Lactobacillus paracasei WIS43 alleviates DSS-induced colitis by modulating gut microbiota and suppressing inflammation

Introduction Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon with rising incidence and limited therapeutic options. Probiotics are increasingly recognized as potential interventions, but strain-specific differences remain insufficiently defined. Methods We conducted a meta-analysis of publicly available microbiome datasets to characterize disease-associated dysbiosis, focusing on the genus Lactobacillus . We then evaluated Lactobacillus paracasei WIS43, a novel strain isolated from the breast milk of a healthy volunteer, in a dextran sulfate sodium (DSS)-induced murine colitis model, using mesalazine and the commercial strain Lactobacillus paracasei LPC-37 as comparators. Disease severity, histopathology, inflammatory cytokines, and gut microbiota composition were systematically assessed. Results Meta-analysis confirmed a significant depletion of Lactobacillus in UC patients. In vivo , WIS43 treatment reduced body weight loss, disease activity index scores, and colon shortening. Histological analysis revealed preserved epithelial integrity and reduced inflammatory infiltration. WIS43 significantly decreased serum and colonic TNF- α , IL-6, and IL-1β levels, demonstrating stronger anti-inflammatory activity than LPC-37 and comparable efficacy to mesalazine. 16S rRNA sequencing further showed that WIS43 restored beneficial taxa, including Lactobacillus johnsonii and Lactobacillus taiwanensis , while reducing potentially pathogenic bacteria. Conclusion These findings identify WIS43 as a promising probiotic candidate for the prevention and treatment of UC, supporting its therapeutic potential through coordinated modulation of host immunity and gut microbiota.