Caruso Roberta, Lo Bernard C, Chen Grace Y, Núñez Gabriel
Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
Department of Internal Medicine and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
Nat Rev Gastroenterol Hepatol. 2024 Oct 24. doi: 10.1038/s41575-024-00997-y.
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.
哺乳动物的肠道中栖息着数万亿微生物，它们统称为肠道微生物群。大多数共生体与宿主共同进化，形成互利共生关系，对双方都有益。在某些情况下，如在炎症性肠病的一种亚型克罗恩病中，一些共生体大量繁殖，在基因易感性宿主中引发疾病。尽管克罗恩病中致病微生物或致病共生体的身份和功能在很大程度上仍不清楚，但动物模型的证据越来越多，表明引发克罗恩病样结肠炎的致病共生体栖息在某些生态位，并穿透肠道组织引发炎症。在本综述中，我们讨论了肠道共生体占据的不同生态位，以及引发克罗恩病的致病共生体存在于黏液层或肠道上皮附近的证据。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共生体在肠道组织中的穿透和积累来破坏肠道稳态。最后，我们讨论了基于微生物群的干预措施在克罗恩病精准治疗策略中的潜在作用。
