Nonalcoholic fatty liver disease (NAFLD) is demonstrated to be closely related to the disorder of gut microbiota and the intestinal mucosal barrier. Luteolin is a natural flavonoid with various activities. We aimed to investigate whether Luteolin can alleviate NAFLD and its possible mechanism involving the gut-liver axis. A rat NAFLD model was established by feeding a high-fat diet (HFD), and Luteolin was administered intragastrically. The effects of Luteolin on liver biochemical parameters, intestinal histopathology and integrity, gut microbiota, lipopolysaccharides (LPS), inflammatory cytokines, and the Toll-like receptor 4 (TLR4) signaling pathway were evaluated. We found that Luteolin restored the expression of the tight junction proteins in the intestine and ameliorated the increase permeability of the intestinal mucosa to Fluorescein isothiocyanate-dextran (FD4) caused by a high-fat diet, thus enhancing the function of the intestinal barrier. In addition, Luteolin inhibited the TLR4 signaling pathway in the liver, thereby reducing the secretion of pro-inflammatory factors and alleviating NAFLD. 16S rRNA gene sequencing revealed that Luteolin intervention significantly altered the composition of the gut microbiota in NAFLD rats and increased the richness of gut microbiota. Luteolin alleviates NAFLD in rats via restoration and repair of the damaged intestinal mucosal barrier and microbiota imbalance.

非酒精性脂肪肝（NAFLD）已被证明与肠道菌群和肠粘膜屏障的紊乱密切相关。木犀草素是一种具有多种活性的天然黄酮类化合物。我们的目的是研究木犀草素是否可以缓解 NAFLD 及其涉及肠肝轴的可能机制。采用高脂饮食（HFD）喂养建立大鼠 NAFLD 模型，并灌胃木犀草素。评估了木犀草素对肝脏生化参数、肠道组织病理学和完整性、肠道微生物群、脂多糖 (LPS)、炎症细胞因子和 Toll 样受体 4 (TLR4) 信号通路的影响。我们发现木犀草素可以恢复肠道内紧密连接蛋白的表达，并改善高脂肪饮食引起的肠粘膜对异硫氰酸荧光素-葡聚糖（FD4）通透性的增加，从而增强肠道屏障的功能。此外，木犀草素还能抑制肝脏中的TLR4信号通路，从而减少促炎因子的分泌，缓解NAFLD。 16S rRNA 基因测序显示，木犀草素干预显着改变了 NAFLD 大鼠肠道微生物群的组成，并增加了肠道微生物群的丰富度。木犀草素通过恢复和修复受损的肠粘膜屏障和微生物群失衡来缓解大鼠 NAFLD。