665 - Developmental Changes in Muricholic and Hyocholic Bile Acids in Human Infants

Publication Number: 1642.665

Naureen Memon, Goryeb Children's Hospital, Morristown, NJ, United States; Aimee Herdt, MidAtlantic Neonatology Associates, Morristown, NJ, United States; Elizabeth A. Eckman, MidAtlantic Neonatology Associates, Morristown, NJ, United States; Chris Lee, Biomedical Research Institute of New Jersey, Cedar Knolls, NJ, United States; Thomas Hegyi, Rutgers, Robert Wood Johnson Medical School, New Brunswick, NJ, United States; Mary Carayannopoulos, Rutgers, Robert Wood Johnson Medical School, Westfield, NJ, United States; Lauren Aleksunes, Rutgers University, Piscataway, NJ, United States; GRACE GUO, RUTGERS UNIV., PISCATAWAY, NJ, United States

Background: 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, such as muricholic acids (MCAs) and hyocholic acid (HCA), can be found in neonates. Recent studies have shown that these atypical BAs may be useful biomarkers for neonatal sepsis and pediatric/adult liver diseases. Currently, there is limited data on C-6 hydroxylated BA profiles in the perinatal period.

Objective: To systematically characterize both common BAs and C6-hydroxylated species in preterm and term infants and to longitudinally evaluate the dynamic changes in BA composition over time within a cohort of preterm infants.

Design/Methods: This was an observational study conducted in a single center NICU. Plasma samples were obtained during the first week of life from preterm (n=18) and term (n=7) infants. In a subset of preterm infants (n=5), longitudinal samples were additionally collected at 3 defined postnatal points. Twenty-six different BAs (Fig 1) were quantified by LC-MS/MS. Data were analyzed by unpaired two-tailed t-tests. Statistical significance was set at p < 0.05.

Results: Mean total BA levels were approximately two-fold higher in preterm infants than in term infants (49,543 ± 7,213 ng/mL vs 25,630 ± 4,630 ng/mL, p = 0.01). Across both groups, CA and CDCA (including their conjugates) represented the dominant species, together accounting for more than 87% of the total BA pool (Fig 2). DCA and LCA (including their conjugates) were higher in term compared to preterm infants (1,542 ± 898 ng/mL vs 308 ± 147 ng/mL, p < 0.01). Atypical BAs (MCA, HCA, and HDCA) were proportionally higher in preterm infants. In the subset of 5 preterm infants with serial samples, total plasma BA rose progressively over time (Fig 3). Despite this increase, the proportional composition of the BA pool remained largely stable. CA and CDCA (including their conjugates) consistently accounted for 87-93% of the total BAs. In contrast, MCAs declined from 11% to 6% of the pool.

Conclusion(s): BA concentrations and composition differed markedly between preterm and term infants, with preterm infants exhibiting higher total BA levels and a more hydrophilic profile. The substantial proportion of MCAs, the most hydrophilic BA, in preterm infants may reflect developmental adaptations in BA metabolism and warrants further exploration for potential therapeutic applications.

Figure 1. Plasma BA concentrations in preterm and term infants during the first week of life.
Boxplots show individual and grouped BA species- cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), α-muricholic acid (αMCA), β-muricholic acid (βMCA), ω-muricholic acid (ωMCA), hyocholic acid (HCA), hyodeoxycholic acid (HDCA), ursodeoxycholic acid (UDCA)- along with their glycine (G) or taurine (T) conjugates, measured in plasma collected within the first week of life in (A) preterm infants (n = 18) and (B) term infants (n = 7). Concentrations are expressed in ng/mL. Boxes represent interquartile ranges, horizontal lines indicate medians, and whiskers denote the 10th-90th percentiles. *HCAs were measured in a subset of patients: preterm (n=10), term (n=3)

Figure 2. Relative BA composition in preterm (PT) and term infants during the first week of life.
Pie charts illustrate the proportional distribution of BA subclasses in preterm (left) and term (right) infants. Percentages represent mean relative contributions within each group. Total measured BA concentrations (ng/mL) are shown below each pie chart. *HCAs were measured in a subset of patients: preterm (n=10), term (n=3).

Figure 3. Longitudinal changes in BA composition in preterm infants.
Pie charts illustrate the proportional distribution of BA subclasses in a subset of preterm infants (n = 5) obtained over time (DOL < 7, DOL 15-28, and DOL 32-60). Percentages represent mean relative contributions within each group. Total measured BA concentrations (ng/mL) are shown below each pie chart.