Profile of Urinary Bile Acids in Infants and Children: Developmental Pattern of Excretion of Unsaturated Ketonic Bile Acids and 7 β-Hydroxylated Bile Acids

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Abstract

ABSTRACT

Unusual bile acids, such as unsaturated ketonic and 7β-hydroxylated bile acids, have been detected in urine early in life. To elucidate the normal profiles of usual and unusual urinary bile acids in the neonatal and pediatric periods, we measured the concentrations of 28 kinds in urine from normal newborns, infants, and children by gas chromatography-mass spectrometry. The mean total bile acid/Cr ratio in 7-d-old infants was significantly higher than in subjects of other age groups (birth, 2-4 mo, 5-7 mo, 11-12 mo, 2-3 y, 9-14 y, and adult) (p < 0.05). Relatively large amounts of unusual bile acids were detected during infancy, especially during the period up to 1 mo of age. At that time, 1β,3α,7α,12α-tetrahydroxy-5β-cholan-24-oic, 7α,12α-dihydroxy-3-oxo-5β-chol-1-en-24-oic, and 7α,12α-dihydroxy-3-oxo-4-cholen-24-oic acids were predominant among the unusual urinary bile acids present. Moreover, the levels of 3α,7β,12α-trihydroxy-5β-cholan-24-oic acid increased significantly after 2-4 mo of age. These results indicate that bile acid synthesis and metabolism in the liver of developing infants are significantly different from that occurring in the liver of adults. Significant amounts of urinary isomerized 7β-hydroxylated bile acids were detected after late infancy, probably because of changes in the intestinal bacterial flora response to a change in nutrition. We describe, for the first time, evidence of the epimerization of the 7α-hydroxyl group of cholic acid, which may be unique to human development.

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