Anthocyanin Improves Glucose Homeostasis in Obese Mice via Regulation of Intestinal Microbiota and Barrier Function

Abstract

Abstract Objectives Anthocyanin (ACN) with low bioavailability possess anti-diabetic effect, the mechanism of the action remained unclear. This study aimed to investigate whether the anti-diabetic effects of anthocyanin were related to regulation of gut microbiota and epithelial barrier function. Methods Male C57Bl/6N mice were randomly assigned into 3 groups and fed chow, high fat/high sugar diet (HFHS, 45 kcal% fat, 17 kcal% sucrose) or HFHS + 0.4% anthocyanin for 8 weeks. Furthermore, a separate cohort of HFHS-fed C57Bl/6N mice were oral gavage with fecal microbiota from HFHS, HFHS + ACN and heat-killed fecal microbial from HFHS + ACN-fed donors (HK-ACN) for 4 weeks, The composition of gut microbiota, systemic inflammation, glucose homeostasis and intestinal barrier function were determined. Results The area under the curve (AUC) of the oral glucose tolerance test (GTT) and insulin tolerance test (ITT) in HFHS-fed mice were 61% and 79% higher than those in Chow-fed mice (P < 0.05). ACN supplementation improved HFHS-induced glucose intolerance in the GTT (P < 0.05) and restore insulin sensitivity in the ITT (P < 0.05). ACN supplementation also attenuated HFHS-induced systemic inflammation, intestinal permeability and metabolic endotoxemia (P < 0.05). In addition, ACN administration increased expression of epithelial barrier function genes ZO-1, Occludin and decreased inducible NO-synthase (iNOS) protein levels in intestine of HFHS-fed mice. Gut microbiota analysis showed that ACN greatly altered gut microbiota of HFHS-fed mice. Transplantation of the gut microbiota from ACN-fed mice, but not HFHS-fed or HK-ACN-fed mice, significantly improved intestinal epithelial barrier function, systemic inflammation and glucose homeostasis. Conclusions The present study demonstrated that ACN improves HFHS-induced impairment of glucose metabolism by regulating the gut microbiota and epithelial barrier functions. Funding Sources No funding sources to report.