4.7 Article

Dietary Blueberry Ameliorates Vascular Complications in Diabetic Mice Possibly through NOX4 and Modulates Composition and Functional Diversity of Gut Microbes

Journal

MOLECULAR NUTRITION & FOOD RESEARCH
Volume 66, Issue 8, Pages -

Publisher

WILEY
DOI: 10.1002/mnfr.202100784

Keywords

blueberry; diabetes; endothelial dysfunction; endothelium; gut microbiota; metabolites; vascular disease; vascular inflammation

Funding

  1. University of Utah Seed Grant
  2. College of Health Pilot Grant
  3. University of Utah Undergraduate Research Opportunities Program award
  4. Native American Research Internship
  5. University of Utah Summer Program for Undergraduate Research
  6. [NIH/NCCIH: R01AT010247]
  7. [USDA/NIFA: 2018-67018-27510]
  8. [USDA/NIFA: 2019-67017-29253]
  9. [NIH: R03AGO52848]
  10. [NIH/NHLBI: R01HL141540]
  11. [AHA16GRNT31050004]

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This study investigates the effects of dietary blueberries on vascular complications and gut microbiome in diabetic mice. The results show that blueberry supplementation can alleviate vascular inflammation, improve arterial endothelial function, and support the growth of commensal microbes.
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 I kappa K beta 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.

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