Table 2_Gandouling ameliorates Wilson’s disease-associated liver fibrosis in mice with associated faecal microbiome and metabolome remodeling.xlsx

IntroductionIndividuals with Wilson's disease (WD) exhibit liver fibrosis, a basic pathological change that was recently demonstrated to be dynamic and reversible. The gut microbiota markedly influences the occurrence of WD. Gandouling (GDL), a standardized Chinese herbal formula, has demonstrated an anti-fibrotic effect against WD-associated liver fibrosis. We sought to determine whether GDL may prevent liver fibrosis in toxic milk (TX) mice by assessing its ability to regulate gut microbiota, metabolites, and barrier function.
MethodsTX male mice aged 6 months were analysed. GDL was administered at varying doses over a 6-week period. The biochemical indexes related to liver function, fibrosis, and inflammation were determined using commercial assay kits. Histological analyses and immunohistochemistry staining, were performed to evaluate the histopathological changes and collagen deposition in mouse liver tissues. Additionally, to detect alterations in the intestinal bacterial composition and metabolites, faecal samples were examined using non-targeted metabolomics and 16S rRNA sequencing.
ResultsThe administration of GDL demonstrated anti-fibrotic effects on the liver, decreased serum inflammatory markers, ameliorated liver histopathology, and restored ileal permeability in the model group, as compared to the control group. Furthermore, a medium dosage of GDL treatment significantly rebalance microbiota composition and function and modulated lipid and lipid-like molecule levels.
DiscussionModulating intestinal homeostasis is a promising approach for treating liver fibrosis in patients with WD. Therefore, GDL may serve as a useful agent for treating WD-associated liver fibrosis.

引言：威尔逊病（Wilson's disease, WD）患者会出现肝纤维化，这一基础病理变化近期被证实具有动态性与可逆性。肠道菌群对威尔逊病的发生发展具有显著影响。肝豆灵（Gandouling, GDL）是一种标准化中药复方，其对WD相关肝纤维化展现出明确的抗纤维化作用。本研究旨在探讨肝豆灵是否可通过调控肠道菌群、代谢物及肠道屏障功能，预防有毒乳（toxic milk, TX）小鼠的肝纤维化。

方法：本研究选用6月龄的雄性有毒乳小鼠开展实验。实验周期为6周，以不同剂量给予肝豆灵干预。采用商业化检测试剂盒测定肝功能、纤维化及炎症相关的生化指标。通过组织学分析与免疫组化染色，评估小鼠肝组织的病理变化与胶原沉积情况。此外，采用非靶向代谢组学与16S rRNA测序技术分析粪便样本，以检测肠道菌群组成及代谢物的变化。

结果：相较于对照组，模型组小鼠经肝豆灵干预后可展现出肝脏抗纤维化作用，降低血清炎症标志物水平，改善肝脏组织病理学状态，并恢复回肠屏障通透性。此外，中剂量肝豆灵处理可显著重塑菌群组成与功能，并调节脂质及类脂质分子的水平。

讨论：调控肠道稳态是治疗威尔逊病患者肝纤维化的极具前景的策略。因此，肝豆灵或可成为治疗WD相关肝纤维化的有效干预制剂。