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自身免疫性肝炎患者的肠道微生物组和通透性。

Intestinal microbiome and permeability in patients with autoimmune hepatitis.

机构信息

Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300052, PR China.

Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300052, PR China.

出版信息

Best Pract Res Clin Gastroenterol. 2017 Dec;31(6):669-673. doi: 10.1016/j.bpg.2017.09.013. Epub 2017 Sep 18.

Abstract

Autoimmune hepatitis (AIH) is a severe inflammatory liver disease. The underlying mechanisms remain unclear, but recent studies provided new perspectives on altered intestinal microbiome and permeability in AIH animal models and patients, highlighting gut-liver crosstalk in the pathogenesis of AIH. Transgenic AIH mice carrying HLA-DR3 showed reduced diversity and total load of gut microbiota. Germ-free mice are resistant to concanavalin A-induced liver injury, whereas enterogenouss antigens induce the activation of natural killer T cells participating in concanavalin A-induced liver injury, supporting the close relationship between microbiota and AIH. Moreover, 'molecular mimicry' provides a plausible interpretation of the immune reactions between microorganic antigens and liver autoantigens, for instance, cytochrome P4502D6, the target of cross-reactivity between virus and self. Nevertheless, direct evidence for the intestinal microbiome and permeability in AIH is still limited. The relationship between AIH susceptibilities and an intestinal microbiome shaped by drugs, diets or genes needs further study.

摘要

自身免疫性肝炎(AIH)是一种严重的炎症性肝病。其潜在机制尚不清楚,但最近的研究为 AIH 动物模型和患者中肠道微生物组和通透性的改变提供了新的视角,强调了肠道-肝脏相互作用在 AIH 发病机制中的作用。携带 HLA-DR3 的转基因 AIH 小鼠显示出肠道微生物群多样性和总负荷减少。无菌小鼠对刀豆蛋白 A 诱导的肝损伤具有抗性,而肠源性抗原诱导参与刀豆蛋白 A 诱导的肝损伤的自然杀伤 T 细胞的激活,支持微生物群与 AIH 之间的密切关系。此外,“分子模拟”为微生物抗原和肝自身抗原之间的免疫反应提供了一个合理的解释,例如细胞色素 P4502D6,是病毒和自身之间交叉反应的靶标。然而,AIH 中肠道微生物组和通透性的直接证据仍然有限。药物、饮食或基因塑造的肠道微生物组与 AIH 易感性之间的关系需要进一步研究。

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