Bioactivity of Flavonoids Not Hindered by Poor Bioavailability
Flavonoids are dietary compounds with potential bioactive healing properties. Many flavonoids have poor bioavailability and thus low circulating concentrations in the blood.
New research has shown that unabsorbed flavonoids are metabolized by the gut microbiota to smaller metabolites, which are more bioavailable than their precursors. New data suggest that these metabolites and the native flavonoid compounds may exhibit complementary and synergistic activities in the body.
This raises the intriguing prospect that bioavailability of native dietary flavonoids may not be as critical of a limiting factor to bioactivity as previously thought.
Title: Common gut microbial metabolites of dietary flavonoids exert potent protective activities in β-cells and skeletal muscle cells
Author(s): Benjamin F. Bitner, Jason D. Ray, Kyle B. Kener, Jacob A. Herring, Josie A. Tueller, Deborah K. Johnson, Claudia M. Tellez Freitas, Dane W. Fausnacht, Mitchell E. Allen, Alexander H. Thomson, K. Scott Weber, Ryan P. McMillan, Matthew W. Hulver, David A. Brown, Jeffery S. Tessem, Andrew P. Neilson
Institution(s): Department of Nutrition, Dietetics and Food Science, Brigham Young University, S243 ESC Provo, UT 84602; Department of Microbiology and Molecular Biology, Brigham Young University, 3137 LSB Provo, UT 84602; Department of Human Nutrition, Foods and Exercise, Virginia Tech, 1981 Kraft Dr., Blacksburg, VA 24060; Metabolic Phenotyping Core Facility, Virginia Tech, 1981 Kraft Dr., Blacksburg, VA 24060; Virginia Tech Center for Drug Discovery, 800, West Campus Dr. Room 3111 Blacksburg, VA 24061; Department of Food Science and Technology, Virginia Tech, 1981 Kraft Dr., Blacksburg, VA 24060
Publication: The Journal of Nutritional Biochemistry
Date: 15 September 2018
Abstract: Flavonoids are dietary compounds with potential anti-diabetes activities. Many flavonoids have poor bioavailability and thus low circulating concentrations. Unabsorbed flavonoids are metabolized by the gut microbiota to smaller metabolites, which are more bioavailable than their precursors. The activities of these metabolites may be partly responsible for associations between flavonoids and health. However, these activities remain poorly understood. We investigated bioactivities of flavonoid microbial metabolites [hippuric acid (HA), homovanillic acid (HVA), and 5-phenylvaleric acid (5PVA)] in primary skeletal muscle and β-cells compared to a native flavonoid ([(−)-epicatechin, EC]. In muscle, EC was the most potent stimulator of glucose oxidation, while 5PVA and HA simulated glucose metabolism at 25 μM, and all compounds preserved mitochondrial function after insult. However, EC and the metabolites did not uncouple mitochonndrial respiration, with the exception of 5PVA at10 μM. In β-cells, all metabolites more potently enhanced glucose-stimulated insulin secretion (GSIS) compared to EC. Unlike EC, the metabolites appear to enhance GSIS without enhancing β-cell mitochondrial respiration or increasing expression of mitochondrial electron transport chain components, and with varying effects on β-cell insulin content. The present results demonstrate the activities of flavonoid microbial metabolites for preservation of β-cell function and glucose utilization. Additionally, our data suggest that metabolites and native compounds may act by distinct mechanisms, suggesting complementary and synergistic activities in vivo which warrant further investigation. This raises the intriguing prospect that bioavailability of native dietary flavonoids may not be as critical of a limiting factor to bioactivity as previously thought.
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