N-Acetylcysteine alleviates gut dysbiosis and glucose metabolic disorder in high-fat diet-fed mice
N-乙酰半胱氨酸改善高脂饮食小鼠的肠道菌群失衡和糖代谢紊乱
Abstract
enBackground
N-Acetylcysteine (NAC), an antioxidative reagent for clinical diseases, shows potential in the treatment of diabetes and other metabolic diseases. However, it is unknown how NAC modulates the gut microbiota of mice with metabolic syndrome. The aim of the present study was to demonstrate the preventive effect of NAC on intestinal dysbiosis and glucose metabolic disorder.
Methods
Mice (C57BL/6J strain) were fed either a normal chow diet (NCD), NCD plus NAC, a high-fat diet (HFD), or HFD plus NAC for 5 months, after which glucose levels, circulating endotoxins and key metabolism-related proteins were determined. Fecal samples were analyzed by 16S rRNA sequencing. A novel analysis was performed to predict functional changes in gut microbiota. In addition, Spearman's correlation analysis was performed between metabolic biomarkers and bacterial abundance.
Results
Treatment with NAC significantly reversed the glucose intolerance, fasting glucose concentrations, and gains in body weight and plasma endotoxin in HFD-fed mice. Further, NAC upregulated occludin and mucin glycoprotein levels in the proximal colon of HFD-treated mice. Noticeably, NAC promoted the growth of beneficial bacteria (i.e. Akkermansia, Bifidobacterium, Lactobacillus and Allobaculum) and decreased populations of diabetes-related genera, including Desulfovibrio and Blautia. In addition, NAC may affect the metabolic pathways of intestinal bacteria, including lipopolysaccharide biosynthesis, oxidative stress, and bacterial motility. Finally, the modified gut microbiota was closely associated with the metabolic changes in NAC-treated HFD-fed mice.
Conclusions
N-Acetylcysteine may be a potential drug to prevent glucose metabolic disturbances by reshaping the structure of the gut microbiota.
Abstract
zh摘要
背景
临床上抗氧化药物N-乙酰半胱氨酸(N-Acetylcysteine,NAC)在治疗糖尿病和其他代谢疾病方面具有潜力。然而,NAC如何调节糖脂代谢综合征小鼠的肠道菌群并无报道。本项研究旨在揭示NAC对肠道菌群失衡和糖代谢紊乱的改善作用。
方法
C57BL/6J小鼠分别喂食正常饮食、正常饮食联合NAC、高脂饮食、高脂饮食联合NAC,为期5个月。之后对小鼠的血糖、循环内毒素和代谢相关的关键蛋白进行检测, 对粪便样品进行16S rRNA测序分析。利用一种新的分析方法预测菌群功能的改变。此外, 用Spearman关联分析法分析代谢标记物和菌群丰度之间的相关性。
结果
NAC处理可显著逆转高脂饮食小鼠的葡萄糖不耐受、空腹血糖、体重增加、血浆内毒素等指标。同时,NAC 上调了高脂饮食小鼠近端结肠的Occludin和粘蛋白水平。并且,NAC可显著促进有益菌(如Akkermansia、Bifidobacterium、Lactobacillus、Allobaculum等菌属)的增殖, 减少包括Desulfovibrio和Blautia等糖尿病相关菌属的含量。另外,NAC可能影响肠道细菌的代谢通路, 包括脂多糖生物合成、氧化应激、细菌运动。最后, 结果提示高脂饮食小鼠中NAC对肠道菌群的影响与代谢过程的改变紧密相关。
结论
N-乙酰半胱氨酸可能成为通过重塑肠道菌群结构从而改善糖代谢紊乱的潜在药物。
