(P20-013-23) Sexual Dimorphic Metabolism of Soy Isoflavone Daidzein: Potential Implication in Precision Nutrition

Objectives: Equol is a gut microbial metabolite derived from soy isoflavone daidzein that has high estrogenic potency and antioxidant properties. Less than half of the human population can produce equol, while equol-producing capacity is thought to be a critical determinant in obtaining the health benefits of soy. Interestingly, it has been reported that women are more likely to become equol-producers after chronic soy consumption compared to men. Women are also thought to produce a higher concentration of equol than men. However, the sex differences of equol production are not consistently observed among clinical trials, likely due to inherent confounding variables in humans such as gut microbiome and host genetics. Therefore, we sought to assess sexual dimorphism in equol production using a controlled model system by colonizing germ-free mice with human microbiomes. In this study, we aim to test the hypothesis that females are more likely to harbor equol-producing bacteria and exert greater equol-producing capacity than males.

Methods: Six- to nine-week-old male and female germ-free mice were colonized through fecal microbial transplantation with feces collected from one of the ten human donors. Mice were fed a semi-purified diet containing 1.5% (wt/wt) daidzein. Two weeks after colonization, serum was collected to determine equol-producing capacity. Cecal microbiota was characterized using 16S rRNA gene sequencing.

Results: Among the ten human microbial communities, two of them consistently induced equol-producing phenotypes in recipient mice of both sexes. Interestingly, one fecal sample exerts equol-producing phenotypes in female recipients but not males. Within each equol-producing microbial community, female recipient mice had significantly greater serum equol concentration and lower daidzein compared to males.

Conclusions: Our data demonstrated a sexual dimorphic phenomenon that female mice are more likely to retain equol-producing bacteria and produce a greater level of equol than males when inoculated with the same donor feces. Further understanding of factors that contribute to these sex-specific differences may inform precision nutrition when developing next-generation probiotics to maximize health benefits from soy consumption.

Funding Sources: Agricultural Science and Extension for Economic Development, Purdue University