Probiotic Lactiplantibacillus plantarum strains attenuate Salmonella-induced inflammation through coordinated cytokine and redox regulation.

The intestinal epithelium is a major target of oxidative and inflammatory injury during Salmonella infection, and probiotics with coordinated immunomodulatory and antioxidant activities represent promising candidates for host protection. In this study, bacteria Lactiplantibacillus plantarum strains MKNK15, MKNK17Y, MKNK25 and MKNK28 isolated from the traditional fermented foods of northeast India were evaluated for their tolerance to gastrointestinal stress, epithelial adhesion capacity and their ability to modulate Salmonella-induced cellular dysfunction. All strains displayed strong survival under acidic, bile, pancreatin and pepsin conditions, with MKNK25 and MKNK28 exhibiting the highest acid and pepsin tolerance. The strains adhered effectively to Caco-2 monolayers and significantly attenuated Salmonella-mediated cytotoxicity by reducing apoptosis and necrosis while increasing cell viability. Mechanistically, probiotic pretreatment markedly suppressed Salmonella-induced accumulation of nitric oxide (NO) and restored intracellular redox balance by elevating glutathione (GSH) and superoxide dismutase (SOD) activity in RAW 264.7 macrophages. These antioxidant effects were accompanied by recovery of ATP levels, indicating protection from metabolic collapse during infection. In epithelial cells, the strains preserved barrier integrity, as demonstrated by significantly higher transepithelial electrical resistance (TEER) compared with infected controls. Whole-genome sequencing revealed strain-dependent variation in coding sequences, GC content and gene functions associated with metabolic adaptability and stress tolerance, supporting their physiological performance. Together, these findings identify MKNK15, MKNK17Y, MKNK25 and MKNK28 as promising immunobiotic candidates that protect epithelial and immune cells from Salmonella-induced oxidative–inflammatory injury through combined antioxidant, anti-inflammatory and cytoprotective mechanisms.