大肠杆菌Nissle 1917对炎症性肠病治疗作用的研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2022-1027

摘要/Abstract

摘要：

炎症性肠病（inflammatory bowel disease，IBD）是一组特定的肠道疾病的统称，主要体现为慢性及复发性的肠道炎症。其全球发病率正在迅速上升，严重影响人们生活质量与生命健康，已成为当前的全球性健康问题。在过去的几十年里，大量研究表明IBD的发病率与肠道菌群失调有关。因此，以肠道益生菌为主的治疗策略成为一大热点，其中大肠杆菌Nissle 1917（Escherichia coli Nissle 1917，EcN）备受关注。本文聚焦肠道益生菌EcN在治疗IBD中的应用与机制，系统地综述了EcN的益生菌特性，概述EcN在临床实践中对IBD的治疗应用，同时从上皮屏障完整性调节、免疫调节、黏液屏障保护和肠道菌群稳态等方面阐述EcN治疗IBD的具体作用机制。此外，结合当前的研究现状，讨论了未来基于工程化EcN新疗法的发展前景，强调EcN在IBD治疗和预防中的适用性和可行性策略，并对该领域未来的研究方向进行了展望，为进一步深入研究EcN治疗IBD提供思路和参考。

关键词: 炎症性肠病, 大肠杆菌Nissle 1917, 治疗作用

Abstract:

Inflammatory bowel disease（IBD）is a general term of a group of specific intestinal diseases, mainly manifested as chronic and recurrent intestinal inflammation. The burden of IBD has been a global health concern since its incidence and prevalence are elevating rapidly, which has seriously affected people's life and health quality. Over the past decades, tremendous studies underlined the association between incidence of IBD with imbalance of intestinal flora. Therefore, the treatment strategy based on probiotics has become the focus, among of them Escherichia coli Nissle 1917（EcN）has received accumulative attentions. In the current work, we focused on the application and mechanisms of EcN in the treatment of IBD, systematically reviewed the probiotic properties of EcN and its application for treating IBD through regulating epithelial integrity, immune-modulation, mucus protection and gut microbiota homeostasis. Furthermore, the future perspectives on formulating novel therapies based on engineered EcN were discussed, highlighting the applicable and feasible strategies of EcN in IBD curing and prevention. Besides, the prospects for further research in this field were given, providing ideas and references for further in-depth research on the EcN treatment of IBD.

Key words: inflammatory bowel disease, Escherichia coli Nissle 1917, therapeutic effect

陈彩萍, 任昊, 龙腾飞, 何冰, 鲁兆祥, 孙坚. 大肠杆菌Nissle 1917对炎症性肠病治疗作用的研究进展[J]. 生物技术通报, 2023, 39(6): 109-118.

CHEN Cai-ping, REN Hao, LONG Teng-fei, HE Bing, LU Zhao-xiang, SUN Jian. Research Advances in the Treatment of Inflammation Bowel Disease Using Escherichia coli Nissle 1917[J]. Biotechnology Bulletin, 2023, 39(6): 109-118.

图/表 2

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动物模型 Model	研究目的 Aim	诱导物 Stimuli	持续时间 Duration/d	疗效 Therapeutic fffect	总结 Conclusion	参考文献 Reference
大鼠结肠炎模型	比较不同疗程、不同剂量的EcN对大鼠结肠炎的治疗作用	TNBS	15	低剂量EcN可治疗大鼠结肠炎，但长期服用大剂量EcN可能加重大鼠结肠炎的症状	EcN与不同抗生素联合使用时，具有协同治疗效果，但EcN可能存在产生抗生素耐药性的风险；单独口服一定量EcN具有治疗结肠炎的作用，但从多个试验结果表明，EcN能通过其他方式提高其治疗结肠炎的效果	[23]
大鼠结肠炎模型	比较利福昔明和EcN对大鼠结肠炎的治疗作用	乙酸溶液	8	利福昔明与EcN联合应用具有协同抗炎作用		[24]
小鼠结肠炎模型	探究EcN和米诺环素在小鼠复发性结肠炎中的关联	DSS	31	在米诺环素治疗过程中补充EcN可降低小鼠肠道炎症的损伤程度，防止实验性结肠炎的复发		[25]
小鼠结肠炎模型	评估预防性摄入EcN在小鼠结肠炎中的作用	DSS	28	小鼠预防性摄入EcN能改善结肠炎症状		[26]

动物模型 Model	研究目的 Aim	诱导物 Stimuli	持续时间 Duration/d	疗效 Therapeutic fffect	总结 Conclusion	参考文献 Reference
大鼠结肠炎模型	比较不同疗程、不同剂量的EcN对大鼠结肠炎的治疗作用	TNBS	15	低剂量EcN可治疗大鼠结肠炎，但长期服用大剂量EcN可能加重大鼠结肠炎的症状	EcN与不同抗生素联合使用时，具有协同治疗效果，但EcN可能存在产生抗生素耐药性的风险；单独口服一定量EcN具有治疗结肠炎的作用，但从多个试验结果表明，EcN能通过其他方式提高其治疗结肠炎的效果	[23]
大鼠结肠炎模型	比较利福昔明和EcN对大鼠结肠炎的治疗作用	乙酸溶液	8	利福昔明与EcN联合应用具有协同抗炎作用		[24]
小鼠结肠炎模型	探究EcN和米诺环素在小鼠复发性结肠炎中的关联	DSS	31	在米诺环素治疗过程中补充EcN可降低小鼠肠道炎症的损伤程度，防止实验性结肠炎的复发		[25]
小鼠结肠炎模型	评估预防性摄入EcN在小鼠结肠炎中的作用	DSS	28	小鼠预防性摄入EcN能改善结肠炎症状		[26]