Characterizing the Sulfated and Glucuronidated (Poly)phenol Metabolome for Dietary Biomarker Discovery

Ioanna Tsiara; Belén Hervás Povo; Wafa Alotaibi; Paul Young Tie Yang; Ana Rodriguez-Mateos; Daniel Globisch

doi:10.1021/acs.jafc.4c12596

Characterizing the Sulfated and Glucuronidated (Poly)phenol Metabolome for Dietary Biomarker Discovery

Ioanna Tsiara, Belén Hervás Povo, Wafa Alotaibi, Paul Young Tie Yang, Ana Rodriguez-Mateos, Daniel Globisch

Nutritional Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

(Poly)phenols, bioactive compounds abundant in plant-based diets, have attracted interest for their potential role in preventing chronic diseases including cardiometabolic and neurodegenerative diseases. This study investigates the global sulfatome and glucuronidated metabolome in urine samples from 100 healthy adults collected pre- and postintervention following a 3-day (poly)phenol-rich intervention consisting of flaxseeds, raspberry powder, and soy milk. Using untargeted mass spectrometric metabolomics combined with selective phase II enzymatic treatment, we detected 156 sulfated and 143 glucuronidated metabolites in urine samples. Significant changes postintervention were observed for 91 sulfates and 94 glucuronides. Receiver operating characteristic curve analysis identified a combination of six polyphenol-derived key metabolites: glucuronidated daidzein and the sulfated compounds of pyrogallol, ferulic acid, 4-methoxyphenol, enterolactone, and resorcinol, which resulted in the best combination with the highest predictive AUC of 0.97. These findings underscore the utility of these metabolites as sensitive and selective biomarkers of (poly)phenol dietary intake.

Original language	English
Journal	JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
DOIs	https://doi.org/10.1021/acs.jafc.4c12596
Publication status	E-pub ahead of print - 2 Mar 2025

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title = "Characterizing the Sulfated and Glucuronidated (Poly)phenol Metabolome for Dietary Biomarker Discovery",

abstract = "(Poly)phenols, bioactive compounds abundant in plant-based diets, have attracted interest for their potential role in preventing chronic diseases including cardiometabolic and neurodegenerative diseases. This study investigates the global sulfatome and glucuronidated metabolome in urine samples from 100 healthy adults collected pre- and postintervention following a 3-day (poly)phenol-rich intervention consisting of flaxseeds, raspberry powder, and soy milk. Using untargeted mass spectrometric metabolomics combined with selective phase II enzymatic treatment, we detected 156 sulfated and 143 glucuronidated metabolites in urine samples. Significant changes postintervention were observed for 91 sulfates and 94 glucuronides. Receiver operating characteristic curve analysis identified a combination of six polyphenol-derived key metabolites: glucuronidated daidzein and the sulfated compounds of pyrogallol, ferulic acid, 4-methoxyphenol, enterolactone, and resorcinol, which resulted in the best combination with the highest predictive AUC of 0.97. These findings underscore the utility of these metabolites as sensitive and selective biomarkers of (poly)phenol dietary intake.",

author = "Ioanna Tsiara and {Herv{\'a}s Povo}, Bel{\'e}n and Wafa Alotaibi and {Young Tie Yang}, Paul and Ana Rodriguez-Mateos and Daniel Globisch",

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T1 - Characterizing the Sulfated and Glucuronidated (Poly)phenol Metabolome for Dietary Biomarker Discovery

AU - Tsiara, Ioanna

AU - Hervás Povo, Belén

AU - Alotaibi, Wafa

AU - Young Tie Yang, Paul

AU - Rodriguez-Mateos, Ana

AU - Globisch, Daniel

PY - 2025/3/2

Y1 - 2025/3/2

N2 - (Poly)phenols, bioactive compounds abundant in plant-based diets, have attracted interest for their potential role in preventing chronic diseases including cardiometabolic and neurodegenerative diseases. This study investigates the global sulfatome and glucuronidated metabolome in urine samples from 100 healthy adults collected pre- and postintervention following a 3-day (poly)phenol-rich intervention consisting of flaxseeds, raspberry powder, and soy milk. Using untargeted mass spectrometric metabolomics combined with selective phase II enzymatic treatment, we detected 156 sulfated and 143 glucuronidated metabolites in urine samples. Significant changes postintervention were observed for 91 sulfates and 94 glucuronides. Receiver operating characteristic curve analysis identified a combination of six polyphenol-derived key metabolites: glucuronidated daidzein and the sulfated compounds of pyrogallol, ferulic acid, 4-methoxyphenol, enterolactone, and resorcinol, which resulted in the best combination with the highest predictive AUC of 0.97. These findings underscore the utility of these metabolites as sensitive and selective biomarkers of (poly)phenol dietary intake.

AB - (Poly)phenols, bioactive compounds abundant in plant-based diets, have attracted interest for their potential role in preventing chronic diseases including cardiometabolic and neurodegenerative diseases. This study investigates the global sulfatome and glucuronidated metabolome in urine samples from 100 healthy adults collected pre- and postintervention following a 3-day (poly)phenol-rich intervention consisting of flaxseeds, raspberry powder, and soy milk. Using untargeted mass spectrometric metabolomics combined with selective phase II enzymatic treatment, we detected 156 sulfated and 143 glucuronidated metabolites in urine samples. Significant changes postintervention were observed for 91 sulfates and 94 glucuronides. Receiver operating characteristic curve analysis identified a combination of six polyphenol-derived key metabolites: glucuronidated daidzein and the sulfated compounds of pyrogallol, ferulic acid, 4-methoxyphenol, enterolactone, and resorcinol, which resulted in the best combination with the highest predictive AUC of 0.97. These findings underscore the utility of these metabolites as sensitive and selective biomarkers of (poly)phenol dietary intake.

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SN - 0021-8561

JO - JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

JF - JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

ER -

Characterizing the Sulfated and Glucuronidated (Poly)phenol Metabolome for Dietary Biomarker Discovery

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