Bioavailable Microbial Metabolites of Flavanols Demonstrate Highly Individualized Bioactivity on In Vitro β-Cell Functions Critical for Metabolic Health

Dietary flavanols are known for disease preventative properties but are often poorly absorbed. Gut microbiome flavanol metabolites are more bioavailable and may exert protective activities. Using metabolite mixtures extracted from the urine of rats supplemented with flavanols and treated with or wit...

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Main Authors: Emily S. Krueger, Laura E. Griffin, Joseph L. Beales, Trevor S. Lloyd, Nathan J. Brown, Weston S. Elison, Colin D. Kay, Andrew P. Neilson, Jeffery S. Tessem
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Metabolites
Subjects:
Online Access:https://www.mdpi.com/2218-1989/13/7/801
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author Emily S. Krueger
Laura E. Griffin
Joseph L. Beales
Trevor S. Lloyd
Nathan J. Brown
Weston S. Elison
Colin D. Kay
Andrew P. Neilson
Jeffery S. Tessem
author_facet Emily S. Krueger
Laura E. Griffin
Joseph L. Beales
Trevor S. Lloyd
Nathan J. Brown
Weston S. Elison
Colin D. Kay
Andrew P. Neilson
Jeffery S. Tessem
author_sort Emily S. Krueger
collection DOAJ
description Dietary flavanols are known for disease preventative properties but are often poorly absorbed. Gut microbiome flavanol metabolites are more bioavailable and may exert protective activities. Using metabolite mixtures extracted from the urine of rats supplemented with flavanols and treated with or without antibiotics, we investigated their effects on INS-1 832/13 β-cell glucose stimulated insulin secretion (GSIS) capacity. We measured insulin secretion under non-stimulatory (low) and stimulatory (high) glucose levels, insulin secretion fold induction, and total insulin content. We conducted treatment-level comparisons, individual-level dose responses, and a responder vs. non-responder predictive analysis of metabolite composition. While the first two analyses did not elucidate treatment effects, metabolites from 9 of the 28 animals demonstrated significant dose responses, regardless of treatment. Differentiation of responders vs. non-responder revealed that levels of native flavanols and valerolactones approached significance for predicting enhanced GSIS, regardless of treatment. Although treatment-level patterns were not discernable, we conclude that the high inter-individual variability shows that metabolite bioactivity on GSIS capacity is less related to flavanol supplementation or antibiotic treatment and may be more associated with the unique microbiome or metabolome of each animal. These findings suggest flavanol metabolite activities are individualized and point to the need for personalized nutrition practices.
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spelling doaj.art-481b63ebb9024b8cb45525249a7394d72023-11-18T20:27:23ZengMDPI AGMetabolites2218-19892023-06-0113780110.3390/metabo13070801Bioavailable Microbial Metabolites of Flavanols Demonstrate Highly Individualized Bioactivity on In Vitro β-Cell Functions Critical for Metabolic HealthEmily S. Krueger0Laura E. Griffin1Joseph L. Beales2Trevor S. Lloyd3Nathan J. Brown4Weston S. Elison5Colin D. Kay6Andrew P. Neilson7Jeffery S. Tessem8Department of Nutrition, Dietetics, and Food Science, Brigham Young University, Provo, UT 84602, USAPlants for Human Health Institute, Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Kannapolis, NC 28081, USADepartment of Nutrition, Dietetics, and Food Science, Brigham Young University, Provo, UT 84602, USADepartment of Nutrition, Dietetics, and Food Science, Brigham Young University, Provo, UT 84602, USADepartment of Nutrition, Dietetics, and Food Science, Brigham Young University, Provo, UT 84602, USADepartment of Nutrition, Dietetics, and Food Science, Brigham Young University, Provo, UT 84602, USAPlants for Human Health Institute, Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Kannapolis, NC 28081, USAPlants for Human Health Institute, Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Kannapolis, NC 28081, USADepartment of Nutrition, Dietetics, and Food Science, Brigham Young University, Provo, UT 84602, USADietary flavanols are known for disease preventative properties but are often poorly absorbed. Gut microbiome flavanol metabolites are more bioavailable and may exert protective activities. Using metabolite mixtures extracted from the urine of rats supplemented with flavanols and treated with or without antibiotics, we investigated their effects on INS-1 832/13 β-cell glucose stimulated insulin secretion (GSIS) capacity. We measured insulin secretion under non-stimulatory (low) and stimulatory (high) glucose levels, insulin secretion fold induction, and total insulin content. We conducted treatment-level comparisons, individual-level dose responses, and a responder vs. non-responder predictive analysis of metabolite composition. While the first two analyses did not elucidate treatment effects, metabolites from 9 of the 28 animals demonstrated significant dose responses, regardless of treatment. Differentiation of responders vs. non-responder revealed that levels of native flavanols and valerolactones approached significance for predicting enhanced GSIS, regardless of treatment. Although treatment-level patterns were not discernable, we conclude that the high inter-individual variability shows that metabolite bioactivity on GSIS capacity is less related to flavanol supplementation or antibiotic treatment and may be more associated with the unique microbiome or metabolome of each animal. These findings suggest flavanol metabolite activities are individualized and point to the need for personalized nutrition practices.https://www.mdpi.com/2218-1989/13/7/801gut microbiomephytochemicalsflavanol metabolitesglucose sensitivityresponder analysispersonalized nutrition
spellingShingle Emily S. Krueger
Laura E. Griffin
Joseph L. Beales
Trevor S. Lloyd
Nathan J. Brown
Weston S. Elison
Colin D. Kay
Andrew P. Neilson
Jeffery S. Tessem
Bioavailable Microbial Metabolites of Flavanols Demonstrate Highly Individualized Bioactivity on In Vitro β-Cell Functions Critical for Metabolic Health
Metabolites
gut microbiome
phytochemicals
flavanol metabolites
glucose sensitivity
responder analysis
personalized nutrition
title Bioavailable Microbial Metabolites of Flavanols Demonstrate Highly Individualized Bioactivity on In Vitro β-Cell Functions Critical for Metabolic Health
title_full Bioavailable Microbial Metabolites of Flavanols Demonstrate Highly Individualized Bioactivity on In Vitro β-Cell Functions Critical for Metabolic Health
title_fullStr Bioavailable Microbial Metabolites of Flavanols Demonstrate Highly Individualized Bioactivity on In Vitro β-Cell Functions Critical for Metabolic Health
title_full_unstemmed Bioavailable Microbial Metabolites of Flavanols Demonstrate Highly Individualized Bioactivity on In Vitro β-Cell Functions Critical for Metabolic Health
title_short Bioavailable Microbial Metabolites of Flavanols Demonstrate Highly Individualized Bioactivity on In Vitro β-Cell Functions Critical for Metabolic Health
title_sort bioavailable microbial metabolites of flavanols demonstrate highly individualized bioactivity on in vitro β cell functions critical for metabolic health
topic gut microbiome
phytochemicals
flavanol metabolites
glucose sensitivity
responder analysis
personalized nutrition
url https://www.mdpi.com/2218-1989/13/7/801
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