Metabolomics reveals differences between three daidzein metabolizing phenotypes in adults with cardiometabolic risk factors

• Published in: Molecular nutrition & food research 2017-01, Vol.61 (1), p.np-n/a
• Main Authors: Reverri, Elizabeth J., Slupsky, Carolyn M., Mishchuk, Darya O., Steinberg, Francene M.
• Format: Article
• Language: English
• Subjects: Adults; Alanine; Asparagine; Cardiometabolic risk; Cytokines; Daidzein; Equol - metabolism; Excretion; Female; Food; Glycine max; Health risks; Humans; Inactivation, Metabolic; Inflammation; Intestinal microflora; Isoflavones; Isoflavones - metabolism; Isoflavones - pharmacokinetics; Ketoglutaric acid; Male; Metabolic Syndrome - metabolism; Metabolism; Metabolites; Metabolomics; Metabolomics - methods; Methionine; Microorganisms; Middle Aged; Nuts; Phenotype; Risk analysis; Risk Factors; Soy; Soy products; Trimethylamine; Urine
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201600132

Scope The soy isoflavone, daidzein, is metabolized by gut microbiota to O‐desmethylangolensin (ODMA) and/or equol. Producing equol is postulated as a contributing factor for the beneficial effects of soy. Methods and results This randomized, controlled, cross‐over design used an untargeted metabolomic approach to assess the metabolic profile of different daidzein metabolizers. Adults (n = 17) with cardiometabolic risk factors received soy nuts or control food for 4 weeks, separated by a 2‐week washout. No significant differences were detected pre‐ and postintervention and between interventions. Examination of the ability to metabolize daidzein revealed three groups: ODMA only producers (n = 4), equol + ODMA producers (n = 8), and nonproducers (n = 5). Analysis of the serum metabolome revealed nonproducers could be distinguished from ODMA‐only and equol + ODMA producers. Differences between these phenotypes were related to obesity and metabolic risk (methionine, asparagine, and trimethylamine) with equol + ODMA producers having lower concentrations, yet paradoxically higher pro‐inflammatory cytokines. In urine, nonproducers clustered with ODMA producers and were distinct from equol + ODMA producers. Urinary metabolite profiles revealed significantly higher excretion of fumarate and 2‐oxoglutarate, as well as pyroglutamate, alanine, and the gut microbial metabolite dimethylamine in equol + ODMA producers. Conclusion These results emphasize that the serum and urine metabolomes are distinct based on the ability to metabolize isoflavones. Soy consumption is associated with beneficial health effects, yet individual responsiveness is variable. Untargeted metabolomics were used to examine the metabolic profile (composite of biochemical markers, intermediary metabolism and secondary metabolites influenced by gut microbiota) of different daidzein metabolizers. Three distinct phenotypes were observed that were correlated with O‐desmethylangolensin (ODMA) only producers, equol + ODMA producers, and nonproducers. Results emphasize that serum endogenous metabolomes are distinct based on the ability to metabolize soy isoflavones.