Okumura Ryu, Takeda Kiyoshi
1Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka, 565-0871 Japan.
2WPI Immunology Frontier Research Center, Osaka University, Osaka, 565-0871 Japan.
Inflamm Regen. 2018 Apr 2;38:5. doi: 10.1186/s41232-018-0063-z. eCollection 2018.
The intestine is inhabited by a tremendous number of microorganisms, which provide many benefits to nutrition, metabolism and immunity. Mucosal barriers by intestinal epithelial cells make it possible to maintain the symbiotic relationship between the gut microbiota and the host by separating them. Recent evidence indicates that mucosal barrier dysfunction contributes to the development of inflammatory bowel disease (IBD). In this review, we focus on the mechanisms by which mucosal barriers maintain gut homeostasis.
Gut mucosal barriers are classified into chemical and physical barriers. Chemical barriers, including antimicrobial peptides (AMPs), are chemical agents that attack invading microorganisms, and physical barriers, including the mucus layer and the cell junction, are walls that physically repel invading microorganisms. These barriers, which are ingeniously modulated by gut microbiota and host immune cells, spatially segregate gut microbiota and the host immunity to avoid unnecessary immune responses to gut commensal microbes. Therefore, mucosal barrier dysfunction allows gut bacteria to invade gut mucosa, inducing excessive immune responses of the host immune cells, which result in intestinal inflammation.
Gut mucosal barriers constructed by intestinal epithelial cells maintain gut homeostasis by segregating gut microbiota and host immune cells. Impaired mucosal barrier function contributes to the development of IBD. However, the mechanism by which the mucosal barrier is regulated by gut microbiota remains unclear. Thus, it should be further elucidated in the future to develop a novel therapeutic approach to IBD by targeting the mucosal barrier.
肠道中栖息着大量微生物,它们在营养、代谢和免疫方面带来诸多益处。肠道上皮细胞形成的黏膜屏障通过将肠道微生物群与宿主分隔开,从而维持它们之间的共生关系。近期证据表明,黏膜屏障功能障碍会促使炎症性肠病(IBD)的发展。在本综述中,我们聚焦于黏膜屏障维持肠道稳态的机制。
肠道黏膜屏障分为化学屏障和物理屏障。化学屏障包括抗菌肽(AMPs),是攻击入侵微生物的化学物质;物理屏障包括黏液层和细胞连接,是物理性排斥入侵微生物的屏障。这些屏障受到肠道微生物群和宿主免疫细胞的巧妙调节,在空间上分隔肠道微生物群和宿主免疫,以避免对肠道共生微生物产生不必要的免疫反应。因此,黏膜屏障功能障碍会使肠道细菌侵入肠道黏膜,引发宿主免疫细胞的过度免疫反应,进而导致肠道炎症。
肠道上皮细胞构建的肠道黏膜屏障通过分隔肠道微生物群和宿主免疫细胞来维持肠道稳态。黏膜屏障功能受损会促使IBD的发展。然而,肠道微生物群调节黏膜屏障的机制仍不清楚。因此,未来应进一步阐明,以便通过靶向黏膜屏障开发IBD的新型治疗方法。