Zuo Gaolong, Li Menghua, Guo Xiaoli, Wang Ling, Yao Yanyan, Huang Jian-An, Liu Zhonghua, Lin Yong
Key Laboratory of Tea Science of Ministry of Education and Co-Innovation Centre of Education Ministry for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, PR China; National Research Center of Engineering & Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, PR China.
Key Laboratory of Tea Science of Ministry of Education and Co-Innovation Centre of Education Ministry for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, PR China; National Research Center of Engineering & Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, PR China; Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops, Ministry of Agriculture and Rural Affairs of China, Hunan Agricultural University, Changsha 410128, PR China.
Food Res Int. 2025 May;209:116207. doi: 10.1016/j.foodres.2025.116207. Epub 2025 Mar 14.
Non-alcoholic fatty liver disease (NAFLD) is a prevalent disorder of excessive fat accumulation and inflammation in the liver that currently lacks effective therapeutic interventions. Fu brick tea (FBT) has been shown to ameliorate liver damage and modulate gut microbiota dysbiosis in NAFLD, but the potential mechanisms have not been comprehensively elucidated, especailly whether its hepatoprotective effects are determined to depend on the homeostasis of gut microbiota, intestinal barrier function and hepatic immune microenvironment. In this study, our results further demonstrated that FBT not only alleviated NAFLD symptoms and related endotoxemia in high-fat diet (HFD)-fed rats, but also attenuated intestinal barrier dysfunction and associated inflammation, also confirmed in Caco-2 cell experiment. Meanwhile, FBT intervention significantly relieved HFD-induced gut microbiota dysbiosis, characterized by increased diversity and composition, particularly facilitating beneficial microbes, including short chain fatty acids (SCFAs) and bile acids producers, such as Blautia and Fusicatenibacter, and inhibiting Gram-negative bacteria, such as Prevotella_9 and Phascolarctobacterium. Also, the gut microbiota-dependent hepatoprotective effects of FBT were verified by fecal microbiota transplantation (FMT) experiment. Thus, the beneficial moulation of gut microbiota altered by FBT in levels of SCFAs, bile acids and lipopolysaccharides, intestinal barrier function and TLR4/NF-κB pathway contributed to alleviate liver steatosis and inflammation. Additionally, the hepatoprotective effects of FBT was further demonstrated by suppressing Kupffer cell activation and regulating lipid metabolism using an ex vivo model of liver organoid. Therefore, FBT supplementation can maintain intenstinal homeostasis and remodel hepatic immune microenvironment to prevent NAFLD and associated endotoxemia.
非酒精性脂肪性肝病（NAFLD）是一种常见的肝脏疾病，其特征为肝脏中脂肪过度积累和炎症，目前缺乏有效的治疗干预措施。茯砖茶（FBT）已被证明可改善NAFLD中的肝损伤并调节肠道微生物群失调，但其潜在机制尚未得到全面阐明，尤其是其肝脏保护作用是否取决于肠道微生物群的稳态、肠道屏障功能和肝脏免疫微环境。在本研究中，我们的结果进一步表明，FBT不仅减轻了高脂饮食（HFD）喂养大鼠的NAFLD症状和相关内毒素血症，还减轻了肠道屏障功能障碍和相关炎症，这在Caco-2细胞实验中也得到了证实。同时，FBT干预显著缓解了HFD诱导的肠道微生物群失调，其特征是多样性和组成增加，特别是促进了有益微生物，包括短链脂肪酸（SCFAs）和胆汁酸产生菌，如布劳特氏菌属和梭菌属，同时抑制了革兰氏阴性菌，如普雷沃氏菌属9和考拉杆菌属。此外，通过粪便微生物群移植（FMT）实验验证了FBT对肠道微生物群的肝脏保护作用。因此，FBT改变的肠道微生物群在SCFAs、胆汁酸和脂多糖水平、肠道屏障功能和TLR4/NF-κB途径方面的有益调节有助于减轻肝脏脂肪变性和炎症。此外，通过使用肝脏类器官的体外模型抑制库普弗细胞活化和调节脂质代谢，进一步证明了FBT的肝脏保护作用。因此，补充FBT可以维持肠道稳态并重塑肝脏免疫微环境，以预防NAFLD和相关内毒素血症。
