Table1_Chaihu Shugan prevents cholesterol gallstone formation by ameliorating the microbiota dysbiosis and metabolic disturbance in mice.XLSX

Introduction: Cholesterol gallstone (CGS) is a biliary tract disorder requiring treatment in approximately 20% of patients. The efficacy of Chaihu Shugan in preventing CGS recurrence after successful treatment remains uncertain.
Methods: We examined the in vivo preventive efficacy of Chaihu Shugan using a CGS mouse model and used multi-omics to study the interplay between gut microbiota, metabolism, and gene expression.
Results: The intestinal microbiota was severely dysregulated during the formation of CGS, showing a marked decrease in the abundance of beneficial microbiota, especially Lactobacillus and Akkermansia. Chaihu Shugan prevented CGS formation by restoring the composition of the gut microbiota and reversing the metabolic disturbances caused by dysbiosis. This preventive effect of Chaihu Shugan was paralleled by changes in the expression of metabolism-related genes in the liver. A network pharmacology analysis of Chaihu Shugan revealed that obacunone may be the key active metabolite in regulating bile acid metabolism. Multi-omics and correlation analyses elucidated the interplay between gut microbiota, metabolism, and gene alterations in the dose-dependent effect of Chaihu Shugan.
Conclusion: Our data show that Chaihu Shugan can prevent CGS and indicate its mechanisms of action.

引言：胆固醇胆囊结石（Cholesterol gallstone, CGS）是一类胆道疾病，约20%的患者需接受治疗。柴胡疏肝散（Chaihu Shugan）在成功治疗后预防CGS复发的疗效仍不明确。方法：本研究利用CGS小鼠模型评估柴胡疏肝散的体内预防功效，并采用多组学技术探究肠道菌群、代谢物与基因表达之间的相互调控关系。结果：在CGS形成过程中，肠道菌群严重失调，有益菌群丰度显著降低，尤其是乳杆菌属（Lactobacillus）与嗜黏蛋白阿克曼氏菌（Akkermansia）。柴胡疏肝散可通过恢复肠道菌群组成，逆转菌群失调引发的代谢紊乱，从而预防CGS的形成。该预防效应同时伴随肝脏代谢相关基因的表达改变。对柴胡疏肝散的网络药理学分析显示，黄柏酮（obacunone）可能是调控胆汁酸代谢的关键活性代谢物。多组学与关联分析阐明了柴胡疏肝散剂量依赖性效应中，肠道菌群、代谢状态与基因改变之间的互作机制。结论：本研究数据表明柴胡疏肝散可预防CGS，并揭示了其作用机制。