Background/Objectives: Lactiplantibacillus plantarum DSW3805 was isolated from Korean kimchi samples to examine its effect in a dextran sulfate sodium (DSS)-induced mouse model. Methods: To induce colitis, mice were treated with DSS for one week before sacrifice (n = 8 per group, total n = 40). Lacticaseibacillus rhamnosus GG (109 CFU/day) or probiotics (L. plantarum DSW3805; 108 or 109 CFU/day) were administered for two weeks. To assess colitis damage, we evaluated the disease activity index, colon tissue, inflammatory factors, the microbiome, short-chain fatty acids, and intestine-related factors. Results: DSS induced colonic tissue damage (colon length, mucus thickness, and colonic crypts), and L. plantarum DSW3805 alleviated the tissue damage. Induced inflammation was reduced by inhibiting TNF-α, IFN-γ, IL-1β, IL-6, IgA, IgG, LTB4, PGE2, and NF-κB protein expression. The ratio of Firmicutes to Bacteroidetes in the PC group (DSS-treated control) was lower than that in the NC (DSS-nontreated control); L. plantarum DSW3805 increased the ratio. Higher concentrations of acetic, propionic, and butyric acids were detected in probiotic groups. In addition, harmful factors, such as calprotectin and β-glucuronidase, were reduced in the probiotic groups. Conclusions: L. plantarum DSW3805 alleviates gut damage by colitis; therefore, it can be used as a functional food to improve gut health.
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