Development of a method for preventing NASH progression and hepatocarcinogenesis by using butyrate-produding probiotics

采用CDAA饲料建立大鼠NASH模型。用含有10%MIYAIRI 588的CDAA饮食处理大鼠，MIYAIRI 588是C.酪酸，减少CDAA饮食诱导的肝脏脂质沉积，并显着改善甘油三酯含量，胰岛素抵抗，血清内毒素水平，和肝脏炎症指标。我们还发现MIYAIRI 588显著增加了肝脏AMPK和AKT和Nrf2及其靶向抗氧化酶的活化，从而抑制了肝脏氧化应激。体外研究表明，丁酸钠（NaB）激活AMPK和AKT，并增强Nrf2的表达。NaB介导的AMPK活化诱导Sirtuin 1的磷酸化和核转位，导致mTOR复合物2的组装增加和AKT的磷酸化，以及随后诱导Nrf2表达和活化。这些数据清楚地表明，产丁酸益生菌MIYIRI 588在预防NASH进展方面具有有益作用。

We used a CDAA diet to establish rat NASH model. Rats treated with CDAA diet containing 10% MIYAIRI588, a pharmaceutical product of C. butyricum, reduced CDAA-diet induced hepatic lipid deposition and significantly improved the triglyceride content, insulin resistance, serum endotoxin levels, and hepatic inflammatory indexes. We also found that MIYAIRI 588 substantially increased the activation of hepatic AMPK and AKT and Nrf2 and its targeted antioxidative enzymes, which suppressed hepatic oxidative stress. In vitro studies revealed that sodium butyrate (NaB) activated AMPK and AKT and enhanced Nrf2 expression. NaB-mediated AMPK activation induced the phosphorylation and nuclear translocation of Sirtuin 1, leading to the increased assembly of mTOR complex 2 and phosphorylation of AKT and subsequent induction of Nrf2 expression and activation. These data clearly showed that the butyrate-producing probiotic MIYIRI 588 has beneficial effects in the prevention of NASH progression.