Gut-liver axis mediated by endotoxin and innate immunity

非酒精性脂肪性肝炎的根本原因尚不清楚，但肠道菌群和内毒素是重要因素。我们评价了内毒素、肠道通透性和天然免疫在胆碱缺乏和氨基酸限定(CDAA)饮食大鼠肝纤维化发展中的致病作用。在这些大鼠中，显著的纤维化与肠道通透性增加、肝脏Toll样受体4(TLR4)mRNA、脂多糖结合蛋白(LBP)和肿瘤坏死因子-α(TNF-α)mRNA的发育增加有关。口服不可吸收的抗生素和熊去氧胆酸可以抑制肠道通透性和TLR4介导的炎症，最终抑制纤维化的进展。肠道-肝轴的调节可能成为预防人类脂肪性肝炎的新策略。

The underling cause of nonalcoholic steatohepatitis is still unlear, but intestinal bacterial flora and endotoxin are important factors. We evaluated pathogenic roles of endotoxin, intestinal permeability and innate immunity on the development of liver fibrosis in rats fed choline-deficient and amino acid-defined (CDAA) diet. In these rats, marked fibrosis was associated with increased intestinal permeability, augmented development of Toll-like recrptor 4 (TLR4) mRNA, lipopolysaccharide binding protein (LBP) mRNA and TNF-alpha mRNA in the liver. Oral administrations of nonabsorbable antibiotics for selective bowel decontamination and ursodeoxycholic acids were demonstrated to suppress intestinal permeability and TLR4 mediated inflammation and finally inhibit progression of fibrosis. Regulation of gut-liver axis may become a new strategy for prevention of human steatohepatitis.