Alleviating Effect of Lactiplantibacillus plantarum HYY-S10 on Colitis in Mice Based on an Analysis of the Immune Axis in the Intestine

The pathogenesis of ulcerative colitis (UC) has been fundamentally associated with intestinal microbiota dysbiosis and disruption of immune homeostasis. This study systematically investigates the therapeutic potential of <i>Lactiplantibacillus plantarum</i> HYY-S10 (HYY-S10), a novel strain isolated from De'ang sour tea in Yun an, China, with a focus on its mechanisms for alleviating colitis through the modulation of gut microbiota. Using a dextran sulfate sodium (DSS)-induced colitis model in C57BL/6J mice, our findings demonstrated that seven days of oral supplementation with HYY-S10 (1 × 10⁸ CFU/mL, 0.2 mL/10 g body weight) significantly improved Disease Activity Index (DAI) scores and attenuated characteristic colitis symptoms, including progressive weight loss, rectal bleeding, and abnormal stool consistency. Administration of HYY-S10 exhibited significant immunomodulatory effects characterized by the downregulation of pro-inflammatory mediators (such as IL-1β, IL-6, IFN-γ, and LPS) while concomitantly upregulating anti-inflammatory IL-10 expression. Additionally, the strain enhanced intestinal antioxidant capacity by increasing GSH-Px activity, which collectively contributed to the reduction in intestinal inflammation. Furthermore, HYY-S10 demonstrated multifaceted protective effects by ameliorating oxidative stress through the restoration of redox homeostasis and modulation of gut microbial ecology. Probiotic intervention significantly increased short-chain fatty acids (SCFAs) production and notably enhanced the relative abundance of beneficial taxa, including <i>Akkermansia</i> and <i>Ruminococcus</i>_B, while restoring microbial diversity and ecological stability. Collectively, our results demonstrate that HYY-S10 alleviates experimental colitis by modulating the intestinal immune axis and microbiota composition, providing mechanistic insights to support its potential as a probiotic-based therapeutic strategy for UC.