Berberis kansuensis extract alleviates type 2 diabetes in rats by regulating gut microbiota composition
Berberis kansuensis extract alleviates type 2 diabetes in rats by regulating gut microbiota composition
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甘肃小檗提取物通过调节肠道微生物群组成缓解大鼠 2 型糖尿病
DOI：
10.1016/j.jep.2021.113995
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发表时间：
2021
影响因子：
5.4
通讯作者：
Yi Zhang
中科院分区：
文献类型：
--
作者：
Tong Xu;Yiman Ge;Huan Du;Qi Li;Xinmei Xu;Huan Yi;Xinyue Wu;Tingting Kuang;Gang Fan;Yi Zhang
背景小柏树皮(BerberiskansuenssSchneid，BK)是治疗2型糖尿病的常用藏药。本研究的目的是明确肠道微生物区系在BK提取物抗糖尿病作用中的作用。材料与方法采用高脂饮食联合小剂量链脲佐菌素(45 mg/kg)建立T2D大鼠模型，每5天测量一次大鼠体重。测定空腹血糖、糖化血清蛋白、胰岛素抵抗指数、胰岛素敏感指数、脂多糖和3种炎症因子(肿瘤坏死因子-α、白介素1-β和白介素6)，以评价其抗糖尿病作用。此外，每天两次口服抗生素混合物(100 mg/kg新霉素、100 mg/kg氨苄西林和50 mg/kg甲硝唑)制备假无菌动物，以评估肠道微生物区系的作用。结果BK提取物能显著降低T2D大鼠体重、空腹血糖、糖化血红蛋白、HOMA-IR、内毒素、肿瘤坏死因子-α、IL-1β和IL-6水平，升高胰岛素抵抗指数。但当T2D大鼠肠道微生物区系受到抗生素干扰时，BK不能改善T2D大鼠的HOMA-IR和ISI水平。提示BK的抗糖尿病作用可能与肠道微生物区系有关。16S rRNA基因测序结果表明，BK能明显改善T2D大鼠肠道微生物区系紊乱。BK能显著增加T2D大鼠拟杆菌门和阿克曼假单胞菌属的数量和类杆菌/粘菌的比例，降低变形杆菌门和柯林氏杆菌属、[反式鲁米诺]菌群、志贺氏菌属、肠球菌属、梭杆菌属、霍尔德曼杆菌属和普雷沃特氏菌属的数量。相关分析显示阿克曼原菌与胰岛素抵抗指数呈正相关，而肠球菌、肠球菌、梭杆菌、霍尔德曼氏菌、普罗沃特拉菌与胰岛素抵抗指数呈正相关，与胰岛素抵抗指数呈正相关。结论白头翁提取物对T2D大鼠有良好的抗糖尿病作用。这种提取物发挥作用的机制至少部分与其对肠道微生物区系的调节有关。
BackgroundThe stem bark ofBerberiskansuensisSchneid (BK) is a commonly used Tibetan medicine for the treatment of type 2 diabetes (T2D). However, its therapeutic mechanisms remain unclear.Aim of the studyOur aim is to clarify the role of gut microbiota in the anti-diabetic activity of BK extract.Materials and methodsHigh fat diet combined with low-dose streptozotocin (45 mg/kg) was used to establish a T2D rat model, and the body weight of rats was measured every five days. Fasting blood glucose (FBG), glycosylated serum protein (GSP), insulin resistance index (HOMA-IR), insulin sensitivity index (ISI), lipopolysaccharide (LPS), and three inflammatory factors (TNF-α, IL-1 β and IL-6) were measured to evaluate the anti-diabetic activity of BK. Moreover, pseudo-germ-free animals were prepared by oral administration of an antibiotic mixture (100 mg/kg neomycin, 100 mg/kg ampicillin and 50 mg/kg metronidazole) twice per day for 6 days to assess the role of gut microbiota. Gut microbiota analysis was performed through 16S rRNA high-throughput sequencing method.ResultsAfter 30 days of administration, BK extract could significantly decrease the levels of body weight, FBG, GSP, HOMA-IR, LPS, TNF-α, IL-1β and IL-6, and increase ISI levels in T2D rats. However, when the gut microbiota of T2D rats was disturbed by antibiotics, BK could not improve HOMA-IR and ISI levels in T2D rats. The results indicated that the anti-diabetic effect of BK might depend on the gut microbiota. Moreover, sequencing of 16S rRNA genes demonstrated that BK could significantly improve the gut microbiota disorder of T2D rats. Specifically, BK increased the abundance of phyla Bacteroidetes and generaAkkermansiaand the ratio of Bacteroides/Firmicutes, while reducing the abundance of phyla Proteobacteria and generaCollinella,[Ruminococcus]_gauvreauii_Group,EscherichiaShigella,Enterococcus,Fusobacterium,Holdemanella, andPrevotella_9 in T2D rats. Additionally, correlation analysis revealed thatAkkermansiawas positively correlated with ISI, while[Ruminococcus]_gauvreauii_Group,Collinella,Escherichia Shigella,Enterococcus,Fusobacterium,HoldemanellaandPrevotella_9 were positively correlated with FBG, GSP, LPS, HOMA-IR, TNF-α, IL-1β, and IL-6.ConclusionBK extract has a good anti-diabetic effect on T2D rats. The mechanism by which this extract exerts its action is, at least partly, related to its regulation of gut microbiota.