Polydeoxycholate in human and hamster feces: a major product of cholate metabolism.
Fecal bile acid excretion is one of the two major routes by which cholesterol is eliminated from the body, fecal cholesterol being the other. During their enterohepatic circulation, bile acids are secreted into the duodenum, pass down the jejunum and into the ileum where more than 95% is reabsorbed by the gut. Bile acids that escape reabsorption in the small intestine are metabolized by microorganisms in the large intestine. The major routes of metabolism are reported to be deconjugation, dehydroxylation, especially at the 7 alpha-hydroxy position, and dehydrogenation of the hydroxyl moieties. There are also some reports that saponifiable metabolites containing mostly deoxycholic acid form a major component of the bile acids found in human feces. We have identified a novel metabolite of cholic acid, 3 alpha-hydroxy polydeoxycholate, in both human and hamster feces that is the major constituent of these saponifiable metabolites. Furthermore, we have shown in hamsters that the animals that excreted more bile acid were excreting the additional bile acid as polydeoxycholate. As expected, there was a negative correlation between bile acid excretion in the feces and plasma cholesterol concentrations in these animals. We speculate that polydeoxycholate is formed in the lower gut of both humans and hamsters and that, by its formation, bile acid will be sequestered in an insoluble form, thus inhibiting its reabsorption by the gut. This process may help to reduce plasma cholesterol concentrations and coronary heart disease in humans.
Benson
G M
GM
SmithKline Beecham Pharmaceutical Research Limited, Welwyn, Hertfordshire, U.K.
Haskins
N J
NJ
Eckers
C
C
Moore
P J
PJ
Reid
D G
DG
Mitchell
R C
RC
Waghmare
S
S
Suckling
K E
KE
D000818:Animals; D000440:Butanols; D002725:Chloroform; D019826:Cholic Acid; D002793:Cholic Acids / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D006224:Cricetinae; D003840:Deoxycholic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D005243:Feces / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008647:Mesocricetus; D000432:Methanol; D011108:Polymers / Q000032:analysis* / Q000378:metabolism; D012995:Solubility; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014867:Water
D000440:Butanols; D002793:Cholic Acids; D011108:Polymers; D003840:Deoxycholic Acid; D014867:Water; C085677:3-hydroxy-polydeoxycholic acid; D002725:Chloroform; D019826:Cholic Acid; D000432:Methanol