Bile acids deconjugation

One recent report showed increased bile acid deconjugation (demonstrated by " C-glycocholic acid breath test) by bacterial overgrowth in the jejunum after treatment of healthy volunteers or patients with gastric ulcer for 5 weeks with 20 mg of omeprazole daily which normalized after tetracycline treatment [63]. Increased steatorrhea has also been claimed in this study but is poorly documented by the semiquantitative " C-triolein breath test [63] and is in contradiction to the negative finding of another study which measured 72 h of fat excretion quantitatively after treatment with 40 mg of omeprazole daily [48]. 

A portion of the primary bile acids in the intestine is subjected to further changes by the activity of the intestinal bacteria. These include deconjugation and 7a-dehydroxylation, which produce the secondary bile acids, deoxycholic acid and hthocholic acid. 

Bile acids and salts have been found to enhance the absorption of both calcium and vitamin D hence, to increase calcium absorption both directly and indirectly (3,37). However, the ability of some dietary fibers such as lignin and pectin to absorb conjugated and deconjugated bile salts onto their surfaces to be excreted in the feces (a mechanism credited to the hypocholesterolemic effect of some dietary fibers) may result in an overall decrease in calcium absorption from the gastrointestinal tract (7,33,38-40). 

Bile acids within the enterohepatic circulation that undergo absorption in the terminal ileum encounter a relatively low number of species and population of bacteria and return to the liver in portal blood relatively unchanged. However, the approximately 5% of the bile-acid pool that enters the colon provides substrate for the extensive microbial population that deconjugate and oxidise hydroxyl groups leading to formation of the secondary bile acids deoxycholic and lithocholic acids that are the major bile acids in faeces. 

These deconjugated secondary bile acids are lipophilic and are believed to passively diffuse across the colon and enter the blood supply for return to the liver. Little is known of the mechanism, although in ASBT knockout mice there is an increase in OSTa/OSTp mRNA within the proximal colon.This could simply reflect reduced bile-acid uptake in the terminal ileum and a response to increased bile-acid levels entering the colon. 

Alternative potential strategies for reduction of mucosal secondary bile acid exposure are to target deconjugation of glycine/taurine bile salts by bacterial bile salt hydrolases and/or bacterial 7-dehydroxylation of primary bile acids to secondary bile acids. Sequestration of bile acids in the intestinal lumen using probiotic bacteria has also been proposed as an area for future research. ... 

Acid suppression is probably responsible for deconjugation of bile acids in the upper GI tract and hence oesophageal exposure to free bile acids. 

Abdominal surgery, radiation therapy Loss of absorptive surface Bypass Nutrient unavailability, deconjugation of bile acids Disturbed solubilization of lipids, decreased formation of micelles Short-bowel syndrome Enteroenteric fistual Bacterial overgrowth Loss of bile acids... 

Chromatography.—Considerable attention is being paid to chromatographic methods for the separation and recognition of bile acids and their derivatives. The analysis (g.l.c.) of mixtures of bile acids and their conjugates is reported to be simplified by direct conversion into heptafluorobutyrate derivatives, which occurs with simultaneous deconjugation.The carboxyl function is apparently converted into its volatile mixed cholanyl-heptafluorobutyryl anhydride. Ethyl-dimethylsilyl ethers of bile acid ethyl esters are also reported to be suitable for... 

The secondary bile acids result from the activity of anaerobic intestinal microorganisms in the ileum, caecum and colon, (s. fig. 3.3) Deconjugation, with the subsequent release of free bile acids, is a prerequisite for these reactions. This is followed by 7a-dehydroxylation of cholic acid and chenodeoxycholic acid to yield deoxy-cholic acid and lithocholic acid, respectively. 7a-de-hydrogenation and oxidation of chenodeoxycholic acid also yield ketolithocholic acid ... 

The gut microflora metabolize the bile acids produced by the human host. Their enzymes catalyze the deconjugation of the bile acids, that is, removal of the taurine and glycine groups. These enzymes also catalyze dehydroxylation, converting cholic acid to deoxycholic acid. Gut bacteria convert bile acids to compounds that appear to be carcinogenic and possibly contribxite to cancer of the colon. 

Secondary bile adds Products of deconjugated and reduced primary acids. Bacteria in the intestine remove the 7a-hydroxyl group, leaving the secondary bile acids. 

Bile salts/acids are synthesized in the liver, stored and concentrated in the gallbladder, and secreted into the intestine where they may undergo deconjugation and reduction by intestinal bacteria to produce secondary bile acids (see Figure 31-1). Once formed in the liver, the bile salts/acids are... 

Around one-quarter of the bile acid conjugates reaching the ileum have the amino acid moiety removed by the action of bacterial enzymes. A decon-jugating enzyme, choloylglycine hydrolase (EC 3.5.1.24) has been isolated from clostridial bacteria (Nl) and is used in methods for the analysis of bile acids. The majority of deconjugated bile acids are reabsorbed and return to the liver, where they are efficiently reconjugated with glycine or taurine (V7). 

Deconjugation of bile acids may become excessive when bacterial overgrowth occurs in the small intestine. This condition is referred to as the stagnant loop or blind loop syndrome and is characterized by diarrhea, often accompanied by steatorrhea because of a decrease in the effective concentration of conjugated bile salts and a reduction in the fat-absorptive capacity of the small intestine. 

To deconjugate bile acids for further analysis, particularly by gas-liquid chromatography, different methods are required for the hydrolysis of the peptide bonds in glycine and taurine conjugates than for hydrolysis of the ester sulfate and glucuronide bonds. Glycine and taurine may be removed by either alkaline or enzymatic hydrolysis (Rll). Alkaline hydrolysis is often... 

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