330 - Fecal bile acid profiles in preterm infants <1250g birth weight with and without faltering growth

Publication Number: 3318.330

Andrew M. Beverstock, Baylor College of Medicine, Houston, TX, United States; Monica Narvaez Rivas, Cincinnati Children's Hospital, Cincinnati, OH, United States; Laura Gollins, Texas Children's Hospital, Houston, TX, United States; Emily Sabatini, Baylor College of Medicine, Houston, TX, United States; Joseph Hagan, Baylor College of Medicine, Houston, TX, United States; Lindsay F. Holzapfel, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States; Kenneth D R. Setchell, Cincinnati Children's Hospital, Cincinnati, OH, United States; Geoffrey A. Preidis, Baylor College of Medicine, Houston, TX, United States; Amy B. Hair, Baylor College of Medicine, Houston, TX, United States

Background: Bile acids (BA) are synthesized in the liver, secreted in bile and are critical to lipid absorption in the small intestine. The bile acid pool size is maintained by an efficient enterohepatic circulation, but 5% daily is lost in feces. In previous studies of preterm infants, we found that increased fecal bile salt hydrolase (BSH) gene expression and unconjugated BAs, the products of microbial BSH activity, were associated with improved growth velocity. Reduced BSH activity may reflect delayed gut microbial colonization. Analysis of early fecal BA profiles may predict faltering growth and inform targeted nutritional interventions.

Objective: To assess whether fecal BA products of the BSH enzyme correlate with growth outcomes in non-cholestatic preterm infants.

Design/Methods: We conducted an IRB-approved nested case-control study of preterm infants with birth weight (BW) < 1250g, born between 24 and 32 weeks gestation. Infants with cholestasis (any conjugated bilirubin >1mg/dL) or major congenital anomalies were excluded. Infants were categorized into faltering growth (n=15), defined as a weight/age Z-score decline >1.2 from birth to 34 weeks postmenstrual age (PMA), and adequate growth (n=15). Infants were 1:1 matched based on gestational age, BW and SNAPPE-II score (illness severity). Stool samples were collected at 14, 21 and 28 postnatal days and at 34 weeks PMA. Fecal BA composition was determined by tandem mass spectroscopy. The groups were compared using mixed effects linear modeling.

Results: 30 infants were included (Table 1). The fecal BA composition over time is shown (Fig 1). There was an increase over time in the proportion of unconjugated BAs like cholic acid (CA) and a decrease in the proportion of conjugated BAs such as taurolithocholic acid and tauroursodeoxycholic acid (TUDCA). Unconjugated BAs increased over time in both groups (p < 0.001), but the difference between groups was not significantly (p=0.289), potentially due to sample size limitations in this small pilot study (Fig 2).

Conclusion(s): Our findings indicate increased BSH activity with increasing PMA: there was increased CA and reduced TLCA and TUDCA with increasing infant maturity. Both TLCA and TUDCA are BSH targets, suggesting increased BSH activity with increasing PMA. We did not detect statistically significant differences in bile acid proportions between the groups but we had a small sample size. Our findings underscore the need for a larger, adequately powered study to detect more subtle differences in BA profiles across multiple timepoints, and incorporating direct measurements of BSH expression.

Table 1
Baseline patient demographics in the adequate and faltering growth groups (n=15 in each group). 1 Median (IQR), 2 n (%)

Figure 1
Fecal bile acid profiles in preterm infants with adequate and faltering growth at each timepoint. The profile shows evolution with an increasing proportion of unconjugated bile acids over time with a large increase in the proportion of cholic acid with increasing postmenstrual age.

Figure 2
Box and whisker plot of unconjugated bile acids as a proportion of the total fecal bile acid pool at each timepoint in each group. Figure shows minimum, 1st, 2nd and 3rd quartiles and maximum. X indicates mean value in group.