Thanks to Lostfalco's popular
The Microbiome and Brain Enhancementthread
http://www.longecity...in-enhancement/I have found a paper that is much easier to read than the 1st one.
Bile acids/salts are cholesterol-derived host metabolites that play a role in several host processes (Fig. 2). Their
principal functions are to aid in fat adsorption and prevent small intestinal bacterial overgrowth. Both these functions can be explained by the fact that bile acids are surfactants (not detergents), with a hydrophilic taurine or glycine group covalently bound to a hydrophobic steroid (predominantly a C24 structure (Russell 2003))-derived moiety that is wholly derived from cholesterol. This surfactant nature allows them to associate with fat molecules to form micelles, which are ultimately absorbed by the host, thus facilitating fat metabolism. Additionally, being a surfactant allows them to be antimicrobial also, as they can disrupt the plasma membrane of the bacteria, causing them to lyse and die;
thus in a niche where food is plentiful, bile helps to prevent the bacteria in the small intestine from overgrowing and becoming a health issue. A secondary role for bile involves regulating the host's cholesterol levels, on a typical day, ∼0.5 g of this steroid is used to synthesise bile acids in hepatocytes and accounts for 90% of the cholesterol usage (Russell 2003). Once the hormonal signal has been sent to the gall bladder, the
bile acids are excreted into the small intestine, where they interact with the dietary lipids and fat-soluble vitamins. These complexes are eventually reabsorbed in the terminal ileum; this process is part of the enterohepatic circulation that ensures that 95% of the bile acids are recovered from the gut. The remaining 5% that escapes this pathway enters the large intestine, where it becomes available for metabolism by bacteria. Interestingly, the gut bacteria have evolved several enzymes capable of modifying the primary bile acids such as the taurine- and glycine-conjugated cholic and chenodeoxycholic acids and removing the taurine and glycine parts of the molecules to produce secondary bile salts, such as cholic, lithocholic and deoxycholic acids. While some of these secondary bile acids are excreted in the faeces, a significant proportion are passively absorbed and returned to the liver. These secondary bile acids then enter the enterohepatic circulation and the general bile metabolite pool. The bacterial enzymes responsible for the deconjugation of either taurine or glycine are collectively known as bile salt hydrolases (BSHs), choloylglycine hydrolases or bile acid hydrolases (EC 3.5.1.24) and catalyse the hydrolytic removal of taurine or glycine from the corresponding primary bile acids. However, as with many gut functions, the diversity and abundance of BSHs are highly variable as are their substrate ranges (Jones et al. 2008). Additionally, studies on germ-free rodents (i.e. sterile or gnotobiotic) have shown that the bile pool is significantly and dramatically altered in other non-liver or non-gut compartments too, e.g. heart tissue (Fig. 3), which begs the question of the significance of having a specific BSH profile in the gut and the host's own physiology.
Bile acids interact at an endocrinological level via three major signalling mechanisms, as ligands for the G-protein-coupled receptor TGR5, activators of the MAPK pathways and activators of the nuclear hormone receptors such as farnesoid X receptor α (FXRα; NR1H4). While the primary bile acids are of significant interest as they have been shown to regulate lipid, energy and glucose metabolism, the
secondary bile acids can also interact with these receptors. However, the availability of the secondary bile acids is not as tightly controlled since it is driven by the variable and dynamic diversity and expression of BSHs in the gut. Hence, the gut microbiota can be thought of as another environmental factor controlling an up-and-coming endocrine factor that is not stable and influenced by diet and medications..."
http://joe.endocrino.../218/3/R37.long So:
bile does prevent bacterial overgrowth,
most is recovered from the gut,
but about 5% is not and is turned into Secondary Bile Salts in the large intestine.
A significant portion are passively absorbed and returned to the liver.
ie: They enter the general bile metabolite pool where they will affect the endocrine system to some degree.
So research on the effects of LCA s warranted:
LCA can substitute for vitamin D in the elevation of serum calcium in vitamin D-deficient rats by the mobilization of calcium from bone.
But it is hepatotoxic, a tumour promoter, and CYP3A4 is up regulated to protect against its effects!
Refs:
http://www.pnas.org/.../10006.full.pdfhttp://www.ncbi.nlm..../pubmed/1641875http://www.researchg...polymerase_betahttp://www.pubfacts....ne-specific-VDRhttp://en.wikipedia.org/wiki/CYP3A4Thx xEva!
I will now look at TUDCA
