创作:迟卉 审核:药农 2016年04月12日
  • 将患有严重肝炎(sAH)和无肝炎(noAH)者的肠道菌群移植给无菌小鼠;
  • sAH鼠肝脏炎症、T淋巴细胞亚群和自然杀伤T淋巴细胞数量、肝坏死、肠通透性及细菌易位比noAH鼠更严重;
  • 内脏脂肪组织中CD45+淋巴细胞亚群及肠系膜淋巴结中CD4+T和自然杀伤T淋巴细胞增多;
  • 可通过肠道菌群丰度和组成区分sAH和noAH,有害种属与sAH相关,粪杆菌属与noAH相关,noAH鼠粪便中熊去氧胆酸含量更高;
  • sAH移植的常规鼠再移植noAH患者菌群后肝损伤程度改善。
蓝灿辉 | 热心肠先生
Gut [IF:19.819]

Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease



2015-12-07, Article

Abstract & Authors:展开

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.

First Authors:
Marta Llopis

Correspondence Authors:
Anne-Marie Cassard-Doulcier,G Perlemuter

All Authors:
Marta Llopis,Anne-Marie Cassard-Doulcier,Laura Wrzosek,L Boschat,A Bruneau,Gladys Ferrere,V Puchois,Jean-Charles Martin,P Lepage,Tiphaine Le Roy,Lucas Lefevre,B Langelier,F Cailleux,A M González-Castro,Sylvie Rabot,Françoise Gaudin-Nomé,Hélène Agostini,S Prévot,D Berrebi,D Ciocan,C Jousse,S Naveau,Philippe Gerard,G Perlemuter