Blueberry Supplementation Influences the Gut Microbiota, Inflammation, and Insulin Resistance in High-Fat-Diet-Fed Rats

J Nutr. 2018 Feb 1;148(2):209-219. doi: 10.1093/jn/nxx027.


Background: Gut microbiota dysbiosis has been linked to obesity-associated chronic inflammation. Microbiota manipulation may therefore affect obesity-related comorbidities. Blueberries are rich in anthocyanins, which have anti-inflammatory properties and may alter the gut microbiota.

Objective: We hypothesized that blueberry supplementation would alter the gut microbiota, reduce systemic inflammation, and improve insulin resistance in high-fat (HF)-diet-fed rats.

Methods: Twenty-four male Wistar rats (260-270 g; n = 8/group) were fed low-fat (LF; 10% fat), HF (45% fat), or HF with 10% by weight blueberry powder (HF_BB) diets for 8 wk. LF rats were fed ad libitum, whereas HF and HF_BB rats were pair-fed with diets matched for fiber and sugar contents. Glucose tolerance, microbiota composition (16S ribosomal RNA sequencing), intestinal integrity [villus height, gene expression of mucin 2 (Muc2) and β-defensin 2 (Defb2)], and inflammation (gene expression of proinflammatory cytokines) were assessed.

Results: Blueberry altered microbiota composition with an increase in Gammaproteobacteria abundance (P < 0.001) compared with LF and HF rats. HF feeding led to an ∼15% decrease in ileal villus height compared with LF rats (P < 0.05), which was restored by blueberry supplementation. Ileal gene expression of Muc2 was ∼150% higher in HF_BB rats compared with HF rats (P < 0.05), with expression in the LF group not being different from that in either the HF or HF_BB groups. Tumor necrosis factor α (Tnfa) and interleukin 1β (Il1b) gene expression in visceral fat was increased by HF feeding when compared with the LF group (by 300% and 500%, respectively; P < 0.05) and normalized by blueberry supplementation. Finally, blueberry improved markers of insulin sensitivity. Hepatic insulin receptor substrate 1 (IRS1) phosphorylation at serine 307:IRS1 ratio was ∼35% higher in HF rats compared with LF rats (P < 0.05) and HF_BB rats.

Conclusion: In HF-diet-fed male rats, blueberry supplementation led to compositional changes in the gut microbiota associated with improvements in systemic inflammation and insulin signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipose Tissue / drug effects
  • Animals
  • Anthocyanins / administration & dosage
  • Bacteria / classification
  • Blueberry Plants*
  • DNA, Bacterial / analysis
  • Diet, High-Fat / adverse effects*
  • Dietary Fiber / administration & dosage
  • Dietary Supplements
  • Fruit / chemistry
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / genetics
  • Glucose Tolerance Test
  • Inflammation / prevention & control*
  • Insulin Resistance / physiology*
  • Liver / drug effects
  • Male
  • Plant Extracts / administration & dosage*
  • Rats
  • Rats, Wistar
  • Sequence Analysis, DNA


  • Anthocyanins
  • DNA, Bacterial
  • Dietary Fiber
  • Plant Extracts