孙妍华,王天宇,何珊,等.褐藻糖胶调节肠道菌群改善2型糖尿病[J].中国海洋药物,2023,42(5):19-26.
褐藻糖胶调节肠道菌群改善2型糖尿病
Fucoidan Regulates Intestinal Flora to Improve Type 2 Diabetes
投稿时间:2022-06-23  修订日期:2022-08-04
DOI:10.13400/j.cnki.cjmd.2023.05.006
中文关键词:  褐藻糖胶  二型糖尿病  肠道菌群;乳杆菌属
English Keywords:Fucoidan  type 2 diabetes  intestinal flora  Lactobacillus
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作者单位E-mail
孙妍华 山东中医药大学 药学院 sunyanhua1126@163.com 
王天宇 山东中医药大学 药学院 1365105410@qq.com 
何珊* 山东中医药大学 药学院 heshan0627@163.com 
张秀云 山东中医药大学 药学院 zhangxiuyunsh@163.com 
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中文摘要:
      目的 探讨褐藻糖胶(fucoidan,FPS)对2型糖尿病(Type 2 diabetes millitus,T2DM)大鼠的疗效及肠道菌群的调节作用。方法 采用高脂饮食(high fat diet,HFD)联合链脲佐菌素(streptozotocin,STZ)诱导T2DM大鼠模型,灌胃给予FPS。给药2个月后取血清,测定空腹血糖(fasting blood glucose,FBG)、空腹胰岛素(fasting serum insulin,FINS)及血脂四项;取大鼠新鲜粪便样本进行16S r DNA测序,分析大鼠肠道菌群。结果 与空白组比较,模型组大鼠的FBG、FINS、血脂及肠道菌群都发生紊乱(P<0.05或P<0.01);与模型组相比,FPS给药可以明显改善大鼠FBG、FINS和血脂四项等指标。16S r DNA分析表明,FPS可以提高菌群Alpha多样性,如丰富度和多样性;Beta多样性分析表明,FPS与空白组更为接近,表明FPS可以显著改善T2DM大鼠粪便菌群的整体结构。物种组成方面,在门水平上,FPS显著增加厚壁菌门(Firmicutes)丰度,并降低拟杆菌门(Bacteroidetes)、放线菌门(Actinobacteria)和变形菌门(Proteobacteria)丰度;在属水平上,FPS显著富集乳杆菌属(Lactobacillus)和毛螺菌属(Lachnospiraceae-NK4A136-group),并降低拟杆菌属(Bacteroides)丰度。LEfSe分析表明乳杆菌属是FPS关键的差异菌种,Spearman相关性分析进一步表明乳杆菌属与FBG及TG呈显著负相关,并与HDL-C极显著正相关。结论 FPS可显著改善T2DM的糖脂代谢,其作用机制可能与调节肠道菌群,特别是与乳杆菌属密切相关。
English Summary:
      Objective To investigate the efficacy of fucoidan (FPS) on type 2 diabetes millitus (T2DM) rats and its modulaiton on the intestinal flora. Methods A high-fat (HFD) diet combined with streptozotocin (STZ) was used to induce T2DM rat model, and FPS was intragastrically administrated for 2 months. After administration, serum was collected to determine fasting glucose (FBG), fasting insulin (FINS) and lipids; 16S r DNA sequencing was performed on fecal samples to analyze the structure of rat intestinal flora. Results Compared with the normal group, FBG, FINS, blood lipids and intestinal flora of rats in the model group were disturbed (P<0.05 or P<0.01); compared with the model group, FPS administration significantly improved the indexes of FBG, FINS and lipid in rats. 16S r DNA analysis showed that FPS could improve the Alpha diversity of gut microbiota, including richness and diversity, and Beta diversity showed that FPS was more similar to the normal group, indicating that FPS could significantly improve the overall structure of the fecal flora in T2DM rats. In terms of species composition, at the phylum level, FPS significantly increased the abundance of Firmicutes and decreased the abundance of Bacteroidetes, Actinobacteria and Proteobacteria; at the genus level, FPS enriched Lactobacillus and Lachnospiraceae-NK4A136-group, and decreased the abundance of Bacteroides. LEfSe analysis indicated that Lactobacillus was the potential biomarkers for FPS, Spearman correlation analysis further showed that Lactobacillus was significantly negatively correlated with FBG and TG, and extremely significantly positively correlated with HDL-C. Conclusion FPS significantly improved glucolipid metabolism in T2DM, and its mechanism of action may be related to the regulation of intestinal flora, especially with Lactobacillus.
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