Changes in the Gut Microbiota of Neonates with Hyperbilirubinemia Reaching Phototherapy Thresholds

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Purpose: The gut microbiota plays a crucial role in bilirubin metabolism in neonates. The phototherapy threshold assesses the need for clinical intervention in neonatal hyperbilirubinemia (NH). This study aimed to investigate gut microbiota alterations in neonates with NH meeting the phototherapy threshold. Patients and Methods: A total of 75 neonates with NH who met the phototherapy threshold (NH group), and 67 healthy neonates (control group) were included. Fecal samples were collected within one hour before initiating phototherapy for 16S rRNA gene sequencing and bioinformatic analysis. Results: In contrast to healthy controls, the NH group showed significantly higher Shannon ( p < 0.001) and abundance-based coverage estimator ( p < 0.05) indices, as well as significant differences in both unweighted and weighted UniFrac values ( p < 0.001 for each). In addition, linear discriminant analysis effect size revealed significant taxonomic shifts in the gut microbiota of the NH group at multiple levels, including phylum, class, order, family, and genus. Among the key differential genera, the abundance of Streptococcus ( p < 0.001) was significantly reduced, whereas Escherichia ( p < 0.001) and Klebsiella ( p < 0.001) were markedly enriched. Conclusion: Neonates meeting the phototherapy threshold exhibit altered gut microbiota composition, characterized by increased diversity, richness, and an elevated abundance of opportunistic pathogenic genera. These results offer valuable preliminary insights into the gut microbiome changes associated with NH requiring phototherapy. Keywords: neonatal hyperbilirubinemia, phototherapy threshold, gut microbiota, neonate, 16S rRNA

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