Bile salts bacterial deconjugation

In the intestinal tract, a substantial portion of the primary bile salts is deconjugated by bacterial enzymes and reduced (dehydroxylated), whereby... 

Intestinal bacteria deconjugate and dehydroxylate the bile salts, removing the glycine and taurine residues and the hydroxyl group at position 7. The bile salts that lack a hydroxyl group at position 7 are called secondary bile salts. The deconjugated and dehydroxylated bile salts are less soluble and, therefore, less readily resorbed from the intestinal lumen than the bile salts that have not been subjected to bacterial... 

When bile salts are deconjugated by abnormal bacterial proliferation in the small bowel (40), yielding free or unconjugated bile salts with a pK of 4-6, they are quickly absorbed by nonionic diffusion in the jejunum so that intraluminal bile salt concentration may be insufficient for efficient fat absorption and steatorrhea may result (41). 

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. ... 

Improper milieu Abnormal motility secondary to diabetes, scleroderma, hyperthyroidism Bacterial overgrowth - blind loops (deconjugation of bile salts), diverticula Zollinger-Ellison syndrome (low duodenal pH)... 

Small bowel disease Mucosal lesion e.g. Celiac disease Tropical sprue Bacterial overgrowth deconjugation of bile salts) Parasites e.g. Giardia Intestinal resection Ileal disease - Crohn s Abetalipoproteinemia Drugs... 

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. 

Fig. 34.13. Structures of the primary and secondary bUe salts. Primary bile salts form conjugates with taurine or glycine in the hver. After secretion into the intestine, they may be deconjugated and dehydroxylated by the bacterial flora, forming secondary bile salts. Note that dehydroxylation occurs at position 7, forming the deoxy family of bUe salts.

The serum bile salt pattern is altered in patients with bacterial proliferation in the small intestinal content (stagnant loop or blind loop syndrome). Bacterial deconjugation of bile salts in the lumen of the small intestine per-... 

It is quite probable that enterolith formation in man is a consequence of stasis and bacterial proliferation in the intestine. Microbial enzymes deconjugate bile salts, which raise their pK to a value of about 6, so that much of the free bile acid is un-ionized and precipitates at the / H of intestinal content. When microbial enzymes also convert cholic acid to deoxycholic acid, the latter compound forms choleic acids, which have an even higher pKa and thus precipitate more readily. 

Neomycin is a polybasic, poorly absorbed antibiotic which forms insoluble precipitates with bile salts (99). It lowers serum cholesterol concentrations in man (100-102) and chickens (99) and increases fecal bile acid excretion. It inhibits the hepatotoxic effects of lithocholic acid ingestion in chickens (99) and prevents bacterial conversion of cholate to deoxycho-late (103). Neomycin, 6-12 g/day, induces a malabsorption syndrome, with mucosal changes similar to those of sprue (104). Bile salt metabolism is thus affected in at least three ways by neomycin (1) a binding effect similar to that of cholestyramine, (2) suppression of deconjugation and secondary bile formation caused by antimicrobial properties, and (3) possible impairment of absorption of bile salts by intestinal mucosa. The first probably accounts for most of the increased fecal excretion of bile salts. 

Studies with radioactive glycocholate or taurocholate demonstrated a virtual absence of the enterohepatic circulation of bile acids in patients with jejunotransversocolostomy (77). The small amount of absorbed bile acids contained some deconjugated cholate and deoxycholate (which had been reconjugated in the liver), indicating a rapid bacterial action during an apparently fast intestinal passage. Under these conditions, steatorrhea is apparently not solely due to bile salt deficiency induced impairment of micelle formation, but reduced absorptive area may play an important contributory role. No direct measurement of bile acid synthesis by fecal determination has been performed in this condition. 

In the normal individual the bile acids remain conjugated until they reach the colon, where they may be deconjugated by bacterial enzymes. If because of changes in the bacterial flora deconjugation occurs in the higher portion of the intestine, most of the free bile salts are rapidly reabsorbed, reconjugated, and partly excreted in the feces. Clearly, severe liver disease interferes with the complete conjugation of the bile salt pool. 

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