Exploring the Anti-Inflammatory Potential of Lacticaseibacillus paracasei Postbiotics: Mechanistic Insights and Functional Components

The anti-inflammatory properties of postbiotics have garnered significant attention. However, the functional components of postbiotics remain inadequately understood due to its diversity and complexity. In this study, we discovered that the cell-free supernatants (CFSs) of Lacticaseibacillus paracasei K56 (K56) exhibited significant anti-inflammatory properties. Non-targeted metabolomic analysis of the chemical composition of K56 CFSs revealed a predominant presence of lipids, amino acids and peptides, and organic acids. Compared to strains lacking anti-inflammatory activity, K56 CFSs were enriched with potential anti-inflammatory compounds. Notably, malic acid (MA) and decanedioic acid (DA) have been shown to effectively suppress inflammation in RAW264.7 cells.In zebrafish exposed to a high-fat diet, our observations indicated that intervention with K56 CFSs effectively mitigated hepatic and intestinal inflammation. Furthermore, DA and MA effectively alleviated dextran sulfate induced ulcerative colitis. RNA sequencing analysis revealed that the ameliorative effects of DA and MA were associated with their regulation of the IL-17 signaling pathway. Additionally, MA and DA were not only constituents of the postbiotics produced by Lacticaseibacillus but were also widespread among various probiotic strains. Collectively, these findings suggested that MA and DA may play a crucial role in the anti-inflammatory properties of the K56 postbiotic.