白及寡糖通过调节肠道菌群和宿主代谢缓解高脂饮食诱导的小鼠代谢相关脂肪性肝病
Bletilla striata oligosaccharides alleviate high-fat diet-induced metabolic associated fatty liver in mice through modulation of gut microbiota and host metabolism.
摘要(中文译文)
肠-肝轴功能障碍驱动代谢相关脂肪性肝病（MAFLD），但有效的治疗策略仍然有限。白及寡糖（BSO）具有免疫调节潜力，但其通过肠-肝轴在MAFLD中的作用尚不清楚。本研究旨在探讨BSO是否以及如何通过调节肠道菌群、肠道屏障功能和肝脏炎症来改善MAFLD。采用8周高脂饮食诱导小鼠MAFLD，随后通过灌胃给予BSO（150、300、600 mg/kg）或二甲双胍治疗12周。与MAFLD模型相比，高剂量BSO减少了体重增加，降低了空腹血糖，并降低了肝脏甘油三酯。BSO还减轻了肝损伤、肝脂肪变性和炎症。在机制上，BSO恢复了肠道屏障完整性，上调了结肠紧密连接蛋白，激活了结肠LXRα/ABCA1信号通路，同时抑制了肝脏TLR4/NF-κB通路。BSO重塑了肠道菌群，富集了有益的黑螺菌科和颤螺菌科，并调节了肝脏代谢物，表现为confertifoline减少以及D-肌醇-4-磷酸增加。此外，BSO激活了肠道FXR/FGF15轴并改善了胆汁酸代谢紊乱，表现为牛磺-ω-鼠胆酸和胆酸减少。本研究提供了系统性证据，表明BSO通过多靶点肠-肝轴机制缓解MAFLD，涉及肠道菌群重塑、屏障恢复、LXRα/ABCA1和FXR/FGF15信号通路的激活以及随后对肝脏TLR4/NF-κB驱动炎症的抑制。与既往方法相比，BSO具有良好的安全性特征和综合调节作用。这些发现支持BSO作为MAFLD治疗的有前景的候选药物，具有作为膳食补充剂或益生元制剂的潜在应用。
Abstract
Gut-liver axis dysfunction drives metabolic associated fatty liver disease (MAFLD), but effective therapeutic strategies remain limited. Bletilla striata oligosaccharides (BSO) have immunomodulatory potential, yet their role in MAFLD via the gut-liver axis is unclear. This study aimed to investigate whether and how BSO ameliorates MAFLD by modulating gut microbiota, intestinal barrier function, and hepatic inflammation. MAFLD was induced in mice by 8-week high-fat diet followed by 12-week BSO (150, 300, 600 mg/kg) or metformin treatment via oral gavage. Compared with the MAFLD model, high-dose BSO reduced body weight gain, lowered fasting glucose, and decreased hepatic triglycerides. BSO also attenuated liver injury, hepatic steatosis, inflammation. Mechanistically, BSO restored gut barrier integrity, upregulated colonic tight junction proteins, activated colonic LXRα/ABCA1 signaling, while suppressing the hepatic TLR4/NF-κB pathway. BSO remodeled gut microbiota, enriching beneficial Lachnospiraceae and Oscillospiraceae, and modulated hepatic metabolites, as shown by decreased confertifoline along with increased D-myo-inositol-4-phosphate. Additionally, BSO activated the intestinal FXR/FGF15 axis and ameliorated bile acid metabolism disorders, evidenced by reduced tauro-ω-muricholic acid and cholic acid. This study provides systematic evidence that BSO alleviates MAFLD through a multi-target gut-liver axis mechanism involving gut microbiota remodeling, barrier restoration, activation of LXRα/ABCA1 and FXR/FGF15 signaling, and subsequent suppression of hepatic TLR4/NF-κB-driven inflammation. Compared to previous approaches, BSO offers a favorable safety profile with combined regulatory effects. These findings support BSO as a promising candidate for MAFLD treatment, with potential applications as a dietary supplement or prebiotic agent.
如何引用
AMA
Kaiwen Lei, Jie Li, Kunhua Wei, Yan Bai, Jianwen Mao, Zhengquan Su. Bletilla striata oligosaccharides alleviate high-fat diet-induced metabolic associated fatty liver in mice through modulation of gut microbiota and host metabolism.. Frontiers in nutrition. 2026; doi:10.3389/fnut.2026.1852189.
APA
Kaiwen Lei, Jie Li, Kunhua Wei, Yan Bai, Jianwen Mao, Zhengquan Su (2026). Bletilla striata oligosaccharides alleviate high-fat diet-induced metabolic associated fatty liver in mice through modulation of gut microbiota and host metabolism.. Frontiers in nutrition. https://doi.org/10.3389/fnut.2026.1852189
GB/T 7714
Kaiwen Lei, Jie Li, Kunhua Wei, Yan Bai, Jianwen Mao, Zhengquan Su. Bletilla striata oligosaccharides alleviate high-fat diet-induced metabolic associated fatty liver in mice through modulation of gut microbiota and host metabolism.[J]. Frontiers in nutrition, 2026 doi:10.3389/fnut.2026.1852189.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出