Fermented casein with Lactobacillus gasseri KML39 alleviates systemic inflammation interacting with the...

This study investigated the preventive effects of fermented casein with Lactobacillus gasseri KML39 (FSC) on systemic inflammation through modulation of the gut-brain-microbiome axis in a dextran sulfate sodium (DSS)-induced colitis mouse model. Lactobacillus gasseri KML39 was selected based on its superior casein fermentation properties, proteolytic and antioxidant activities, and probiotic potential, including acid and bile tolerance and intestinal adhesion ability. We found that FSC significantly suppressed the expression of proinflammatory cytokines (COX-2, iNOS, TNF-α, IL-1β, and IL-6) and reduced nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells. In DSS-induced colitis mice, BW loss, shortened colon length, and colonic tissue damage were observed compared with the control group. Dextran sulfate sodium also activated NF-κB signaling, leading to the upregulation of iNOS and COX-2 in both colonic and brain tissues, along with elevated serum TNF-α and corticosterone levels. Furthermore, DSS treatment compromised intestinal and blood-brain barrier integrity, as indicated by the downregulation of tight junction proteins (occludin and claudin-5). Additionally, DSS negatively regulated neurotransmitter receptors (NMDAR, GABAR, and D2DR) and neurodevelopmental markers (BAX and Bcl-2) in the brain, suggesting neuroinflammatory and neurodegenerative effects. The FSC pretreatment effectively restored tight junction integrity, attenuated neuroinflammation, and improved gut microbiota composition. Notably, Proteobacteria and Bacteroides were significantly enriched in the DSS-treated group, whereas their abundance was normalized by FSC pretreatment. These findings highlight systemic inflammation as a key driver of colitis-associated neuroinflammation and demonstrate the potential of FSC as a therapeutic agent for gut-brain-microbiome axis dysfunction in colitis.