N-Acetylcysteine alleviates gut dysbiosis and glucose metabolic disorder in high-fat diet-fed mice

Background: 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.