Consequences of bile salt biotransformations by intestinal bacteria

Taurocholic acid metabolism by gut microbes and colon cancer

“…have evolved a multi-gene bile acid inducible operon capable of bile acid 7a-dehydroxylation of CA and CDCA and 7b-dehydroxylation of UDCA. 37,38,43 While the proximal explanation of this metabolic capacity is that the bile acid 7a/b-dehydroxylation pathway yields a net 2 electron reduction, the ultimate explanation might relate to production of a toxic, antimicrobial compound. 44,45 In addition, the fact that secondary bile acids (DCA, LCA and derivatives) are high affinity ligands to several host nuclear and G-coupled protein receptors suggests perhaps these metabolites are involved in interkingdom signaling.…”

“…To date, organisms that express BSH are not capable of converting CA to deoxycholic acid (DCA). 37,38 Likewise, organisms capable of producing DCA and LCA from host primary bile acids lack BSH and are incapable of converting conjugated primary bile acids such as TCA to DCA without the presence of BSH expressing taxa capable of converting TCA to free CA. 39,40 To survive in the gut environment, microorganisms have to contend with numerous host selection pressures, particularly anti-microbial agents such as lectins, defensins, and bile acids.…”

“…44,45 In addition, the fact that secondary bile acids (DCA, LCA and derivatives) are high affinity ligands to several host nuclear and G-coupled protein receptors suggests perhaps these metabolites are involved in interkingdom signaling. 19,37,38 During enterohepatic circulation, secondary bile acids are produced in the cecum and colon and returned to the liver by passive diffusion through the gut epithelium into the portal circulation. 39 Evidence is emerging that as animal-based diets stimulate more bile input into the gut the levels of DCA-producing bacteria increase.…”

“…The detergent nature of bile acids lead to membrane damage, collapse of proton motive force, and oxidative stress and DNA damage, resulting in top-down selection pressure on gut microbiome structure. 37 Microbes have evolved resistance mechanisms such as expression of HSDH capable of producing iso-bile acids (3b-hydroxy) or ursobile acids (7b-hydroxy) that are less toxic. 41,42 Indeed, the therapeutic use of ursodeoxycholic acid (UDCA) (3a,7b-dihydroxy-5b-cholan-24-oic acid) is due to its hydrophilicity, it is able to dilute out toxic secondary bile acids and render the bile acid pool less damaging to the host.…”

Gut microbial metabolites in health and disease

“…The important topic of bile salt metabolism is introduced by Ridlon et al 4 who provide an overview of the complex interplay between synthesis and conjugation by the host, and de-conjugation together with conversion of primary to secondary bile salts by gut bacteria. More specifically, in a second article, Ridlon et al 5 propose mechanisms by which microbial metabolism of taurocholate (whose formation is favored by diets high in animal protein) may promote colorectal cancer, through sulfide formation from taurine and via the tumor-promoting activity of the secondary bile acid deoxycholate.…”