Untargeted metabolomics elucidates the enhanced protective effects of blackberry juice fermented with Lacticaseibacillus paracasei on hypothalamic-pituitary-adrenal (HPA) axis neuronal dysfunction.

In this study, lactic acid bacteria (LAB) fermentation was employed to improve the neuroprotective characteristics of blackberry juice (BJ). The underlying mode of action of fermented (F) and unfermented (UF) BJs protecting against corticosterone (CORT)-induced neuronal injury was clarified by multiple techniques. The total viable count of Lacticaseibacillus paracasei PC18 reached 9.58 log CFU/mL at approximately 30 h fermentation. FBJ markedly increased PC12 cell viability and MMP, and alleviated ROS and cell death, compared to UFBJ. The exogenous apoptosis-related signaling pathways showed lowered Bax and elevated Bcl-2, BDNF, and CREB levels in CORT-injured cells, corroborating the neuroprotection of FBJ. Untargeted metabolomics, which identified 1757 metabolites in BJ groups, revealed that most differentially-accumulated metabolites (DAMs) were mainly associated with amino acid metabolism, biosynthesis of other secondary metabolites, nucleotide metabolism, and membrane transport. This study explored potential of BJ as probiotic carrier with enriched small neuroactive compounds to protect against neuronal dysfunction.