Blueberry supplementation impacts gut microbiota, inflammatory profiles, and insulin sensitivity in high-fat fed rats

Obesity and insulin resistance are associated with chronic inflammation, which is believed to originate from the gastrointestinal (GI) tract. Changes in microbiota composition and an increase in circulating pro‐inflammatory endotoxin are notably associated with impaired glucose tolerance. Our objective was to determine whether blueberry supplementation could impact microbiota composition and systemic inflammation as well as glucose tolerance in high‐fat fed rats. Wistar rats (n=8/group) were fed low‐fat (LF, 10% fat), high‐fat (HF, 45% fat) or high‐fat with 10% blueberry (HF_BB) diets for 8 weeks. HF and HF_BB diets were isocolaric and animals were pair‐fed. All diets were matched for sugar and fiber contents. Compared to the LF diet, HF feeding resulted in increased adiposity and liver fat deposition in both HF and HF_BB rats. Blueberry supplementation altered the microbiota composition, with decreases in Firmicutes and Bacteroidetes and increases in Proteobacteria and Fusobacteria . Gammaproteobacteria were the most noticeable change in the HF_BB group. Along with these changes, GI barrier integrity was improved in HF_BB animals, characterized by a decrease in circulating lipopolysaccharide‐binding protein and increases in protective gene expression levels in the ileum (defensin β2 and mucin 2). Moreover, blueberry treatment significantly decreased systemic inflammation, characterized by a decrease in tumor necrosis factor α (TNFα) and interleukin‐6 protein levels in the liver and reduced TNFα and cluster of differentiation 11d (a macrophage infiltration marker) gene expression in visceral fat. Inflammation has been shown to affect insulin signaling and HF_BB rats showed improvements in glucose tolerance and insulin sensitivity. Glucose and insulin levels during an oral glucose tolerance test were significantly decreased in HF_BB rats. Additionally, blueberry treatment increased ileal glucagon‐like‐peptide‐1 expression and significantly down‐regulated the level of hepatic pSer307 IRS‐1/IRS‐1 ratio (insulin receptor substrate 1), which are associated with improved glucose tolerance and impaired insulin signaling, respectively. Taken together, these data showed a potential anti‐inflammatory effect of blueberry supplementation associated with improved glucose tolerance. These effects may result from the alleviation of metabolic endotoxemia and intestinal inflammation and the modulation of gut microbiota. Support or Funding Information This material is based upon work that is supported by the National Institute of Food and Agriculture, USDA, under award number 2014‐67017‐21757.