Reduction of Subacute Endotoxemia Could Mediate Beneficial Effects of Vaccinium myrtillus in Metabolic Syndrome - a PBMC Gene Expression Study

Obesity and its consequences on cardiometabolic health have been associated to low-grade inflammation. Anthocyanins are anti-inflammatory compounds in diet, and the major group of polyphenols found in wild European blueberries, bilberries (Vaccinium myrtillus). We have studied the effects of a bilberry-rich diet on inflammation and gene expression profile in peripheral blood mononuclear cells (PBMCs) in subjects with features of the metabolic syndrome. In a randomized, controlled dietary intervention study the bilberry group (n=15) consumed bilberries or berry products equivalent to 400 g of fresh berries daily for 8 weeks, while the participants in the control group (n=12) maintained their habitual diets. Inflammatory markers were measured before and after the intervention. The microarray profiling was done from 3 subjects in the bilberry group and further QPCR expression analyses from all subjects in both groups at both timepoints. From 50 differentially expressed transcripts for mRNA (P<0.005), five candidate genes; WDSUB1, COX7B, RGS18, DAPP1 and TICAM1, were randomly selected for QPCR analyses. To further explore the interplay of dietary change and the affected pathways additional genes of LBP, TNFRSF12A, RIPK-1, Ly96 (MD2), TAB-2 (Toll-like receptor pathway); CD19, CD72 (B-cell receptor pathway) MMD, CCR2 (Monocyte and macrophage associated genes) were selected for QPCR analyses. Bilberries tended to decrease plasma concentrations of hsCRP, IL-6 and LPS (lipopolysaccharide, endotoxin). An inflammation score based on these markers and TNF-alpha showed different trends between the bilberry and control groups. These changes were accompanied by differential expression in PBMCs of MMD and CCR2, transcripts associated with monocyte activation and recruitment, respectively. Our results indicate that high regular bilberry intake may reduce endotoxemia and chronic inflammation, the latter especially by directing the immunity away from overactive innate cell mediated responsiveness. Bilberry consumption may therefore decrease the long term risk of cardiovascular and metabolic diseases.