Association between lignan polyphenol bioavailability and enterotypes of isoflavone metabolism: A cross-sectional analysis

Lignan polyphenols derived from plants are metabolized by bacteria in the gut to mammalian lignans, such as enterolactone (ENL) and enterodiol (END). Mammalian lignan intake has been reported to be associated with obesity and low blood glucose levels. However, the factors that are responsible for individual differences in the metabolic capacity for ENL and END are not well understood. In the present study, the effects of enterotypes of isoflavone metabolism, equol producers (EQP) and O-desmethylangolensin producers (O-DMAP), on lignan metabolism were examined. EQP was defined by urinary daidzein (DAI) and equol concentrations as log(equol/DAI) ≥ –1.42. O-DMAP was defined by urinary DAI and O-DMA concentrations as O-DMA/DAI > 0.018. Isoflavone and lignan concentrations in urine samples from 440 Japanese women were measured by gas chromatography-mass spectrometry. Metabolic enterotypes were determined from the urinary equol and O-DMA concentrations. Urinary END and ENL concentrations were compared in four groups, combinations of EQP (+/–) and O-DMAP (+/–). The urinary lignan concentration was significantly higher in the O-DMAP/EQP group (ENL: P<0.001, END: P<0.001), and this association remained significant after adjusting for several background variables (END: β = 0.138, P = 0.00607 for EQP and β = 0.147, P = 0.00328 for O-DMAP; ENL: β = 0.312, P<0.001 for EQP and β = 0.210, P<0.001 for O-DMAP). The ENL/END ratio was also highest in the O-DMAP/EQP group, indicating that equol and O-DMA metabolizing gut bacteria may be involved in lignan metabolism. In conclusion, urinary lignan concentrations were significantly higher in groups containing either EQP or O-DMAP than in the non-EQP/non-O-DMAP group. The variables and participants in this study were limited, which the possibility of confounding by other variables cannot be ruled out. However, there are no established determinants of lignan metabolism to date. Further research is needed to determine what factors should be considered, and to examine in different settings to confirm the external validity.