Czaja Albert J
Albert J Czaja, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, United States.
World J Gastroenterol. 2016 Nov 14;22(42):9257-9278. doi: 10.3748/wjg.v22.i42.9257.
The intestinal microbiome is a reservoir of microbial antigens and activated immune cells. The aims of this review were to describe the role of the intestinal microbiome in generating innate and adaptive immune responses, indicate how these responses contribute to the development of systemic immune-mediated diseases, and encourage investigations that improve the understanding and management of autoimmune hepatitis. Alterations in the composition of the intestinal microflora (dysbiosis) can disrupt intestinal and systemic immune tolerances for commensal bacteria. Toll-like receptors within the intestine can recognize microbe-associated molecular patterns and shape subsets of T helper lymphocytes that may cross-react with host antigens (molecular mimicry). Activated gut-derived lymphocytes can migrate to lymph nodes, and gut-derived microbial antigens can translocate to extra-intestinal sites. Inflammasomes can form within hepatocytes and hepatic stellate cells, and they can drive the pro-inflammatory, immune-mediated, and fibrotic responses. Diet, designer probiotics, vitamin supplements, re-colonization methods, antibiotics, drugs that decrease intestinal permeability, and molecular interventions that block signaling pathways may emerge as adjunctive regimens that complement conventional immunosuppressive management. In conclusion, investigations of the intestinal microbiome are warranted in autoimmune hepatitis and promise to clarify pathogenic mechanisms and suggest alternative management strategies.
肠道微生物群是微生物抗原和活化免疫细胞的储存库。本综述的目的是描述肠道微生物群在产生先天性和适应性免疫反应中的作用，指出这些反应如何促进全身性免疫介导疾病的发展，并鼓励开展相关研究以增进对自身免疫性肝炎的理解和管理。肠道微生物群组成的改变（生态失调）可破坏对共生细菌的肠道和全身免疫耐受。肠道内的Toll样受体可识别微生物相关分子模式，并塑造可能与宿主抗原发生交叉反应的辅助性T淋巴细胞亚群（分子模拟）。活化的肠道来源淋巴细胞可迁移至淋巴结，而肠道来源的微生物抗原可转移至肠外部位。炎性小体可在肝细胞和肝星状细胞内形成，并可驱动促炎、免疫介导和纤维化反应。饮食、设计益生菌（定制益生菌）、维生素补充剂、重新定植方法、抗生素、降低肠道通透性的药物以及阻断信号通路的分子干预措施可能会成为补充传统免疫抑制治疗的辅助方案。总之，自身免疫性肝炎有必要对肠道微生物群进行研究，有望阐明发病机制并提出替代管理策略。
