Lacticaseibacillus paracasei LP36 Alleviates Lipopolysaccharide-Induced Depression-like Behavior in Mice: A Serum Metabolomics Study
Abstract
Background/objectives: Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric condition for which current therapies remain inadequate. Probiotics acting on the microbiota-gut-brain axis are a promising preventive strategy, but their benefits are strain-specific. Here we examined whether Lacticaseibacillus paracasei LP36 alleviates lipopolysaccharide (LPS)-induced depression-like behavior in mice, and we characterized its metabolic actions using serum untargeted metabolomics.
Methods: Sixty male C57BL/6J mice were randomized into eight groups (58 completed the study and were analyzed) and received saline or LP36 (1 × 108, 1 × 109, or 1 × 1010 colony-forming units (CFU)/mL) by gavage for 28 days, with LPS (0.5 mg/kg, i.p.) or saline given during the last 10 days.
Results: LP36 pretreatment alleviated LPS-induced depression-like behavior in the sucrose preference, forced swimming, and tail suspension tests. Of 2867 annotated serum metabolites, 404 differed between the LPS and control groups, and 601 between the LP36 (1010)-treated and LPS groups. Among 180 shared differential metabolites, 172 (95.6%) changed in opposite directions, indicating that LP36 mainly reverses LPS-induced metabolic perturbations. KEGG enrichment localized these effects to lipid-related pathways, with lower relative signal intensities of polyunsaturated fatty acids and sphingolipids under LPS and higher relative signal intensities after LP36. In addition, the relative signal…
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