The long-term objective of this research is to increase our understanding of human milk beta-glucuronidase and its relationship to the neonatal metabolism of glucuronidated substrates. Conjugation with glucuronic acid (glucuronidation) is an important metabolic pathway for the clearance of endogenous compounds and xenobiotics. Deconjugation (deglucuronidation) with resulting decreased clearance can be equally important. Beta-Glucuronidase in human milk can cause such deconjugation, through limited data are available. Substrates of interest are those which undergo hepatic glucuronidation and are secreted into the intestine via the bile prior to excretion from the body in feces. During interstitial transit these glucuronides will be exposed to beta-glucuronidase in the interstitial lumen. Deconjugation caused by beta-glucuronidase facilitates the intestinal absorption of these substrates (enterohepatic circulation), thus delaying excretion from the body. In this proposal the specific glucuronidated substrate to be studied will be bilirubin. Two hypotheses will be tested: 1. Human milk beta-glucuronidase is a significant factor related to neonatal hyperbilirubinemia. 2. Human milk beta-glucuronidase activity varies among races and is one factor related to the interracial differences in hyperbilirubinemia. These hypotheses will be tested with data from two clinical protocols. In clinical protocol #1 three groups of human infants, each receiving a distinct diet, will be studied for the first three weeks of life. This study will take advantage of the recent discovery by the PI that casein hydrolysate formula is inhibitory to beta-glucuronidase. The three diets will differ in the amount of beta-glucuronidase present: human milk is rich in beta-glucuronidase, standard formula has negligible beta- glucuronidase, casein hydrolysate formula is inhibitory to beta- glucuronidase. Detailed studies of milk beta-glucuronidase activity will be made. Fecal beta-glucuronidase activity will be measured daily in the three groups. The relationship between beta-glucuronidase intake (diet) and output (feces) will be examined along with effects on neonatal jaundice. Fecal bile pigment profiles and total fecal bile pigment levels will be measured as a reflection of intraluminal beta- glucuronidase activity. Clinical protocol #1 will test hypotheses 1 above. In clinical protocol #2 White, Oriental and Black newborns who are exclusively fed human milk will be compared. beta-Glucuronidase levels in human milk and infant feces will be compared during the first week of life. This information plus fecal bile pigment studies will be related to levels of serum bilirubin at approximately 72 hours of age. Clinical protocol #2 will test hypothesis 2 above.
| Gourley, G R; Kreamer, B; Cohnen, M et al. (1999) Neonatal jaundice and diet. Arch Pediatr Adolesc Med 153:184-8 |
| Bancroft, J D; Kreamer, B; Gourley, G R (1998) Gilbert syndrome accelerates development of neonatal jaundice. J Pediatr 132:656-60 |
| Gourley, G R; Kreamer, B L; Cohnen, M (1997) Inhibition of beta-glucuronidase by casein hydrolysate formula. J Pediatr Gastroenterol Nutr 25:267-72 |
| Gourley, G R; Kreamer, B; Arend, R (1992) The effect of diet on feces and jaundice during the first 3 weeks of life. Gastroenterology 103:660-7 |
