The Gut Microbiota: A Novel Player in Autoimmune Hepatitis.
The Gut Microbiota: A Novel Player in Autoimmune Hepatitis.
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DOI：
10.3389/fcimb.2022.947382
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发表时间：
2022
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
自身免疫性肝炎（AIH）是一种慢性免疫介导的肝脏疾病，全球各民族均有发病，且发病率呈上升趋势。若不加以治疗，该疾病会导致肝硬化、肝衰竭甚至死亡。肠道微生物群是存在于人体肠道内的一个复杂生态系统，广泛影响着人体的生理和病理过程。随着对肠道微生物群的认识愈发深入，大量研究已证实肠道微生物群在多种消化系统疾病中起着关键作用，包括酒精性肝病（ALD）和非酒精性脂肪性肝病（NAFLD）。然而，仅有少数研究关注评估AIH与肠道微生物群之间的关系。虽然AIH的发病机制尚未完全阐明，但一些研究表明，肠道微生物群可能通过触发若干特定信号通路、改变肠道微生物群代谢以及调节肠道和肝脏的免疫反应，对AIH的发生和发展起到重要作用。通过收集最新相关文献，本综述总结了AIH患者和AIH小鼠模型中需氧菌丰度的上升趋势。此外，研究发现AIH患者体内特定菌种的组合具有独特性，这有望成为诊断AIH的有效手段。另外，还存在管腔代谢物和免疫反应的改变，包括短链脂肪酸（SCFAs）减少、病原体相关分子模式（PAMPs）增加、调节性T（Treg）/辅助性T细胞17（Th17）失衡、滤泡调节性T（TFR）/滤泡辅助性T（TFH）细胞失衡以及自然杀伤性T（NKT）细胞活化。这些改变通过多种机制参与AIH的发病和进展。因此，一些基于恢复肠道微生物群组成的治疗方法，如益生菌和粪便微生物群移植（FMT），以及针对肠道微生物群相关信号通路的治疗方法，为AIH患者的治疗提供了新的思路。
Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease distributed globally in all ethnicities with increasing prevalence. If left untreated, the disease will lead to cirrhosis, liver failure, or death. The intestinal microbiota is a complex ecosystem located in the human intestine, which extensively affects the human physiological and pathological processes. With more and more in-depth understandings of intestinal microbiota, a substantial body of studies have verified that the intestinal microbiota plays a crucial role in a variety of digestive system diseases, including alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). However, only a few studies have paid attention to evaluate the relationship between AIH and the intestinal microbiota. While AIH pathogenesis is not fully elucidated yet, some studies have indicated that intestinal microbiota putatively made significant contributions to the occurrence and the development of AIH by triggering several specific signaling pathways, altering the metabolism of intestinal microbiota, as well as modulating the immune response in the intestine and liver. By collecting the latest related literatures, this review summarized the increasing trend of the aerobic bacteria abundance in both AIH patients and AIH mice models. Moreover, the combination of specific bacteria species was found distinct to AIH patients, which could be a promising tool for diagnosing AIH. In addition, there were alterations of luminal metabolites and immune responses, including decreased short-chain fatty acids (SCFAs), increased pathogen associated molecular patterns (PAMPs), imbalanced regulatory T (Treg)/Th17 cells, follicular regulatory T (TFR)/follicular helper T (TFH) cells, and activated natural killer T (NKT) cells. These alterations participate in the onset and the progression of AIH via multiple mechanisms. Therefore, some therapeutic methods based on restoration of intestinal microbiota composition, including probiotics and fecal microbiota transplantation (FMT), as well as targeted intestinal microbiota-associated signaling pathways, confer novel insights into the treatment for AIH patients.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
4
作者：
Hartmann P;Lang S;Zeng S;Duan Y;Zhang X;Wang Y;Bondareva M;Kruglov A;Fouts DE;Stärkel P;Schnabl B
通讯作者：
Schnabl B
影响因子：
4.5
作者：
Elsherbiny, Nahla M.;Rammadan, Mohammed;Hetta, Helal F.
通讯作者：
Hetta, Helal F.
影响因子：
2.1
作者：
Haider, A. S.;Kaye, G.;Thomson, A.
通讯作者：
Thomson, A.
影响因子：
5
作者：
Hsu, Mei-Chi;Liu, Sheng-Hung;Chiu, Peter J. S.
通讯作者：
Chiu, Peter J. S.