Scope: In diabetes, endothelial inflammation and dysfunction play a pivotal role in the development of vascular disease. This study investigates the effect of dietary blueberries on vascular complications and gut microbiome in diabetic mice. Methods and Results: Seven-week-old diabetic db/db mice consume a standard diet (db/db) or a diet supplemented with 3.8% freeze-dried blueberry (db/db+BB) for 10 weeks. Control db/+ mice are fed a standard diet (db/+). Vascular inflammation is assessed by measuring monocyte binding to vasculature and inflammatory markers. Isometric tension procedures are used to assess mesenteric artery function. db/db mice exhibit enhanced vascular inflammation and reduced endothelial-dependent vasorelaxation as compared to db/+ mice, but these are improved in db/db+BB mice. Blueberry supplementation reduces the expression of NOX4 and I𝜿K𝜷 in the aortic vessel and vascular endothelial cells (ECs) isolated from db/db+BB compared to db/db mice. The blueberry metabolites serum reduces glucose and palmitate induced endothelial inflammation in mouse aortic ECs. Further, blueberry supplementation increases commensal microbes and modulates the functional potential of gut microbes in diabetic mice. Conclusion: Dietary blueberry suppresses vascular inflammation, attenuates arterial endothelial dysfunction, and supports the growth of commensal microbes in diabetic mice. The endothelial-specific vascular benefits of blueberries are mediated through NOX4 signaling.

Scope: Metabolic syndrome (MetS) alters the gut microbial ecology and increases the risk of cardiovascular disease. This study investigates whether strawberry consumption reduces vascular complications in an animal model of MetS and identifies whether this effect is associated with changes in the composition of gut microbes. Methods and results: Seven-week-old male mice consume diets with 10% (C) or 60% kcal from fat (high-fat diet fed mice; HF) for 12 weeks and subgroups are fed a 2.35% freeze-dried strawberry supplemented diet (C+SB or HF+SB). This nutritional dose is equivalent to ≈160 g of strawberry. After 12 weeks treatment, vascular inflammation is enhanced in HF versus C mice as shown by an increased monocyte binding to vasculature, elevated serum chemokines, and increased mRNA expression of inflammatory molecules. However, strawberry supplementation suppresses vascular inflammation in HF+SB versus HF mice. Metabolic variables, blood pressure, and indices of vascular function were similar among the groups. Further, the abundance of opportunistic microbe is decreased in HF+SB. Importantly, circulating chemokines are positively associated with opportunistic microbes and negatively associated with the commensal microbes (Bifidobacterium and Facalibaculum). Conclusion: Dietary strawberry decreases the abundance of opportunistic microbe and this is associated with a decrease in vascular inflammation resulting from MetS.

Ectopic ceramide accumulation in insulin-responsive tissues contributes to the development of obesity and impairs insulin sensitivity. Moreover, pharmacological inhibition of serine palmitoyl transferase (SPT), the first enzyme essential for ceramide biosynthesis using myriocin in rodents reduces body weight and improves insulin sensitivity and associated metabolic indices. Myriocin was originally extracted from fruiting bodies of the fungus Isaria sinclairii and has been found abundant in a number of closely related fungal species such as the Cordyceps. Myriocin is not approved for human use but extracts from Cordyceps are routinely consumed as part of traditional Chinese medication for the treatment of numerous diseases including diabetes. Herein, we screened commercially available extracts of Cordyceps currently being consumed by humans, to identify Cordyceps containing myriocin and test the efficacy of Cordyceps extract containing myriocin in obese mice to improve energy and glucose homeostasis. We demonstrate that commercially available Cordyceps contain variable amounts of myriocin and treatment of mice with a human equivalent dose of Cordyceps extract containing myriocin, reduces ceramide accrual, increases energy expenditure, prevents diet-induced obesity, improves glucose homeostasis and resolves hepatic steatosis. Mechanistically, these beneficial effects were due to increased adipose tissue browning/beiging, improved brown adipose tissue function and hepatic insulin sensitivity as well as alterations in the abundance of gut microbes such as Clostridium and Bilophila. Collectively, our data provide proof-of-principle that myriocin containing Cordyceps extract inhibit ceramide biosynthesis and attenuate metabolic impairments associated with obesity. Moreover, these studies identify commercially available Cordyceps as a readily available supplement to treat obesity and associated metabolic diseases.

Mol. Nutr. Food Res. 2022, 66, 202200112 DOI: https://doi.org/10.1002/mnfr.202200112 In article 2200112, Pon Velayutham Anandh Babu and co‐workers show that dietary supplementation of strawberries reduces vascular complications in an animal model of metabolic syndrome, which is associated with changes in gut microbiota composition.

Background Evidence from our lab and others showed the vascular beneficial effects of dietary blueberries. However, dose‐ and time‐dependent effect of dietary blueberries on vascular complications in diabetes and the role of gut microbes in mediating this effect are unknown. We hypothesize that gut microbes are associated with the dose‐ and time‐dependent vascular beneficial effects of dietary blueberries. Methods 7‐week‐old db/db male mice (Jackson Lab), a widely‐used type 2 diabetic animal model, were fed a diet with or without freeze‐dried wild blueberry powder (FD‐BB) for 4 or 8 or 12 weeks (D4, D8, and D12). Diets contained 0%, 1.23% (B1), 2.46% (B2) and 3.7% (B3) of FD‐BB, which is equivalent to 0, ½, 1, and 2 human servings of wild blueberries. Age‐matched, non‐diabetic db/+ mice fed a standard diet for 4 or 8 or 12 weeks (C4, C8, and C12) were used as controls. After the treatment period blood glucose, body composition, glucose tolerance, and insulin tolerance were assessed. Vascular inflammation was determined by the binding of fluorescent labelled mouse monocytic WEHI78/24 cells to vascular endothelium and mRNA expression of vascular inflammatory chemokines and adhesion molecules (IL8/KC, MCP1/JE, ICAM1, VCAM1 and E‐selectin). Microbial profiling of cecum was done by 16s rRNA amplification. Results Diabetic mice (D4, D8 and D12) had increased blood glucose, impaired glucose and insulin tolerance, increased body fat, decreased lean body mass, enhanced binding of monocytes to the aortic vessel, and increased expression of selected inflammatory molecules as compared to their respective control mice (C4, C8 and C12). Blueberry treatment at all levels didn’t improve the metabolic parameters in diabetic mice. However, 3.7% FD‐BB treatment reduced the binding of WEHI78/24 monocyte to vascular endothelium and suppressed the mRNA expression of selected inflammatory molecules in diabetic mice (D4B3 vs D4, D8B3 vs D8, and D12B3 vs D12). Microbial profiling showed an alteration in the relative abundance of gut microbes at different taxonomic levels in diabetic mice as compared to their respective control mice. At the genera level, 7, 9 and 10 genera were altered after 4‐, 8‐ and 12‐weeks treatment in diabetic vs control mice. Blueberry supplementation at different dosages improved the relative abundance of selected gut microbes in diabetic mice (>4 genera) at different time points. Specifically, blueberry treatment increased the abundance of commensal microbe Bifidobacterium and decreased the abundance of opportunistic Clostridium genera in diabetic mice. Conclusion The beneficial effects of dietary blueberries on diabetic vasculature and gut microbiome varies with the doses and duration of treatment. In the present study, a dose of 3.7% FD‐BB in diet (equivalent to 1.5 human servings) was shown to exert potential beneficial effects on diabetic vasculature and is associated with specific gut microbes.