Table 1_Probiotics and the intestinal tight junction barrier function.docx

Disruption of the intestinal epithelial tight junction (TJ) barrier is a key pathogenic factor in numerous gastrointestinal (GI) disorders, including inflammatory bowel disease, irritable bowel syndrome, necrotizing enterocolitis, and enteric infections. The gut microbiota plays a pivotal role in regulating epithelial integrity, and emerging evidence highlights the therapeutic potential of probiotics in preserving or restoring TJ barrier function. This review summarizes the current literature on the protective effects of probiotics in modulating intestinal epithelial TJ barrier function. Specific strains of Lactobacillus, Bifidobacterium, Escherichia coli Nissle 1917, Bacillus subtilis, and Saccharomyces boulardii have been shown to enhance barrier integrity in cell culture, animal models, and in some clinical settings. These probiotics exert their effects through diverse mechanisms, including the upregulation of TJ proteins (e.g., occludin, claudins, ZO-1), suppression of proinflammatory cytokines, inhibition of NF-κB, myosin light chain kinase (MLCK) and MAPK signaling pathways, and activation of host pattern recognition receptors such as TLR-2 and PPARγ. Moreover, several studies highlight the strain-specific nature of these effects, underscoring the importance of identifying and characterizing individual probiotic strains for therapeutic use. Taken together, the data reviewed here support the potential of probiotics as adjunctive or preventive therapies targeting epithelial barrier dysfunction in a range of GI diseases. However, further mechanistic studies, clinical trials, and standardization of probiotic formulations are needed to translate these findings into effective, personalized interventions. This review highlights both the promise and complexity of probiotic-mediated intestinal barrier regulation and provides new insight for future research in this rapidly evolving field.

肠道上皮紧密连接（tight junction, TJ）屏障破坏是多种胃肠道（gastrointestinal, GI）疾病的关键致病因素，涵盖炎症性肠病、肠易激综合征、坏死性小肠结肠炎及肠道感染。肠道菌群在调控上皮完整性方面发挥核心作用，越来越多的研究证据表明，益生菌在维持或恢复TJ屏障功能上具备治疗潜力。本综述总结了当前关于益生菌调控肠道上皮TJ屏障功能的保护作用的相关文献。特定菌株的乳杆菌属（Lactobacillus）、双歧杆菌属（Bifidobacterium）、大肠杆菌Nissle 1917（Escherichia coli Nissle 1917）、枯草芽孢杆菌（Bacillus subtilis）及布拉迪酵母菌（Saccharomyces boulardii）已被证实可在细胞培养、动物模型与部分临床场景中增强屏障完整性。这些益生菌通过多种途径发挥作用：上调紧密连接蛋白（如闭合蛋白occludin、紧密连接蛋白claudins、闭锁小带蛋白1 ZO-1）、抑制促炎细胞因子、阻断核因子κB（NF-κB）、肌球蛋白轻链激酶（myosin light chain kinase, MLCK）与丝裂原活化蛋白激酶（MAPK）信号通路，以及激活宿主模式识别受体如Toll样受体2（TLR-2）与过氧化物酶体增殖物激活受体γ（PPARγ）。此外，多项研究强调了这些效应的菌株特异性，凸显了筛选并鉴定可用于治疗的单个益生菌菌株的重要性。综合来看，本综述涵盖的研究数据支持益生菌作为辅助或预防性疗法的潜力，可靶向改善多种胃肠道疾病中的上皮屏障功能障碍。然而，仍需开展更多机制研究、临床试验及益生菌制剂的标准化工作，才能将这些研究发现转化为有效的个性化干预手段。本综述既阐明了益生菌介导的肠道屏障调控的前景与复杂性，也为这一快速发展领域的未来研究提供了全新视角。