Preterm infants are at high risk of developing cholestasis during the transitional period of physiologic immaturity; a time when infants are also increasingly susceptible to liver toxicity. Bile acid (BA) accumulation and other defects of BA metabolism have also been shown to occur during the early life period and may likely contribute to hepatic instability among neonates. As such, it remains essential to more clearly understand BA metabolism and the physiological role of BAs during development.
Developmental regulation of the bile acid (BA) pool has been documented across several species, including humans. Cholic acid (CA) and chenodeoxycholic acid (CDCA), and their taurine/glycine conjugated forms, are the predominant BA species in both adults and neonates. However, C-6 hydroxylated products of CDCA, also known as muricholic acids, can be found in neonates. Recent studies have shown that these atypical BA may be useful biomarkers for neonatal sepsis and pediatric/adult liver diseases. Currently, there is limited data on BA profiles in the perinatal period, and reference ranges for atypical BA are unavailable. Moreover, there is no data on perinatal expression of key BA synthesis enzymes, which may explain the presence of atypical BA in neonates.
We have several ongoing studies related to BA metabolism and it’s role in neonatal liver disease. For example, we are interested in the developmental changes in BA profiles, including atypical BAs in term and preterm infants. We are also characterizing RNA expression of major enzymes/transporters involved in BA synthesis and excretion into fetal livers.