Pediococcus acidilactici ZQ-19 Ameliorates Ulcerative Colitis via Remodeling Gut Microbiota and Glutathione Redox Homeostasis.

Ulcerative colitis (UC) is closely linked to intestinal oxidative stress, gut dysbiosis and selenium metabolism disorders. In this study, 449 lactic acid bacteria strains were isolated from yak yogurt on the Qinghai-Tibet Plateau. After H2O2 tolerance screening, 11 highly antioxidant strains were obtained, among which Pediococcus acidilactici ZQ-19 exhibited the highest intracellular GPx activity, outstanding free radical scavenging capacity and excellent probiotic characteristics. In DSS-induced UC mice, ZQ-19 significantly alleviated weight loss, colon shortening and mucosal damage, restored tight junction protein expression, and protected liver and kidney functions. 16 S rRNA sequencing revealed that ZQ-19 was associated with reshaped gut microbiota, enriched butyrate-producing taxa and reduced pro-inflammatory pathogens; such microbial shifts were positively correlated with elevated intestinal GPx activity. Mechanistically, ZQ-19 intervention coincided with enhanced intestinal ROS clearance, altered expression of GR/GST/Trx-1, and a shifted selenoprotein profile favouring GPx isoforms by upregulating colonic SELENOP and GPx1-4 while downregulating DIO1/2. It synergistically activated Nrf2/p53 protective pathways and inhibited the MyD88/COX-2/NOX1/2 pro-oxidative inflammatory axis, with superior local regulation to mesalazine. In conclusion, ZQ-19 ameliorates UC in association with the microbiota-GPx axis and dual pathways, offering a novel probiotic intervention strategy.