From microbiota to metabolomics: how Bifidobacterium infantis YLGB-1496 shields neonates from necrotizing enterocolitis.

Bifidobacterium species are recognized as essential primary colonizers of the infant gastrointestinal tract and constitute a critical component of infant formula. Nevertheless, the precise mechanisms by which Bifidobacterium confers its protective effects against gut inflammation remain insufficiently elucidated. In an experimental model of Necrotizing Enterocolitis (NEC), we observed that human milk-derived Bifidobacterium longum subsp. infantis YLGB-1496 (GB1496) demonstrated a significant protective effect against mortality, intestinal damage, and TLR-4-mediated inflammatory responses in neonatal mice. Subsequent analyses of the intestinal microbiota indicated that oral administration of GB1496 during the preventive phase markedly increased the abundance of Lactobacillus and Bifidobacterium. Furthermore, serum untargeted metabolomics revealed significant alterations in the levels of tryptophan metabolites. Specific tryptophan metabolites, such as indole-3-acetic acid, L-formylkynurenine, and 5-hydroxyindole-3-acetic acid, were significantly enriched following GB1496 intervention, potentially activating the AHR-associated anti-inflammatory pathway as ligands. Correlation analysis indicates a potential association between GB1496-induced Bifidobacterium enrichment and enhanced intestinal tryptophan metabolism. The collective impact of GB1496 intervention has been demonstrated to engender an augmentation in Bifidobacterium abundance, a concomitant downregulation of inflammatory factors associated with the TLR-4 pathway, and an induction of alterations in serum tryptophan metabolites. It is evident that these combined effects contribute to its protective action against NEC.