Matsushita N, Osaka T, Haruta I, Ueshiba H, Yanagisawa N, Omori-Miyake M, Hashimoto E, Shibata N, Tokushige K, Saito K, Tsuneda S, Yagi J
Support Center for Women Health Care Professionals and Researchers, Tokyo Women's Medical University, Tokyo, Japan.
Department of Medicine and Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
Scand J Immunol. 2016 Feb;83(2):109-18. doi: 10.1111/sji.12397.
The incidence of non-alcoholic steatohepatitis (NASH) is increasing. Because gut microbiota have been highlighted as one of the key factors in the pathogenesis of metabolic syndrome, we investigated the involvement of the bacterial component in the progression of non-alcoholic fatty liver (NAFL) to NASH. C57BL/6 mice were fed with maintenance food (MF, groups A and B) or a high caloric diet (HCD, groups C and D) for 1 month. Mice were then divided into four groups: Groups A and C were inoculated with PBS, while groups B and D were inoculated with lipopolysaccharide (LPS) plus complete Freund's adjuvant (CFA). The inoculations were performed a total of 3 times over 3 months. At 6 months, while hepatic steatosis was observed in groups C and D, cellular infiltration and fibrosis were less evident in group C than in group D. Inflammatory cytokines were upregulated in groups B and D. 16S rRNA pyrosequencing of whole colon homogenates containing faeces showed that certain bacterial groups, such as Bacteroidaceae, Peptostreptococcaceae and Erysipelotrichaceae, were increased in groups C and D. Although loading of bacterial components (LPS) resulted in hepatic inflammation in both MF- and HCD-fed mice, HCD feeding was more crucial in the progression of NAFL during the triggering phase.
非酒精性脂肪性肝炎（NASH）的发病率正在上升。由于肠道微生物群已被视为代谢综合征发病机制的关键因素之一，我们研究了细菌成分在非酒精性脂肪肝（NAFL）进展为NASH过程中的作用。将C57BL/6小鼠喂食维持食物（MF，A组和B组）或高热量饮食（HCD，C组和D组）1个月。然后将小鼠分为四组：A组和C组接种磷酸盐缓冲盐水（PBS），而B组和D组接种脂多糖（LPS）加完全弗氏佐剂（CFA）。在3个月内共进行3次接种。6个月时，虽然在C组和D组中观察到肝脏脂肪变性，但C组中的细胞浸润和纤维化比D组中更不明显。炎症细胞因子在B组和D组中上调。对含有粪便的全结肠匀浆进行16S rRNA焦磷酸测序显示，某些细菌类群，如拟杆菌科、消化链球菌科和丹毒丝菌科，在C组和D组中有所增加。尽管细菌成分（LPS）的注入在喂食MF和HCD的小鼠中均导致肝脏炎症，但在触发阶段，喂食HCD对NAFL的进展更为关键。
