Vindigni Stephen M, Zisman Timothy L, Suskind David L, Damman Christopher J
Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA, USA.
Department of Pediatrics, Seattle Children's Hospital and University of Washington, Seattle, WA, USA.
Therap Adv Gastroenterol. 2016 Jul;9(4):606-25. doi: 10.1177/1756283X16644242. Epub 2016 Apr 19.
We discuss the tripartite pathophysiological circuit of inflammatory bowel disease (IBD), involving the intestinal microbiota, barrier function, and immune system. Dysfunction in each of these physiological components (dysbiosis, leaky gut, and inflammation) contributes in a mutually interdependent manner to IBD onset and exacerbation. Genetic and environmental risk factors lead to disruption of gut homeostasis: genetic risks predominantly affect the immune system, environmental risks predominantly affect the microbiota, and both affect barrier function. Multiple genetic and environmental 'hits' are likely necessary to establish and exacerbate disease. Most conventional IBD therapies currently target only one component of the pathophysiological circuit, inflammation; however, many patients with IBD do not respond to immune-modulating therapies. Hope lies in new classes of therapies that target the microbiota and barrier function.
我们讨论了炎症性肠病（IBD）的三方病理生理回路，涉及肠道微生物群、屏障功能和免疫系统。这些生理成分中的每一个功能失调（生态失调、肠漏和炎症）都以相互依存的方式促成IBD的发病和加重。遗传和环境风险因素导致肠道稳态的破坏：遗传风险主要影响免疫系统，环境风险主要影响微生物群，两者都影响屏障功能。建立和加重疾病可能需要多个遗传和环境“打击”。目前大多数传统的IBD疗法仅针对病理生理回路的一个成分，即炎症；然而，许多IBD患者对免疫调节疗法没有反应。希望在于针对微生物群和屏障功能的新型疗法。
