Water-soluble Poria cocos polysaccharide improves alcoholic liver disease via modulation of gut microbiota-mediated intestinal bile acids-farnesoid X receptor.

IF 8.5 1区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biological Macromolecules Pub Date : 2025-10-09 DOI:10.1016/j.ijbiomac.2025.148202

Jiajing Huang, Luzhe Yu, Chen Zhang, Yue Fang, Xinyue Zhou, Rulin Wang, Lihua Xing, Lei Wang, Nianjun Yu, Daiyin Peng, Weidong Chen, Yue Zhang, Yanyan Wang

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Abstract

Alcoholic liver disease (ALD) is characterized by gut microbiota dysbiosis. This study aimed to elucidate the mechanism by which water-soluble Poria cocos polysaccharide (PCP) ameliorates ALD through modulation of the gut microbiota. PCP administration alleviated hepatic injury, reduced lipid accumulation, and attenuated inflammation in ALD mice. It also enhanced intestinal barrier integrity, as indicated by upregulation of tight junction proteins (ZO-1, Occludin, Claudin-1) and reduced lipopolysaccharide (LPS) levels. Additionally, PCP treatment remodeled the gut microbiota profile, characterized by a marked enrichment of Parabacteroides distasonis, which is associated with bile acid metabolism. Targeted metabolomics revealed PCP increased intestinal chenodeoxycholic acid (CDCA) and cholic acid (CA) levels, activating the intestinal farnesoid X receptor/fibroblast growth factor 15 (FXR/FGF15) axis while suppressing hepatic Cholesterol 7α-hydroxylase (CYP7A1), ultimately reducing systemic bile acids. Fecal microbiota transplantation confirmed gut microbiota-mediated protection, while intestinal FXR inhibition with glycine-β-muricholic acid (Gly-β-MCA) abolished PCP's therapeutic effects. These findings reveal that PCP ameliorates ALD by regulating the gut microbiota-bile acid-FXR axis, PCP as a promising natural therapeutic for ALD.

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水溶性茯苓多糖通过调节肠道菌群介导的肠道胆汁酸-法内酯X受体改善酒精性肝病。

酒精性肝病（ALD）以肠道菌群失调为特征。本研究旨在阐明水溶性茯苓多糖（PCP）通过调节肠道菌群改善ALD的机制。PCP给药可减轻ALD小鼠的肝损伤，减少脂质积累，减轻炎症。通过上调紧密连接蛋白（ZO-1, Occludin, Claudin-1）和降低脂多糖（LPS）水平，它还增强了肠屏障的完整性。此外，PCP治疗重塑了肠道微生物群，其特征是与胆酸代谢相关的副芽孢杆菌显著富集。靶向代谢组学显示，PCP增加肠道鹅去氧胆酸（CDCA）和胆酸（CA）水平，激活肠道farnesoid X受体/成纤维细胞生长因子15 （FXR/FGF15）轴，同时抑制肝脏胆固醇7α-羟化酶（CYP7A1），最终减少全身胆汁酸。粪便菌群移植证实了肠道菌群介导的保护作用，而甘氨酸-β-胆酸（Gly-β-MCA）对肠道FXR的抑制作用则取消了PCP的治疗作用。这些研究结果表明，PCP通过调节肠道微生物群-胆汁酸- fxr轴来改善ALD， PCP是一种有前景的ALD天然疗法。

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来源期刊

International Journal of Biological Macromolecules 生物-生化与分子生物学

CiteScore

13.70

自引率

9.80%

发文量

2728

审稿时长

64 days

期刊介绍： The International Journal of Biological Macromolecules is a well-established international journal dedicated to research on the chemical and biological aspects of natural macromolecules. Focusing on proteins, macromolecular carbohydrates, glycoproteins, proteoglycans, lignins, biological poly-acids, and nucleic acids, the journal presents the latest findings in molecular structure, properties, biological activities, interactions, modifications, and functional properties. Papers must offer new and novel insights, encompassing related model systems, structural conformational studies, theoretical developments, and analytical techniques. Each paper is required to primarily focus on at least one named biological macromolecule, reflected in the title, abstract, and text.