Metabolite Biomarkers Linking a High-Fiber Rye Intervention with Cardiometabolic Risk Factors: The RyeWeight Study
Journal article, 2025

Wholegrain rye, considered one of the cereals with the highest content of dietary fiber and bioactive compounds, has been linked with reduced risk of cardiometabolic diseases. Thus, biomarkers reflecting its intake and/or the metabolic effect after consumption are essential to better elucidate its health effects. Our aim was to identify plasma metabolite biomarkers associated with a high-fiber rye intervention and to assess the associations between these metabolites, gut microbiota composition, and cardiometabolic risk factors in a 12-week randomized controlled trial comparing a hypocaloric diet with high-fiber rye (n = 108) or refined wheat (n = 99) in participants with obesity. Rye intervention increased plasma concentrations of benzoxazinoids (DIBOA-S) and phenylacetamides (2-HPA-S and 2-HHPA-S), gut microbial metabolites (indolepropionic acid, 2-aminophenol, enterolactone sulfate, and enterolactone glucuronide), betainized compounds (pipecolic-betaine), phenolic acids (2,6-DHBA and gallic acid-4-sulfate), and diverse endogenous metabolites. Microbiota composition changes were increased Eubacterium xylanophilum and Agathobacter and decreased Ruminococcus torques and Romboutsia. Moreover, the intervention effect was mostly captured by changes in metabolites and gut microbiota compared to clinical variables. Gallic acid-4-sulfate and phenylacetamides were associated with reductions in weight, fat mass, BMI, or fasting insulin levels even after adjusting for plasma alkylresorcinols, used as markers for rye intake compliance. Altogether, these metabolites may constitute biomarkers of wholegrain rye cardiometabolic effects.

cardiometabolic health

metabolomics

wholegrain rye

randomized controlled trial

gutmicrobiota

biomarker

refined wheat

Author

Andrea Union Caballero

University of Barcelona

Institute of Health Carlos III

Tomas Merono

Institute of Health Carlos III

University of Barcelona

Sebastian Åberg

Chalmers, Life Sciences, Food and Nutrition Science

Elise Nordin

Chalmers, Life Sciences, Food and Nutrition Science

Johan Dicksved

Uppsala University

Alex Sanchez-Pla

University of Barcelona

Institute of Health Carlos III

Marta Cubedo

University of Barcelona

Institute of Health Carlos III

Francisco Carmona-Pontaque

Institute of Health Carlos III

University of Barcelona

Kia Noehr Iversen

Chalmers, Life Sciences, Food and Nutrition Science

Miriam Martinez-Huelamo

Institute of Health Carlos III

University of Barcelona

Anna Guadall

University of Barcelona

Institute of Health Carlos III

Rikard Landberg

Chalmers, Life Sciences, Food and Nutrition Science

Cristina Andres-Lacueva

University of Barcelona

Institute of Health Carlos III

Journal of Agricultural and Food Chemistry

0021-8561 (ISSN) 1520-5118 (eISSN)

Vol. 73 35 21869-21879

Discovery and valdiation of novel biomarkers of gut microbiota, diet and their interactions associated with type 2 diabetes risk

Swedish Research Council (VR) (2019-01264), 2020-01-01 -- 2022-12-31.

Subject Categories (SSIF 2025)

Food Science

Nutrition and Dietetics

DOI

10.1021/acs.jafc.5c01415

PubMed

40838659

More information

Latest update

10/8/2025