Metabolomics profiles of premenopausal women are different based on O-desmethylangolensin metabotype

Abstract

Urinary O-desmethylangolensin (ODMA) concentrations provide a functional gut microbiome marker of dietary isoflavone daidzein metabolism to ODMA. Individuals who do not have gut microbial environments that produce ODMA have less favourable cardiometabolic and cancer risk profiles. Urinary metabolomics profiles were evaluated in relation to ODMA metabotypes within and between individuals over time. Secondary analysis of data was conducted from the BEAN2 trial, which was a cross-over study of premenopausal women consuming 6 months on a high and a low soya diet, each separated by a 1-month washout period. In all of the 672 samples in the study, sixty-six of the eighty-four women had the same ODMA metabotype at seven or all eight time points. Two or four urine samples per woman were selected based on temporal metabotypes in order to compare within and across individuals. Metabolomics assays for primary metabolism and biogenic amines were conducted in sixty urine samples from twenty women. Partial least-squares discriminant analysis was used to compare metabolomics profiles. For the same ODMA metabotype across different time points, no profile differences were detected. For changes in metabotype within individuals and across individuals with different metabotypes, distinct metabolomes emerged. Influential metabolites (variables importance in projection score > 2) included several phenolic compounds, carnitine and derivatives, fatty acid and amino acid metabolites and some medications. Based on the distinct metabolomes of producers v. non-producers, the ODMA metabotype may be a marker of gut microbiome functionality broadly involved in nutrient and bioactive metabolism and should be evaluated for relevance to precision nutrition initiatives.

Keywords: Equol; Isoflavones; Metabolomics; Microbiome; O-desmethylangolensin.

Figure 1.. Urine sample selection among participants in a two-year soy intervention study. Two or four urine samples were selected from 20 women based on ODMA phenotype expression in eight urine samples over time.

Selection of samples for inclusion in metabolomics analysis and data analysis.

Figure 2.

First two components from partial least squares discriminant analysis (PLS-DA) comparing primary metabolism and biogenic amines untargeted metabolomics profiles in paired (within individual) comparisons across same ODMA phenotype (1); paired comparisons across different phenotypes (2); and, unpaired (across individuals) comparisons of ODMA non-producer and ODMA producer phenotypes.