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

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.