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Breast milk represses UDP‐glucuronosyltransferase (UGT) 1A1 expression in the gastrointestinal tract, increasing the risk for severe hyperbilirubinemia and brain damage
Author(s) -
Fujiwara Ryoichi,
Chen Shujuan,
Tukey Robert H.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.850.12
Subject(s) - kernicterus , unconjugated hyperbilirubinemia , breast milk , jaundice , glucuronosyltransferase , medicine , bilirubin , gastrointestinal tract , breast feeding , endocrinology , gastroenterology , enzyme , physiology , pediatrics , chemistry , biochemistry , microsome
Infants develop physiological jaundice, which can be severe and cause irreversible brain damage, a physical property called kernicterus. Accumulating evidence indicates that breast‐fed infants have a higher risk for kernicterus than formula‐fed infants. However, the underlying mechanism linking severe hyperbilirubinemia to breast feeding has not yet been elucidated. Here we describe a new mechanism that places breast‐fed neonates at risk for developing kernicterus using recently developed humanized UDP‐glucuronosyltransferase 1 ( hUGT1 ) mice. Breast‐fed hUGT1 mice develop hyperbilirubinemia. In contrast, formula‐fed mice have significantly lower levels of serum bilirubin. Compared to breast‐fed neonates, formula‐fed mice have dramatically higher levels of UGT1A1 , the sole bilirubinconjugating enzyme, in the gastrointestinal tract. None of the formula fed mice develop severe hyperbilirubinemia or kernicterus. Furthermore, the oral treatment of neonatal hUGT1 mice with agents that activate NF‐kB results in induction of intestinal UGT1A1 . We are proposing that breast milk suppresses UGT1A1 expression in the GI by stimulating inhibition of the NF‐kB pathway. These findings indicate that intestinal control of UGT1A1 in neonatal children is sufficient in preventing developmentally induced hyperbilirubinemia and brain toxicity. (Supported by grants GM086713 and ES010337)