Curr Dev Nutr. 2019 Jun ;3(Suppl 1). Epub 2019 Jun 13. PMID: 31224923
Anthocyanin Improves Glucose Homeostasis in Obese Mice via Beneficial Regulation of Intestinal Microbiota and Barrier Function (OR34-08-19).
Objectives: Anthocyanin (ACN) is a natural polyphenol with anti-diabetic effects. However, intact anthocyanin has low bioavailability and largely arrives unmetabolized in the colon, its mechanisms of action remain unclear. The intestinal microbiota dysbiosis and leaky gut contribute to the development of diet-induced type 2 diabetes. Therefore, we aim to investigate whether the anti-diabetic effects of anthocyanin were related to changes in the gut microbiota and epithelial barrier function.Methods: Male C57Bl/6 N mice were randomly assigned into 4 groups and pair-fed either a chow or high fat/high sugar diet (HFHS, 45 kcal% fat, 17 kcal% sucrose) +/1.0% anthocyanin for 8 weeks. Indices of systemic inflammation, parameters of glucose homeostasis and intestinal barrier function were determined. The composition of the gut microbiota was assessed by analysing 16S rRNA gene sequences with Illumina pyrosequencing. To ascertain the involvement of the gut microbiota in the anti-diabetic effects of anthocyanin. A separate cohort of HFHS-fed C57Bl/6 N mice were oral gavage administered with fecal microbiota from chow-fed donors, HFHS-fed donors, HFHS + ACN-fed donors and heat-killed fecal microbial from HFHS + ACN-fed donors (HK-ACN) for 8 weeks, followed by the same examination.Results: Relative to vehicle controls, ACN ingestion attenuated several effects of HFHS feeding, including glucose intolerance, insulin resistance and serum inflammatory markers. ACN ingestion reduced intestinal permeability and metabolic endotoxemia. These beneficial effects of ACN were associated with increased expression of genes involved in epithelial barrier function (ZO-1, occludin) and decreased inducible NO-synthase (iNOS) protein levels in ileum and colon of HFHS-fed mice. Gut microbiota analysis revealed that ACN ingestion induced profound alterations in the gut microbiome of HFHS-fed mice. Transplantation of the gut microbiome from ACN-fed mice, but not HFHS-fed or HK-ACN-fed mice, was sufficient to recapitulate the improvement in intestinal epithelial barrier function, systemic inflammation and glucose homeostasis observed with oral ACN treatment.Conclusions: These findings indicate that ACN-mediated changes in the gut microbiota and epithelial barrier function may play a predominant role in the mechanism of action of anthocyanin.Funding Sources: The State Key Program of National Natural Science Foundation of China [grant number 81730090].