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.

宿主与微生物的相互作用是免疫系统发展的基础。现代环境和生活方式的急剧变化导致了这种进化古老过程的失衡，恰逢免疫介导的疾病（例如自身免疫性疾病，过敏性疾病和慢性炎症性疾病）急剧上升。迫切需要在粘膜和皮肤微生物群的背景下更好地了解这些疾病。这篇综述讨论了在有遗传倾向的宿主中微生物群如何促进免疫介导疾病的易感性，引发和永存的机制。由于最近在该领域做出了许多新的研究，所以这是及时的，从人类的宏基因组学研究，致敏模型和体外系统中宿主与微生物相互作用的机理研究，到在免疫介导的疾病中具有更广泛影响的分子机制。我们专注于一般原则，例如违反免疫耐受性和屏障，导致肠道，口腔和皮肤微生物群促进免疫介导的疾病。最后，将探索靶向微生物群，屏障表面或宿主免疫系统以恢复耐受性和体内平衡的治疗途径。