Wulingsan alleviates metabolic dysfunction-associated steatotic liver disease through regulating gut microbiota-bile acid axis

IF 2.6 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Prostaglandins & other lipid mediators Pub Date : 2026-03-01 Epub Date: 2026-03-08 DOI:10.1016/j.prostaglandins.2026.107067

Junyu Luo , Xiaowen Jin , Mingyue Cui , Hanyu He , Jiabao Liao , Weibo Wen , Wenting Li , Yongjun Cao

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引用次数: 0

Abstract

Background

Metabolic dysfunction-associated Steatotic Liver Disease (MASLD) is closely linked to gut microbiota disorders and bile acid imbalance. Wulingsan (WLS) have shown promise in regulating these pathways, but its mechanism of action unclear. This study aimed to evaluate the therapeutic effect of WLS on the rat MASLD model from the perspectives of intestinal microbiota composition and bile acid homeostasis.

Methods

The MASLD model was induced by a high-fat diet (HFD) and treated with different doses of WLS. Body weight and serum lipid profiles were monitored, inflammation were assessed to ELISA and RT-qPCR. H&E staining to evaluate histopathological changes. The 16S rRNA sequencing and LC-MS/MS analysis of gut microbiota composition and bile acid profiles. The fecal microbiota transplantation (FMT) experiment verified the effect of WLS on the gut microbiota.

Results

WLS treatment reduces the body weight of MASLD rats, improves lipid indicators, and inhibits inflammation and liver damage. The results of the FMT experiment indicated that transplantation of fecal microbiota from WLS-treated donors regulated the gut microbial composition and restored bile acid metabolic homeostasis in recipient rats.

Discussion

This study demonstrates that WLS treats MASLD by modulating multiple pathological pathways. Its effects in improving lipid metabolism and reducing hepatic inflammation align with the pathophysiological mechanisms of MASLD, indicating direct hepatoprotective actions. WLS intervention significantly restored gut microbiota diversity, increased the proportion of beneficial bacteria, suppressed potentially harmful bacterial genera, and corrected dysbiosis. FMT experiments further confirmed that gut microbes play a crucial role in mediating the therapeutic benefits of WLS. When microbiota from WLS-treated donors were transplanted into recipient rats, significant improvements were observed in metabolic markers, hepatic histopathology, and bile acid homeostasis. Collectively, the data support that WLS improves MASLD through a multi-targeted strategy centered on the gut-liver axis.

Conclusion

WLS has an effective therapeutic effect on MASLD by improving lipid metabolism, reducing liver inflammation, reshaping the intestinal microbiota and normalizing bile acid homeostasis.

查看原文本刊更多论文

五灵散通过调节肠道菌群-胆汁酸轴缓解代谢功能障碍相关的脂肪变性肝病。

背景：代谢功能障碍相关的脂肪变性肝病（MASLD）与肠道菌群紊乱和胆汁酸失衡密切相关。五灵散在调节这些通路方面显示出良好的前景，但其作用机制尚不清楚。本研究旨在从肠道菌群组成和胆汁酸稳态的角度评价枸杞多糖对大鼠MASLD模型的治疗作用。方法：采用高脂饲料（HFD）诱导MASLD模型，并用不同剂量的WLS处理。监测体重和血脂，采用ELISA和RT-qPCR检测炎症反应。H&E染色评价组织病理变化。16S rRNA测序和LC-MS/MS分析肠道菌群组成和胆汁酸谱。粪便菌群移植（FMT）实验验证了WLS对肠道菌群的影响。结果：WLS治疗可减轻MASLD大鼠体重，改善血脂指标，抑制炎症和肝损害。FMT实验结果表明，移植经wls处理的供体粪便微生物群可调节受体大鼠肠道微生物组成，恢复胆汁酸代谢稳态。讨论：本研究表明WLS通过调节多种病理通路治疗MASLD。其改善脂质代谢和减轻肝脏炎症的作用与MASLD的病理生理机制一致，表明其具有直接的肝保护作用。WLS干预显著恢复了肠道菌群多样性，增加了有益菌的比例，抑制了潜在的有害菌属，纠正了生态失调。FMT实验进一步证实，肠道微生物在介导WLS的治疗效果中起着至关重要的作用。当将来自经wls处理的供体的微生物群移植到受体大鼠体内时，在代谢标志物、肝脏组织病理学和胆汁酸稳态方面观察到显著改善。总的来说，数据支持WLS通过以肠-肝轴为中心的多目标策略改善MASLD。结论：WLS可改善脂质代谢，减轻肝脏炎症，重塑肠道菌群，调节胆汁酸稳态，对MASLD具有有效的治疗作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Prostaglandins & other lipid mediators 生物-生化与分子生物学

CiteScore

5.80

自引率

3.40%

发文量

审稿时长

2 months

期刊介绍： Prostaglandins & Other Lipid Mediators is the original and foremost journal dealing with prostaglandins and related lipid mediator substances. It includes basic and clinical studies related to the pharmacology, physiology, pathology and biochemistry of lipid mediators. Prostaglandins & Other Lipid Mediators invites reports of original research, mini-reviews, reviews, and methods articles in the basic and clinical aspects of all areas of lipid mediator research: cell biology, developmental biology, genetics, molecular biology, chemistry, biochemistry, physiology, pharmacology, endocrinology, biology, the medical sciences, and epidemiology. Prostaglandins & Other Lipid Mediators also accepts proposals for special issue topics. The Editors will make every effort to advise authors of the decision on the submitted manuscript within 3-4 weeks of receipt.