Microbial metabolites are associated with a high adherence to a Mediterranean dietary pattern using a 1H-NMR-based untargeted metabolomics approach

J Nutr Biochem. 2017 Oct:48:36-43. doi: 10.1016/j.jnutbio.2017.06.001. Epub 2017 Jun 7.


The study of biomarkers of dietary patterns including the Mediterranean diet (MedDiet) is scarce and could improve the assessment of these patterns. Moreover, it could provide a better understanding of health benefits of dietary patterns in nutritional epidemiology. We aimed to determine a robust and accurate biomarker associated with a high adherence to a MedDiet pattern that included dietary assessment and its biological effect. In this cross-sectional study, we included 56 and 63 individuals with high (H-MDA) and low (L-MDA) MedDiet adherence categories, respectively, all from the Prevención con Dieta Mediterránea trial. A 1H-NMR-based untargeted metabolomics approach was applied to urine samples. Multivariate statistical analyses were conducted to determine the metabolite differences between groups. A stepwise logistic regression and receiver operating characteristic curves were used to build and evaluate the prediction model for H-MDA. Thirty-four metabolites were identified as discriminant between H-MDA and L-MDA. The fingerprint associated with H-MDA included higher excretion of proline betaine and phenylacetylglutamine, among others, and decreased amounts of metabolites related to glucose metabolism. Three microbial metabolites - phenylacetylglutamine, p-cresol and 4-hydroxyphenylacetate - were included in the prediction model of H-MDA (95% specificity, 95% sensitivity and 97% area under the curve). The model composed of microbial metabolites was the biomarker that defined high adherence to a Mediterranean dietary pattern. The overall metabolite profiling identified reflects the metabolic modulation produced by H-MDA. The proposed biomarker may be a better tool for assessing and aiding nutritional epidemiology in future associations between H-MDA and the prevention or amelioration of chronic diseases.

Keywords: Biomarkers; Dietary patterns; High adherence; Mediterranean diet; Metabolomics; Microbiota.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / urine*
  • Cresols / urine
  • Cross-Sectional Studies
  • Diet, Mediterranean*
  • Female
  • Gastrointestinal Microbiome / physiology*
  • Glutamine / analogs & derivatives
  • Glutamine / urine
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Metabolomics / methods
  • Middle Aged
  • Phenylacetates / urine
  • ROC Curve


  • Biomarkers
  • Cresols
  • Phenylacetates
  • Glutamine
  • 4-cresol
  • 4-hydroxyphenylacetate
  • phenylacetylglutamine