Blueberry Extract Improves Obesity through Regulation of the Gut Microbiota and Bile Acids via Pathways Involving FXR and TGR5

The metabolic improvement effect of blueberries has long been recognized, although its precise mechanism(s) remains obscure. Here, we show that phenolic blueberry extract (BE) treatment improved diet- and genetically induced metabolic syndromes, which were linked to increased energy expenditure in brown adipose tissue (BAT) and improved lipid metabolism in the liver via pathways involving the bile acid (BA) receptors TGR5 and FXR. These observations were strongly correlated with the regulation of BAs (e.g., a decrease in the FXR inhibitors TαMCA and TβMCA) and the gut microbiota (GM) (e.g., an expansion of Bifidobacteria and Lactobacillus), because antibiotic treatment completely blunted the regulation of the GM and BAs and the metabolic effects of BE. We also observed similar results in db/db mice. Furthermore, treating mouse primary cells derived from the liver and BAT with the combinations of BAs mimicking the in vivo alterations upon BE treatment mirrored the in vivo observations in mice.