Elsevier

The Journal of Nutrition

Volume 148, Issue 2, February 2018, Pages 209-219
The Journal of Nutrition

Blueberry Supplementation Influences the Gut Microbiota, Inflammation, and Insulin Resistance in High-Fat-Diet–Fed Rats1

https://doi.org/10.1093/jn/nxx027Get rights and content
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Abstract

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.

Conclusions

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.

Key Words

blueberry
gut microbiota
intestinal epithelial barrier
inflammation
insulin signaling

Abbreviations

BW
body weight
Defb2
β-defensin 2
GLP1
glucagon-like peptide 1
GPR
G-protein-coupled receptor
HF
high fat
HF_BB
high fat with 10% blueberry
IRS1
insulin receptor substrate 1
LBP
LPS-binding pro-tein
LF
low fat
Muc2
mucin 2
p-IRS1 (Ser307)
insulin receptor substrate 1 phosphorylation at serine 307
Ppar
peroxisome proliferator-activated receptor
Tnfa
tumor necrosis factor α

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1

Supported by Agriculture and Food Research Initiative Competitive Grant 2014-67017-21757 from the US Department of AgricultureNational Institute of Food and Agriculture. We acknowledge the University of California, Davis, Host Mi-crobe Systems Biology Core Facility for microbiota sample preparation and sequencing, the Mayo Clinic Metabolomics Core and its supporting grants (U24DK100469 and UL1TR000135) for SCFA analysis, the Vanderbilt University.