<i>Lactobacillus brevis</i> ZFM820 Attenuates LPS-Induced Inflammation via Biofilm Formation and Metabolic Reprogramming

Emerging evidence implicates lipopolysaccharide (LPS) embedded in the outer membrane of Gram-negative bacteria as a key mediator of intestinal inflammation. A preliminary study found that a potent <i>Lactobacillus brevis</i> strain named ZFM820 showed remarkable antibacterial activity against LPS-producing <i>Escherichia coli</i> compared to other lactic acid bacteria through an unexplored mechanism. This study systematically investigated the anti-LPS phenotypes, responsive factors, and mechanism of ZFM820. The alleviation activity on LPS-induced inflammation and oxidative stress was confirmed both in RAW264.7 cells and <i>C. elegans</i> models. The alleviation efficiencies of live bacteria, dead bacteria, and their cell-free fermentation supernatant were compared, and they present 2.68, 1.04, and 1.12-fold reduction of NO levels and 1.79, 1.07, and 1.15-fold reduction of O₂^-, respectively, suggesting that the protective effect was achieved via live bacteria. Further mechanical studies revealed that ZFM820 formed a biofilm barrier to physiochemically impede LPS permeation and triggered metabolic reprogramming by suppressing histone synthesis and activating glutathione biosynthesis to biologically enhance epithelial resistance. These findings provide evidence for the anti-LPS activity of ZFM820, offering an innovative horizon to understand the beneficial mechanism of <i>L. brevis</i>.