Shigemori Suguru, Shimosato Takeshi
Department of Bioscience and Food Production Science, Interdisciplinary Graduate School of Science and Technology, Shinshu University, Nagano, Japan; Japan Society for the Promotion of Science, Tokyo, Japan.
Department of Interdisciplinary Genome Sciences and Cell Metabolism, Institute for Biomedical Sciences, Shinshu University, Nagano, Japan; Supramolecular Complexes Unit, Research Center for Fungal and Microbial Dynamism, Shinshu University, Nagano, Japan.
Front Immunol. 2017 Jan 25;8:22. doi: 10.3389/fimmu.2017.00022. eCollection 2017.
Inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, are chronic inflammatory diseases characterized by dysregulated immune responses of the gastrointestinal tract. In recent years, the incidence of IBDs has increased in developed nations, but their prophylaxis/treatment is not yet established. Site-directed delivery of molecules showing anti-inflammatory properties using genetically modified (gm)-probiotics shows promise as a new strategy for the prevention and treatment of IBD. Advantages of gm-probiotics include (1) the ability to use bacteria as a delivery vehicle, enabling safe and long-term use by humans, (2) decreased risks of side effects, and (3) reduced costs. The intestinal delivery of anti-inflammatory proteins such as cytokines and enzymes using has been shown to regulate host intestinal homeostasis depending on the delivered protein-specific machinery. Additionally, clinical experience using interleukin 10-secreting has been shown to be safe and to facilitate biological containment in IBD therapy. On the other hand, some preclinical studies have demonstrated that gm-strains of immunobiotics (probiotic strains able to beneficially regulate the mucosal immunity) provide beneficial effects on intestinal inflammation as a result of the synergy between the immunoregulatory effects of the bacterium itself and the anti-inflammatory effects of the delivered recombinant proteins. In this review, we discuss the rapid progression in the development of strategies for the prophylaxis and treatment of IBD using gm-probiotics that exhibit immune regulation effects (gm-immunobiotics). In particular, we discuss the type of strains used as delivery agents.
炎症性肠病（IBDs），包括溃疡性结肠炎和克罗恩病，是一类慢性炎症性疾病，其特征为胃肠道免疫反应失调。近年来，IBDs在发达国家的发病率有所上升，但其预防/治疗方法尚未确立。利用基因改造（gm）益生菌定点递送具有抗炎特性的分子，有望成为预防和治疗IBD的新策略。gm益生菌的优势包括：（1）能够将细菌用作递送载体，使人类能够安全长期使用；（2）副作用风险降低；（3）成本降低。使用[具体方式]进行细胞因子和酶等抗炎蛋白的肠道递送，已被证明可根据所递送蛋白的特异性机制调节宿主肠道内稳态。此外，使用分泌白细胞介素10的[具体菌株]的临床经验表明，其在IBD治疗中是安全的，且有助于生物控制。另一方面，一些临床前研究表明，免疫益生菌（能够有益地调节黏膜免疫的益生菌菌株）的gm菌株，由于细菌自身的免疫调节作用与所递送重组蛋白的抗炎作用之间的协同作用，对肠道炎症具有有益影响。在本综述中，我们讨论了使用具有免疫调节作用的gm益生菌（gm免疫益生菌）预防和治疗IBD策略的快速发展。特别是，我们讨论了用作递送剂的菌株类型。
