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

Jielong Guo; Xue Han; Hongyu Tan; Weidong Huang; Yilin You; Jicheng Zhan

doi:10.1016/j.isci.2019.08.020

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

iScience. 2019 Sep 27:19:676-690. doi: 10.1016/j.isci.2019.08.020. Epub 2019 Aug 16.

Authors

Jielong Guo¹, Xue Han², Hongyu Tan², Weidong Huang³, Yilin You⁴, Jicheng Zhan⁵

Affiliations

¹ College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing 100083, China; Xinghua Industrial Research Centre for Food Science and Human Health, China Agricultural University, Xinghua 225700, Jiangsu, China.
² College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing 100083, China.
³ College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing 100083, China. Electronic address: huanggwd@263.net.
⁴ College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing 100083, China; Xinghua Industrial Research Centre for Food Science and Human Health, China Agricultural University, Xinghua 225700, Jiangsu, China. Electronic address: yilinyou@cau.edu.cn.
⁵ College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing 100083, China. Electronic address: zhanjicheng@cau.edu.cn.

Abstract

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.

Keywords: Microbiome; Nutrition; Obesity Medicine.