6,7]. 

Huijghebaert et al. [23] isolated a bile salt sulfatase-producing strain designated, Clostridium S, from rat feces. This bacterium hydrolyzed the 3-sulfates of lithocholic acid, chenodeoxycholic acid, deoxycholic acid and cholic acid but not the 7-or 12-monosulfates. Sulfatase activity required the 3-sulfate group to be in the equatorial position. A free C-24 or C-26 carboxyl group was also required for sulfatase activity in whole cells of this bacterium. The 3-sulfate of cholesterol, Cj,-and Cji-steroids were not hydrolyzed by Clostridium S, [24]. Nevertheless, C,9- and C2]-steroid sulfates are hydrolyzed in the gut by microbial activity suggesting that the intestinal microflora may contain bacteria with steroid sulfatases possessing different substrate specificities. However, it should be noted that enzyme substrate specificity studies carried out in whole cells may reflect both cell wall permeability and enzyme specificity. 

C-labelled lithocholic acid sulphates, 27, found in both human and animal bile30,31, have been synthesized in a one-step32 sulphonation procedure (equation 11) to study the metabolic processes caused by human intestinal microflora and to make possible the identification of new mutagenic/carcinogenic products. Fecal bile lithocholic acid enhances liver and colon tumorigenesis. 

The positive results of treatment of cholesterol gallstones with chenodeoxycholic acid (3a,7a-dihydroxy-53-cholan-24-oic acid) (CDA) and its epimer ursodeoxycholic acid (3a,73-dihydroxy-53-cholan-24-oic acid) (UDA) are well known. In the colon these bile acids are mainly 7a-dehydroxylated by intestinal microflora into lithocholic acid (3a-monohydroxy-53-cholan-24-oic acid) (LCA), whose toxicity at the hepatic level has been demonstrated in different higher animals. 

---