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阿卡波糖作为一种葡萄糖淀粉酶抑制剂,对小鼠肠道微生物组具有饮食依赖性和可恢复的作用。

The Glucoamylase Inhibitor Acarbose Has a Diet-Dependent and Reversible Effect on the Murine Gut Microbiome.

机构信息

Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA

出版信息

mSphere. 2019 Feb 6;4(1):e00528-18. doi: 10.1128/mSphere.00528-18.

Abstract

Acarbose is a safe and effective medication for type 2 diabetes that inhibits host glucoamylases to prevent starch digestion in the small intestines and thus decrease postprandial blood glucose levels. This results in an increase in dietary starch in the distal intestine, where it becomes food for the gut bacterial community. Here, we examined the effect of acarbose therapy on the gut community structure in mice fed either a high-starch (HS) or high-fiber diet rich in plant polysaccharides (PP). The fecal microbiota of animals consuming a low dose of acarbose (25 ppm) was not significantly different from that of control animals that did not receive acarbose. However, a high dose of acarbose (400 ppm) with the HS diet resulted in a substantial change to the microbiota structure. Most notably, the HS diet with a high dose of acarbose lead to an expansion of the and and a decrease in the (such as ) and the S24-7. Once acarbose treatment ceased, the community composition quickly reverted to mirror that of the control group, suggesting that acarbose does not irreversibly alter the gut community. The high dose of acarbose in the PP diet resulted in a distinct community structure with increased representation of and Short-chain fatty acids (SCFAs) measured from stool samples were increased, especially butyrate, as a result of acarbose treatment in both diets. These data demonstrate the potential of acarbose to change the gut community structure and increase beneficial SCFA output in a diet-dependent manner. The gut microbial community has a profound influence on host physiology in both health and disease. In diabetic individuals, the gut microbiota can affect the course of disease, and some medications for diabetes, including metformin, seem to elicit some of their benefits via an interaction with the microbiota. Here, we report that acarbose, a glucoamylase inhibitor for type 2 diabetes, changes the murine gut bacterial community structure in a reversible and diet-dependent manner. In both high-starch and high-fiber diet backgrounds, acarbose treatment results in increased short-chain fatty acids, particularly butyrate, as measured in stool samples. As we learn more about how human disease is affected by the intestinal bacterial community, the interplay between medications such as acarbose and the diet will become increasingly important to evaluate.

摘要

阿卡波糖是一种安全有效的 2 型糖尿病药物,它通过抑制宿主的葡萄糖淀粉酶来阻止小肠中淀粉的消化,从而降低餐后血糖水平。这导致膳食淀粉在回肠远端增加,成为肠道细菌群落的食物。在这里,我们研究了阿卡波糖治疗对喂食高淀粉(HS)或富含植物多糖的高纤维饮食(PP)的小鼠肠道群落结构的影响。摄入低剂量(25ppm)阿卡波糖的动物的粪便微生物群与未接受阿卡波糖的对照动物没有显著差异。然而,高剂量(400ppm)的阿卡波糖与 HS 饮食相结合会导致微生物群结构发生重大变化。最值得注意的是,高剂量的 HS 饮食与阿卡波糖导致 和 扩张, 和 (如 )和 减少 S24-7。一旦停止阿卡波糖治疗,群落组成迅速恢复到对照组的状态,这表明阿卡波糖不会不可逆地改变肠道群落。PP 饮食中的高剂量阿卡波糖导致群落结构明显不同, 增加 和 短链脂肪酸(SCFAs)的测量来自粪便样本增加,尤其是丁酸盐,这是由于两种饮食中阿卡波糖的治疗。这些数据表明,阿卡波糖具有改变肠道群落结构并以饮食依赖的方式增加有益的 SCFA 输出的潜力。肠道微生物群落对健康和疾病中的宿主生理学有深远的影响。在糖尿病患者中,肠道微生物群可以影响疾病的进程,一些糖尿病药物,包括二甲双胍,似乎通过与微生物群的相互作用发挥了一些益处。在这里,我们报告说,阿卡波糖,一种 2 型糖尿病的葡萄糖淀粉酶抑制剂,以可逆和饮食依赖的方式改变了小鼠肠道细菌群落结构。在高淀粉和高纤维饮食背景下,阿卡波糖治疗导致粪便样本中短链脂肪酸(尤其是丁酸盐)增加。随着我们对肠道细菌群落如何影响人类疾病的了解越来越多,药物(如阿卡波糖)与饮食之间的相互作用将变得越来越重要,需要加以评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddeb/6365613/5510a6616f7a/mSphere.00528-18-f0001.jpg

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