Changes in Pre- and Post-Treatment Gut Microbiota and Metabolites in Neonates With Hyperbilirubinemia

Neonatal jaundice affects up to 60% of newborns, with pathological cases frequently associated with impaired bilirubin metabolism and gut microbiota dysbiosis. Although evidence implicates gut microbiota in bilirubin metabolism, the precise mechanisms remain incompletely characterized. This study investigated treatment-associated changes in gut microbiota composition, fecal metabolites, and liver function in neonates with hyperbilirubinemia.

A total of forty-two neonates diagnosed with hyperbilirubinemia were recruited. Fecal samples were collected pre- and post-treatment. Gut microbiota composition was analyzed via 16S rRNA gene sequencing, while fecal metabolites were profiled using untargeted metabolomics. Liver function parameters, including serum bilirubin levels, were measured. Statistical analyses encompassed alpha/beta diversity assessments, Spearman correlation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment.

Post-treatment gut microbial diversity decreased significantly, marked by increased abundance of Streptococcus thermophilus and Rothia and reduced levels of Pseudomonas and Staphylococcus. Key altered metabolites included 9,11-methane-epoxy PGF1α, prostaglandin E2 isopropyl ester, and 7-methylthioheptyl glucosinolate. Notably, Streptococcus thermophilus abundance inversely correlated with 7-methylthioheptyl glucosinolate but positively correlated with 9,11-methane-epoxy PGF1α and prostaglandin E2 isopropyl ester. Total bilirubin levels decreased significantly post-treatment, alongside improvements in other liver function markers.

This study demonstrates significant treatment-associated shifts in gut microbiota and metabolites in hyperbilirubinemic neonates, suggesting microbial dysbiosis may contribute to altered bilirubin metabolism. These findings highlight the potential of early microbiome-targeted interventions for managing neonatal jaundice and identify candidate therapeutic targets and biomarkers.