The mammalian intestine is colonized by trillions of microorganisms that are collectively referred to as the gut microbiota. The majority of symbionts have co-evolved with their host in a mutualistic relationship that benefits both. Under certain conditions, such as in Crohn’s disease, a subtype of inflammatory bowel disease, some symbionts bloom to cause disease in genetically susceptible hosts. Although the identity and function of disease-causing microorganisms or pathobionts in Crohn’s disease remain largely unknown, mounting evidence from animal models suggests that pathobionts triggering Crohn’s disease-like colitis inhabit certain niches and penetrate the intestinal tissue to trigger inflammation. In this Review, we discuss the distinct niches occupied by intestinal symbionts and the evidence that pathobionts triggering Crohn’s disease live in the mucus layer or near the intestinal epithelium. We also discuss how Crohn’s disease-associated mutations in the host disrupt intestinal homeostasis by promoting the penetration and accumulation of pathobionts in the intestinal tissue. Finally, we discuss the potential role of microbiome-based interventions in precision therapeutic strategies for the treatment of Crohn’s disease.

哺乳动物肠道被数万亿微生物定植，这些微生物统称为肠道微生物群。大多数共生体都是在对双方都有利的互惠关系中与宿主共同进化的。在某些情况下，例如克罗恩病（炎性肠病的一种亚型）中，一些共生体会大量繁殖，在遗传易感宿主中引起疾病。尽管克罗恩病中致病微生物或致病微生物的身份和功能在很大程度上仍不清楚，但来自动物模型的越来越多的证据表明，引发克罗恩病样结肠炎的致病微生物栖息在某些生态位并穿透肠道组织引发炎症。在这篇综述中，我们讨论了肠道共生体占据的不同生态位，以及触发克罗恩病的致病菌存在于粘液层或肠上皮附近的证据。我们还讨论了宿主中与克罗恩病相关的突变如何通过促进致病菌在肠道组织中的渗透和积累来破坏肠道稳态。最后，我们讨论了基于微生物组的干预措施在治疗克罗恩病的精准治疗策略中的潜在作用。