Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation and inflammation. Epigallocatechin gallate (EGCG) has been proven to be effective against NAFLD, but its hepatoprotective mechanisms based on the “gut microbiota-barrier-liver axis” are still not fully understood. Herein, the results demonstrated that EGCG effectively ameliorated NAFLD phenotypes and metabolic disorders in rats fed a high-fat diet (HFD), and inhibited intestinal barrier dysfunction and inflammation, which is also supported in the experiment of Caco-2 cells. Moreover, EGCG could restore gut microbiota diversity and composition, particularly promoting beneficial microbes, including short-chain fatty acids (SCFAs) producers, such as Lactobacillus, and suppressing Gram-negative bacteria, such as Desulfovibrio. The microbial modulation raised SCFA levels, decreased lipopolysaccharide levels, inhibited the TLR4/NF-κB pathway, and strengthened intestinal barrier function via Nrf2 pathway activation, thereby alleviating liver steatosis and inflammation. Spearman’s correlation analysis showed that 24 key OTUs, negatively or positively associated with NAFLD and metabolic disorders, were also reshaped by EGCG. Our results suggested that a combinative improvement of EGCG on gut microbiota dysbiosis, intestinal barrier dysfunction, and inflammation might be a potential therapeutic target for NAFLD.

中文翻译：

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茶多酚表没食子儿茶素没食子酸酯通过调节肠道微生物群失调和减轻肠道屏障功能障碍和相关炎症来预防大鼠非酒精性脂肪肝和相关内毒素血症

非酒精性脂肪肝（NAFLD）的特点是脂肪堆积和炎症。表没食子儿茶素没食子酸酯（EGCG）已被证明对 NAFLD 有效，但其基于“肠道菌群-屏障-肝脏轴”的保肝机制仍不完全清楚。在此，结果表明，EGCG有效改善高脂饮食（HFD）大鼠的NAFLD表型和代谢紊乱，并抑制肠道屏障功能障碍和炎症，这在Caco-2细胞的实验中也得到了支持。此外，EGCG 可以恢复肠道微生物群的多样性和组成，特别是促进有益微生物，包括短链脂肪酸 (SCFA) 生产者，如乳酸菌，并抑制革兰氏阴性菌，如脱硫弧菌。微生物调节提高了 SCFA 水平，降低了脂多糖水平，抑制了 TLR4/NF-κB 通路，并通过 Nrf2 通路激活增强了肠道屏障功能，从而减轻了肝脏脂肪变性和炎症。 Spearman的相关分析表明，与NAFLD和代谢紊乱呈负相关或正相关的24个关键OTU也被EGCG重塑。我们的结果表明，EGCG 对肠道菌群失调、肠道屏障功能障碍和炎症的联合改善可能是 NAFLD 的潜在治疗靶点。