Park M-Y, Kim S J, Ko E K, Ahn S-H, Seo H, Sung M-K
Department of Food and Nutrition Education, Graduate School of Education, Soonchunhyang University, Asan, Chungnam, Korea.
Department of Food and Nutrition, Sookmyung Women's University, Seoul, Korea.
J Appl Microbiol. 2016 Sep;121(3):800-10. doi: 10.1111/jam.13158. Epub 2016 Jul 29.
Nonalcoholic hepatic fat accumulation has been hypothesized to be associated with alterations in gut microbiota composition, although mechanistic explanations for this link are largely insufficient. The aim of this study was to elucidate the microbiota-driven mechanisms involved in the development of nonalcoholic hepatic steatosis.
Ob/ob mice and their wild-type lean control mice were fed an AIN-93G diet for 12 weeks. Faecal microbiota composition, faecal bile acid (BA) profile and intestinal and hepatic markers of BA metabolism were analysed. Ob/ob mice had significantly less faecal taurine-conjugated BAs compared to their lean controls. The proportions of butyrate-producing bacteria were lower in ob/ob mice compared to those in lean mice. Intestinal expression of farnesoid X receptor (FXR) mRNA was significantly higher, whereas hepatic expression of cholesterol-7α-hydroxylase 1 (CYP7A1) and small heterodimer partner (SHP) were significantly lower in ob/ob mice compared to those in control mice.
Microbiota-associated BAs deconjugation may induce nonalcoholic fatty liver disease (NAFLD) by activating intestinal FXR signalling and blocking hepatic FXR-SHP pathway, thereby accelerating fat synthesis.
We provided evidences that changes in the gut microbiota and their metabolites can alter the profile of BAs, thereby providing a mechanism by which an altered microbiota profile contributes to the development of NAFLD.
尽管非酒精性肝脂肪堆积与肠道微生物群组成改变之间的机制解释大多不足，但已有假说认为二者存在关联。本研究旨在阐明微生物群驱动的非酒精性肝脂肪变性发生发展的机制。
给ob/ob小鼠及其野生型瘦对照小鼠喂食AIN-93G饮食12周。分析粪便微生物群组成、粪便胆汁酸（BA）谱以及BA代谢的肠道和肝脏标志物。与瘦对照小鼠相比，ob/ob小鼠的粪便牛磺酸结合型BA显著减少。与瘦小鼠相比，ob/ob小鼠中产生丁酸的细菌比例较低。与对照小鼠相比，ob/ob小鼠中类法尼醇X受体（FXR）mRNA的肠道表达显著升高，而胆固醇7α-羟化酶1（CYP7A1）和小异二聚体伴侣（SHP）的肝脏表达显著降低。
微生物群相关的BA去结合可能通过激活肠道FXR信号和阻断肝脏FXR-SHP途径诱导非酒精性脂肪性肝病（NAFLD），从而加速脂肪合成。
我们提供了证据表明肠道微生物群及其代谢产物的变化可改变BA谱，从而提供了一种改变的微生物群谱促成NAFLD发生发展的机制。
