Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
Department of Neurology, Yale School of Medicine, New Haven, CT, USA.
Nat Rev Microbiol. 2020 Sep;18(9):521-538. doi: 10.1038/s41579-020-0367-2. Epub 2020 May 26.
Host-microbiota interactions are fundamental for the development of the immune system. Drastic changes in modern environments and lifestyles have led to an imbalance of this evolutionarily ancient process, coinciding with a steep rise in immune-mediated diseases such as autoimmune, allergic and chronic inflammatory disorders. There is an urgent need to better understand these diseases in the context of mucosal and skin microbiota. This Review discusses the mechanisms of how the microbiota contributes to the predisposition, initiation and perpetuation of immune-mediated diseases in the context of a genetically prone host. It is timely owing to the wealth of new studies that recently contributed to this field, ranging from metagenomic studies in humans and mechanistic studies of host-microorganism interactions in gnotobiotic models and in vitro systems, to molecular mechanisms with broader implications across immune-mediated diseases. We focus on the general principles, such as breaches in immune tolerance and barriers, leading to the promotion of immune-mediated diseases by gut, oral and skin microbiota. Lastly, the therapeutic avenues that either target the microbiota, the barrier surfaces or the host immune system to restore tolerance and homeostasis will be explored.
宿主-微生物群相互作用是免疫系统发育的基础。现代环境和生活方式的剧烈变化导致了这一进化古老过程的失衡，同时免疫介导的疾病（如自身免疫、过敏和慢性炎症性疾病）也急剧增加。迫切需要在黏膜和皮肤微生物群的背景下更好地理解这些疾病。
这篇综述讨论了在遗传易感性宿主的背景下，微生物组如何有助于免疫介导疾病的易感性、起始和持续存在的机制。由于最近在该领域的大量新研究，包括人类的宏基因组研究以及无菌模型和体外系统中宿主-微生物相互作用的机制研究，以及在免疫介导疾病中具有更广泛意义的分子机制研究，该综述具有及时性。
我们重点讨论了一般原则，例如免疫耐受和屏障的破坏，导致肠道、口腔和皮肤微生物群促进免疫介导的疾病。最后，将探讨靶向微生物组、屏障表面或宿主免疫系统以恢复耐受和动态平衡的治疗途径。
