Dietary Blueberries Improve Vascular Inflammation and Alter the Composition of the Gut Microbiome in Aged Mice

Background Aging is a risk factor for cardiovascular diseases, which are major causes of disability and mortality in the elderly. Endothelial dysfunction and an imbalanced gut microbial ecology play a pivotal role in aging‐associated vascular complications. Dietary change may be an effective strategy to improve vascular health. In this study, we tested the hypothesis that dietary blueberries ameliorate vascular complications and gut dysbiosis in aged mice. Methods Aged mice (17‐month‐old C57BL/6J male, Jackson Laboratory) were fed a control diet (O) or freeze‐dried wild blueberry powder supplemented diet (3.8% in diet) (OB) for 15 weeks. Young mice (2‐month‐old) consumed a control diet (Y) or blueberry supplemented diet (YB) for an identical duration. Based on normalization to body surface area, the blueberry dose is equivalent to 1.5 human servings of blueberry (~240 g) per day. Metabolic parameters, vascular function and vascular inflammation were assessed at the end of the treatment period. Vascular inflammation was assessed by measuring the binding of fluorescent labelled mouse monocytic WEHI78/24 cells to the vascular endothelium. Mesenteric arteries were used to assess vascular function using isometric procedures. Microbial profiling was done using 16s rRNA amplification. Results Metabolic parameters such as body weight, food intake and blood glucose were similar among the groups. Old mice (O) exhibited improved glucose tolerance compared to young mice (Y). Blueberry supplementation did not alter glucose tolerance in young (YB) or old mice (OB). O vs Y had increased monocyte binding to vascular endothelium indicating enhanced vascular inflammation, but this was reduced by blueberry supplementation in OB vs O. Endothelium‐dependent vasorelaxation to acetylcholine and endothelium‐independent vasorelaxation to sodium nitroprusside were similar among the groups. Microbial profiling indicated changes in the composition of gut microbiome among the groups. α‐diversity indices such as Chao and observed species were similar at the phylum level but were different at the genus level among groups. β‐diversity, which represents compositional differences among groups, was different at the phylum and genus levels. Further, the relative abundance of gut microbes at different taxa levels were altered between O vs Y and OB vs O mice. Importantly, the relative abundance of genera Candidatus Saccharimonas and Enterorhabdus were decreased whereas Muribaculum was increased in O vs Y mice. Blueberry supplementation improved the relative abundance of these three genera in OB vs O mice. Conclusion Blueberry supplementation improves aging induced vascular inflammation in C57BL/6J mice without altering the metabolic milieu indicating the direct effect of blueberries on vasculature. Our study also provides evidence for changes in the composition of gut microbiome which might mediate some of the effects of blueberry supplementation in aged mice.