AST-120 Treatment Alters the Gut Microbiota Composition and Suppresses Hepatic Triglyceride Levels in Obese Mice

<b>Background:</b> The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide. The existence of a relationship between the microbiota and the pathology of hepatic steatosis is also becoming increasingly clear. AST-120, an oral spherical carbon adsorbent, has been shown to be useful for delaying dialysis initiation and improving uremic symptoms in patients with chronic kidney disease. However, little is known about the effect of AST-120 on fatty liver. <b>Methods:</b> AST-120 (5% w/w) was administrated to 6-week-old male <i>db/db</i> mice for 8 weeks. The body weight, blood glucose and food consumption were examined. Hepatic triglyceride (TG) levels, lipid droplets and epididymal fat cell size were measured. The gut microbiota compositions were investigated in feces and cecum. <b>Results:</b> Significant decreases of the hepatic weight and hepatic TG levels were observed in the AST-120-treated <i>db/db</i> mice. Furthermore, AST-120 treatment was also associated with a decrease of Bacteroidetes, increase of Firmicutes, and a reduced ratio of Bacteroidetes to Firmicutes (B/F ratio) in the feces in the <i>db/db</i> mice. The B/F ratio in the feces was correlated with the liver weight and area of the liver occupied by lipid droplets in the <i>db/db</i> mice. <b>Conclusions:</b> These data suggest that AST-120 treatment alters the composition of the fecal microbiota and suppresses hepatic TG levels in the <i>db/db</i> mice.

背景：非酒精性脂肪性肝病（nonalcoholic fatty liver disease, NAFLD）的全球患病率呈逐年上升趋势。微生物群与肝脏脂肪变性的病理机制之间的关联也愈发明晰。AST-120作为一种口服球形碳吸附剂，已被证实可延缓慢性肾脏病（chronic kidney disease, CKD）患者的透析启动时间，并改善其尿毒症症状。然而，目前关于AST-120对脂肪肝的作用却知之甚少。
方法：以5%重量比（w/w）的AST-120对6周龄雄性db/db小鼠灌胃给药，持续8周。检测小鼠的体重、血糖水平及食物摄入量。检测肝脏甘油三酯（triglyceride, TG）水平、脂滴形态及附睾脂肪细胞大小。收集粪便及盲肠内容物，分析肠道菌群组成。
结果：经AST-120处理的db/db小鼠，其肝脏重量及肝脏甘油三酯水平均显著降低。此外，AST-120给药还可使db/db小鼠粪便中的拟杆菌门（Bacteroidetes）丰度降低、厚壁菌门（Firmicutes）丰度升高，并降低拟杆菌门与厚壁菌门的比值（B/F ratio）。粪便中的B/F比值与db/db小鼠的肝脏重量及肝脏脂滴占据面积呈显著相关。
结论：本研究数据表明，AST-120给药可改变db/db小鼠的粪便菌群组成，并抑制其肝脏甘油三酯水平升高。