Dynamic relationships between bilirubin concentrations and the gut microbiota in the neonatal period: A pilot prospective cohort study.

Importance: Understanding the dynamic interplay between gut microbiota development and bilirubin metabolism may provide new insights into the pathophysiology of neonatal jaundice. Identifying microbial taxa associated with bilirubin fluctuations could help inform early prediction and microbiota-targeted interventions for hyperbilirubinemia. Objective: To investigate the correlation between dynamic changes in the gut microbiota and bilirubin concentrations during the neonatal period. Methods: Bilirubin concentrations were monitored daily throughout the neonatal period. Fecal samples were collected from neonates on days 1, 3, 7, 14, 21, and 28 after birth. The composition of the gut microbiome was assessed by 16S rRNA gene amplicon sequencing of the fecal samples. Within-subject, same-day associations between transcutaneous bilirubin (TcB) and genus-level abundance were quantified using a repeated-measures correlation. Results: Thirty neonates were included in the final analysis. Among the top-30 genera, six exhibited false discovery rate significant, same-day within-subject associations with TcB under the repeated-measures correlation framework (|rrm| ≥0.30). Changes in the abundances of the genera Streptococcus (r rm = +0.416, 95% confidence interval [CI] 0.272-0.543, P = 2.084 × 10-7; P-adj = 3.126 × 10-6) and Rothia (r rm = +0.340, 95% CI 0.187-0.476; P = 3.134 × 10-5; P-adj = 1.567 × 10-4) were positively correlated with bilirubin concentrations throughout the neonatal period. In complementary cross-sectional analyses centered on meconium, additional genus-bilirubin correlations were identified for TcB measured on postnatal days 3-7 and for the neonatal TcB peak, with multiplicity controlled separately for each endpoint. Interpretation: A correlation was found between dynamic changes in the gut microbiome and bilirubin concentrations during the neonatal period. The identified genera might be potential markers or targets for intervention for neonatal jaundice.