Zhu Zhiqin, Zhu Zhiqi, Shi Zhenyi, Wang Chen, Chen Fengsheng
Department of Hepatology, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, 510315, China.
School of Materials Science and Engineering, Central South University, Changsha, 410083, China.
Inflammation. 2024 Nov 12. doi: 10.1007/s10753-024-02184-2.
Changes in gut flora are associated with liver fibrosis. The interactions of host with intestinal flora are still unknown, with little research investigating such interactions with comprehensive multi-omics data. The present work analyzed and integrated large-scale multi-omics transcriptomics, microbiome, metabolome, and single-cell RNA-sequencing datasets from Kaempferol-treated and untreated control groups by advanced bioinformatics methods. This study concludes that kaempferol dose-dependently improved serum markers (like AST, ALT, TBil, Alb, and PT) and suppressed fibrosis markers (including HA, PC III, LN, α-SMA, and Collagen I), while kaempferol also increased body weight. Mechanistically, kaempferol improved the metabolic levels of intestinal flora dysbiosis and associated lipids. This was achieved by increasing the abundance of g__Robinsoniella, g__Erysipelotrichaceae_UCG-003, g__Coriobacteriaceae_UCG-002, and 5-Methylcytidine, all-trans-5,6- Epoxyretinoic acid, LPI (18:0), LPI (20:4), etc. to achieve this. Kaemferol exerts anti-inflammatory and immune-enhancing effects by down-regulating the Th17/IL-17 signaling pathway in PDGF-induced LX2 cells. In addition, kaempferol administration remarkably elevated CD4 + T and CD8 + T cellular proportions, thereby activating immune cells for protecting the body and controlling inflammatory conditions. The combined interaction of multiple data may explain how Kaempferol modulates the intestinal flora thereby remodeling the hepatocyte population and alleviating liver fibrosis.
肠道菌群的变化与肝纤维化相关。宿主与肠道菌群之间的相互作用仍不清楚，很少有研究使用全面的多组学数据来调查这种相互作用。本研究通过先进的生物信息学方法，分析并整合了来自山奈酚处理组和未处理对照组的大规模多组学转录组学、微生物组学、代谢组学和单细胞RNA测序数据集。本研究得出结论，山奈酚剂量依赖性地改善了血清标志物（如谷草转氨酶、谷丙转氨酶、总胆红素、白蛋白和凝血酶原时间），并抑制了纤维化标志物（包括透明质酸、Ⅲ型前胶原、层粘连蛋白、α-平滑肌肌动蛋白和Ⅰ型胶原蛋白），同时山奈酚还增加了体重。从机制上讲，山奈酚改善了肠道菌群失调和相关脂质的代谢水平。这是通过增加罗氏菌属、丹毒丝菌科UCG-003、棒状杆菌科UCG-002以及5-甲基胞苷、全反式-5,6-环氧视黄酸、溶血磷脂酰肌醇（18:0）、溶血磷脂酰肌醇（20:4）等的丰度来实现的。山奈酚通过下调血小板衍生生长因子诱导的LX2细胞中的Th17/IL-17信号通路发挥抗炎和免疫增强作用。此外，给予山奈酚显著提高了CD4+T和CD8+T细胞比例，从而激活免疫细胞以保护身体并控制炎症状态。多个数据的联合相互作用可能解释了山奈酚如何调节肠道菌群，从而重塑肝细胞群体并减轻肝纤维化。
