Multi-omics reveals the role of Bifidobacterium animalis with the potential to reshape the bile acid pool in neonatal jaundice

Neonatal jaundice (NJ), affecting 60-80% of newborns, risks neurotoxicity in severe cases. Although gut microbiota dysbiosis is known to influence bilirubin and bile acid (BA) metabolism, key microbial mechanisms remain incompletely understood. Through a multi-omics analysis of 120 neonates, we identified the key bacteria of moderate-to-severe jaundice and discovered the correlations between gut phages, bacteria, and BA in NJ. Moderate-to-severe NJ exhibited distinct gut dysbiosis, characterized by increased Streptococcus and Escherichia, while depleted Bifidobacterium animalis. Therapeutic intervention reversed this imbalance, suppressing pathogens while restoring B. animalis. Virome profiling revealed distinct group-specific phage patterns (e.g., Streptococcus phage dominance in GBS group, Enterobacteria phage in NJ) and significant phage-bacteria covariance, encompassing both potential lytic and symbiotic interactions. Structural modeling quantified interactions: phages indirectly modulated BA via microbiota restructuring, whereas B. animalis directly regulated BA metabolism. Functionally, B. animalis bile salt hydrolase (BSH) activity was downregulated in active NJ and recovered post-treatment. In vitro assays confirmed its BA-remodeling capacity, reducing total BA while enhancing deconjugation (increased deoxycholic acid). Animal experiments suggested that B. animalis might ameliorate jaundice and liver damage, potentially via Cyp7a1/Cyp7b1-mediated BA metabolic regulation. Together, these findings reveal a multi-faceted interaction involving phages, bacteria, and BA in NJ, and highlight B. animalis as a promising therapeutic candidate.