Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease
Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease
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DOI：
10.1136/gutjnl-2015-310585
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发表时间：
2016-05-01
期刊：
影响因子：
24.5
通讯作者：
Perlemuter, G.
中科院分区：
文献类型：
--
作者：
Llopis, M.;Cassard, A. M.;Perlemuter, G.
目的酒精中毒者肝损伤易感性存在个体差异。在酒精性肝病（ALD）中已经报道了肠道微生物群（IM）的改变，但它们在多大程度上仅仅是一种后果或原因尚不清楚。我们的目的是证明，一个特定的生态失调有助于酒精性肝炎（AH）的发展。设计我们人源化无菌和常规小鼠使用人类IM移植从酒精患者有或没有AH。对酒精喂养的受体小鼠的后果studyed.Results一个特定的生态失调与ALD患者的严重程度。携带严重AH患者IM（sAH）的小鼠比携带无AH酒精患者IM（noAH）的小鼠发生更严重的肝脏炎症，肝脏T淋巴细胞亚群和自然杀伤T（NKT）淋巴细胞数量增加，肝坏死程度更高，肠道通透性更高，细菌易位更高。同样，内脏脂肪组织中的CD45+淋巴细胞亚群增加，肠系膜淋巴结中的CD4（+）T和NKT淋巴细胞增加。与sAH和noAH相关的IM可以通过细菌丰度和组成的差异来区分。关键有害物种与sAH相关，而粪杆菌属与noAH相关。熊去氧胆酸在noAH小鼠粪便中更丰富。此外，在传统的小鼠人源化与IM从sAH患者，第二个随后转移IM从noAH患者改善酒精诱导的肝lesions.Conclusions个体ALD的易感性基本上是由IM驱动。因此，可以通过IM操作来预防和管理ALD。
Objective There is substantial inter-individual diversity in the susceptibility of alcoholics to liver injury. Alterations of intestinal microbiota (IM) have been reported in alcoholic liver disease (ALD), but the extent to which they are merely a consequence or a cause is unknown. We aimed to demonstrate that a specific dysbiosis contributes to the development of alcoholic hepatitis (AH).Design We humanised germ-free and conventional mice using human IM transplant from alcoholic patients with or without AH. The consequences on alcohol-fed recipient mice were studied.Results A specific dysbiosis was associated with ALD severity in patients. Mice harbouring the IM from a patient with severe AH (sAH) developed more severe liver inflammation with an increased number of liver T lymphocyte subsets and Natural Killer T (NKT) lymphocytes, higher liver necrosis, greater intestinal permeability and higher translocation of bacteria than mice harbouring the IM from an alcoholic patient without AH (noAH). Similarly, CD45+ lymphocyte subsets were increased in visceral adipose tissue, and CD4(+) T and NKT lymphocytes in mesenteric lymph nodes. The IM associated with sAH and noAH could be distinguished by differences in bacterial abundance and composition. Key deleterious species were associated with sAH while the Faecalibacterium genus was associated with noAH. Ursodeoxycholic acid was more abundant in faeces from noAH mice. Additionally, in conventional mice humanised with the IM from an sAH patient, a second subsequent transfer of IM from an noAH patient improved alcohol-induced liver lesions.Conclusions Individual susceptibility to ALD is substantially driven by IM. It may, therefore, be possible to prevent and manage ALD by IM manipulation.