(PTFS14-03-26) Soy Isoflavone Metabotype Distinguishes Urine but Not Serum Metabolome in a Biobanked Cohort

Objectives: Daidzein, an isoflavone in soy, is metabolized to O-desmethylangolensin (ODMA) by select gut bacteria. ODMA production is not universal, resulting in an ODMA metabotype: producers and non-producers.  Given a documented association between non-producers and poorer cardiometabolic outcomes, biofluid metabolomics have been used to investigate this metabotype's influence on host metabolism of compounds.  The aim of this study was to evaluate the utility of biobanked urine and serum samples for metabolomics analysis by examining metabolite profiles across ODMA producers and non-producers.

Methods: Samples from the Study of Women's Health Across the Nation, a study of women aged 42-52, were used.  Urine and serum metabolites were measured via HPLC-MS/MS, and urinary ODMA and daidzein classified metabotypes: ODMA/daidzein=0, non-producers; ODMA/daidzein >0 but less than 0.5, low-producers; and ODMA/daidzein >0.5, high-producers.  MS-DIAL was used for peak alignment and processing.  Sparse canonical correlation analysis of urine and serum was conducted in R, and metabolome differences were compared using PCA and PLS-DA in Metaboanalyst.

Results: Sparse canonical correlation analysis revealed a high correlation between metabolites in urine and serum (r_c=0.7909; p=0.001).  When biofluids were examined separately, PCA and PLS-DA analyses demonstrated inconsistencies.  PCA revealed a significant difference in urine metabolite profiles between metabotypes (R²=0.049, p=0.023), but this was not evident in serum.  Urine samples exhibited some clustering in PLS-DA (Q²=0.45), but serum samples showed minimal segregation (Q² < 0).

Conclusions: In this sample of SWAN participants, metabolomics analyses revealed ODMA metabotype groups have some significantly different metabolite clusters in urine, but separation was not as apparent in serum.  When utilizing metabolomics to examine nutritional relationships, this study affirmed the significance of aligning biobanked sampling methods to the fundamental objective(s).

Funding Sources: George Mason University, College of Public Health pilot funding
Supported by the Food and Human Health program from the USDA National Institute of Food and Agriculture