(PTFS03-05-25) Supplementation of Equol Producing Bacteria Alters Sex Steroid Homeostasis in a Sexual Dimorphic Manner

Objectives: Equol is an intestinal microbial metabolite derived from the soy isoflavone daidzein, known for its high estrogenic capacity and anti-inflammatory properties. These attributes are considered beneficial for postmenopausal women with estrogen deficiency; however, the impact of intestinal equol-producing capacity on sex steroid homeostasis in men and premenopausal women remains unclear. Interestingly, fewer than half of the human population harbor intestinal microbiota capable of producing equol, which may result in a dichotomy in the effects of soy consumption on sex steroids. We sought to investigate the impact of intestinal equol-producing capacity on sex steroid homeostasis using a gnotobiotic mouse model.

Methods: We have identified two human microbial communities that are non-equol-producers (Microbiota A and B). These microbiotas were used to inoculate male and female germ-free mice through fecal microbiota transplantation (FMT). Half of the mice were supplemented with a cocktail of four equol-producing bacteria (EQ), namely Bifidobacterium breve, Slackia equolifaciens, Slackia isoflavoniconvertens, and Adlercreutzia equolifaciens, resulting in a 2x2 factorial design within each sex. Mice were fed a natural ingredient diet that contains soy isoflavones. Five weeks after FMT, mice were euthanized and the weight of uteri, testes, and fat pads, as well as gonadal sex steroids were determined.

Results: In both sexes, Microbiota B-colonized mice had significantly lower gonadal steroid levels than Microbiota A. A sexual dimorphic phenomenon was discovered whereby EQ supplementation led to sex steroid differences only in Microbiota B-colonized males and Microbiota A-colonized females. Specifically, Microbiota B+EQ males had significantly lower testicular testosterone, dihydrotestosterone, and gonadal fat mass compared to those without supplementation. Microbiota A+EQ females had significantly lower ovarian estradiol level compared to those without supplementation.

Conclusions: Equol-producing capacity may differentially impact sex steroid production in male vs. females based on the commensal microbiota. Our data also demonstrate that the intestinal microbiota has a strong impact on sex steroid production.

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