Epimerization of chenodeoxycholic acid to ursodeoxycholic acid by Clostridium baratii isolated from human feces

Abstract

Ursodeoxycholic acid-producing bacteria are of clinical and industrial interest due to the multiple beneficial effects of this bile acid on human health. This work reports the first isolation of 7-epimerizing bacteria from feces of a healthy volunteer, on the basis of their capacity to epimerize the primary bile acid, chenodeoxycholic acid, to ursodeoxycholic acid. Five isolates were found to be active starting from unconjugated chenodeoxycholic acid and its tauro-conjugated homologue, but none of these strains could epimerize the glyco-conjugated form. Biochemical testing and 16S ribosomal DNA sequencing converged to show that all five isolates were closely related to Clostridium baratii (99% sequence similarity), suggesting that this bacterial species could be responsible at least partially, for this bioconversion in the human gut.

Contribution of the 7β-hydroxysteroid dehydrogenase from Ruminococcus gnavus N53 to ursodeoxycholic acid formation in the human colon

“…PO1-3 ( 34 ), and Cl. baratii ( 26 ), all from the human intestine, and in the soil bacterium Cl. absonum ( 36,(39)(40)(41).…”

“…UDCA is produced from chenodeoxycholic acid (CDCA; 3 ␣ , 7 ␣ -dihydroxy-5 ␤ -cholan-24-oic acid) by successive reactions catalyzed by 7 ␣ -and 7 ␤ -hydroxysteroid dehydrogenases (HSDH) of intestinal bacteria (24)(25)(26), with 7-oxo-lithocholic acid (7-oxo-LCA; 3 ␣ -hydroxy-7oxo-5 ␤ -cholan-24-oic acid) as an intermediate ( 27 ) ( Fig. 1 ).…”

“…PO1-3 ( 34 ), and Cl. baratii ( 26 ) have been shown to be NADP(H)-dependent. The optimum pH range of the enzyme was similar to already known 7 ␤ -HSDHs: an acidic range for the forward reaction producing UDCA and an alkaline range for the reverse reaction producing 7-oxo-LCA (33)(34)(35) ( Fig.…”

Microbial modulation of cardiovascular disease

“…In fact, the vast majority of genetic and biochemical studies have focused primarily on substrains Clostridium scindens , in which the bile acid inducible (bai) operon has been well characterized 149 . In addition to deconjugation and 7α and 7β dehydoxylation reactions, gut microbes can oxidize or epimerize bile acids via several distinct enzymes of the hydroxysteroid dehydrogenase (HSDH) family 150,151 . HSDH activity has been confirmed in a diverse variety of bacteria, including Bacteroides , Clostridium , Escherichia , Egghertella , Eubacterium , Peptostreptococcus and Ruminococcus .…”

Clostridium scindens baiCD and baiH genes encode stereo-specific 7α/7β-hydroxy-3-oxo-Δ4-cholenoic acid oxidoreductases☆

“…UDCA is an important therapeutic agent for the treatment of cholestatic liver disease (15)(16)(17)(18) and its administration has been suggested to prevent colon cancer (19)(20)(21). UDCA is capable of being directly 7β-dehydroxylated to LCA (22) as well as epimerized to CDCA and then 7α-dehydroxylated to LCA (23)(24)(25). However, genes involved in the 7β-dehydroxylation of UDCA have not yet been identified.…”