Investigating the modulatory effects of probiotics, paraprobiotics, and whey protein on DSS-induced colitis in mice

學生姓名: 劉詠潔
指導教授: 黃崇雄
學期: 114下
摘  要: Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease, and its clinical management is often limited by drug-related adverse effects, inconsistent therapeutic efficacy, and the challenges associated with long-term use. Although probiotics have been considered to possess potential for ameliorating intestinal inflammation, their application remains constrained by poor intestinal colonization,
susceptibility to antibiotics and environmental factors, and safety concerns in specific populations. This integrative study aimed to compare the therapeutic efficacy of probiotics and their corresponding paraprobiotics derived from different strains, including L. plantarum, L. sakei, and L. reuteri, in the treatment of UC, and to further investigate the effects of whey protein, either alone or in combination with L.
rhamnosus GG, on intestinal inflammation and metabolomic regulation. In these studies, C57BL/6J mice were used as the experimental animals, and colitis was induced by administration of 3% dextran sulfate sodium (DSS) in the drinking water. The animals received different probiotic strains, paraprobiotics, or whey protein combined with probiotics depending on the respective study design. Evaluated parameters included clinical manifestations, such as body weight change and disease activity index (DAI), histological scoring, immune responses, myeloperoxidase (MPO) activity, inflammatory cytokines (TNF-α and IL-6), expression of intestinal barrier-related genes (zonula occludens-1, Occludin, and Mucin-1), and plasma metabolomic analysis using nuclear magnetic resonance (NMR). The results showed that, in both in vitro and in vivo experiments, paraprobiotics derived from L. plantarum MGEL20154 and L. reuteri MGEL21001 were superior to live probiotics in antioxidant activity, anti-inflammatory effects, and intestinal tight junction repair. Paraprobiotics significantly upregulated Zo4 1 and Muc-1 expression in colonic tissue, while also overcoming the limitations of live probiotics associated with poor stability under gastric acid and high-temperature conditions. In addition, whey protein administered alone or in combination with probiotics effectively attenuated body weight loss and improved DAI scores. Histological analysis further showed that the whey protein-plus-probiotics treatment group exhibited significantly reduced inflammatory cell infiltration. Overall, these findings indicate that both paraprobiotics and whey protein combined with probiotics have potential as non-pharmacological intervention strategies for UC. They also provide important evidence supporting the development of microbiome drugs and functional foods, particularly in addressing the limitations of live probiotics in terms of storage stability and safety