Lacticaseibacillus paracasei JY062 Postbiotic Alleviated 3% DSS-Induced Colitis in Mice via Integrated Antioxidant, Barrier Repair, Immunomodulatory and Microbiota Modulation

Ulcerative colitis (UC) with multifactorial etiology remains clinically challenging. While current pharmacotherapies alleviate symptoms, their long-term application is constrained by significant side effects. Lacticaseibacillus paracasei JY062 postbiotic (Pa JY062) exerts multi-target therapeutic effects via integrated antioxidant, barrier repair, immunomodulatory and microbiota modulation for UC. Pa JY062 exhibited potent antioxidant capacity and reduced reactive oxygen species (ROS) in Caco-2 cells. In DSS-colitis mice, high-dose Pa JY062 (HP, 800 mg/kg) restored intestinal barrier integrity (Evans blue permeability: 0.0547 vs. 0.107, p < 0.01), enhanced antioxidant defenses (SOD: 9.43 vs. 5.5; GSH-Px: 62.74 vs. 40.94 U/mg protein, p < 0.01), and rebalanced Th1/Th2/Th17/Treg responses. LigiLactobacillus murinus (L. murinus) was enriched, while Bacteroides acidifaciens (B. acidifaciens) was diminished, SCFAs increased (acetate 2772.70 ± 21.08, propionate 669.84 ± 6.79, butyrate 324.14 ± 0.42 μg/g). Spearman correlations linked L. murinus to barrier proteins (ZO-1/Occludin/E-cadherin), contrasting B. acidifaciens–inflammation associations. These findings revealed that Pa JY062 exerted multi-target therapeutic effects on UC, and offered a wider array of options for intestinal health. Pa JY062 represents a promising natural antioxidant-based strategy for UC management.