Polysaccharide NAP-3 Synergistically Enhances the Efficiency of Metformin in Type 2 Diabetes via Bile Acid/GLP-1 Axis through Gut Microbiota Remodeling,Journal of Agricultural and Food Chemistry

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Polysaccharide NAP-3 Synergistically Enhances the Efficiency of Metformin in Type 2 Diabetes via Bile Acid/GLP-1 Axis through Gut Microbiota Remodeling
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-09-11 , DOI: 10.1021/acs.jafc.4c06030
Lu Sun ₁ , Jiang Jiang ₁ , Yan Zeng ₁ , Jie Zhu ₁ , Suilou Wang ₁ , Dechun Huang ₁ , Chongjiang Cao ₁

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The polysaccharides of edible mushrooms are excellent phytochemicals for adjuvant treatment of metabolic diseases, but the potential mechanisms of synergistic effects are unclear. In this work, we discovered that NAP-3 enhanced the efficiency of metformin in lipid and glucose metabolism in type 2 diabetic (T2D) mice in a gut microbiome-dependent way. NAP-3 remodeled the intestinal microbial, resulting in the decreased activity of bile salt hydrolases and upregulation of CYP27A1 and CYP7B1 functions in the alternative pathway of bile acid synthesis, which leads to accumulation of the conjugated bile acids in ileum, specifically TβMCA and TUDCA. The accumulated conjugated bile acids either blocked or stimulated the nuclear receptors Farnesoid-X-receptor and TGR5, inducing the release of GLP-1 and ultimately enhanced glucose metabolism in mice. Collectively, our research indicated that edible mushroom polysaccharide NAP-3 may serve as a promising adjunctive oral therapeutic agent for T2D.

中文翻译：

多糖 NAP-3 通过肠道微生物群重塑通过胆汁酸/GLP-1 轴协同增强二甲双胍治疗 2 型糖尿病的功效

食用菌多糖是辅助治疗代谢性疾病的优良植物化学物质，但其协同作用的潜在机制尚不清楚。在这项工作中，我们发现 NAP-3 以肠道微生物组依赖性方式增强了二甲双胍在 2 型糖尿病 (T2D) 小鼠脂质和葡萄糖代谢中的效率。 NAP-3重塑肠道微生物，导致胆汁盐水解酶活性降低，胆汁酸合成替代途径中CYP27A1和CYP7B1功能上调，导致回肠中结合胆汁酸的积累，特别是TβMCA和TUDCA。积累的结合胆汁酸会阻断或刺激核受体Farnesoid-X-受体和TGR5，诱导GLP-1的释放，最终增强小鼠的葡萄糖代谢。总的来说，我们的研究表明，食用菌多糖 NAP-3 可能作为一种有前途的 T2D 辅助口服治疗剂。

更新日期：2024-09-11

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