Maximizing the Estrogenic Potential of Soy Isoflavones through the Gut Microbiome: Implication for Cardiometabolic Health in Postmenopausal Women

Soy isoflavones have been suggested as an alternative treatment for managing postmenopausal symptoms and promoting long-term health due to their structural similarity to mammalian estrogen and ability to bind to estrogen receptors. Among all soy isoflavones and their metabolites, (S)-equol is known for having the strongest estrogenic activity. Equol is a metabolite of the soy isoflavone daidzein produced through intestinal bacterial metabolism. However, more than half of the human population is not able to produce equol due to the lack of equol-producing bacteria in their gastrointestinal tract. The interpersonal variations in the gut microbiome complicate the interpretation of data collected from humans. Furthermore, because rodents are efficient equol-producers, translatability between rodent models and humans is challenging. Herein, we first summarized the current knowledge of the microbial conversion of daidzein to equol, its relation to health, and proposed the need for developing model systems by which equol production can be manipulated while controlling other known confounding factors. Determining the necessity of equol-producing capacity within a gut microbial community when consuming soy as a functional ingredient, and identifying strategies to maximize equol production by modulating the gut microbiome, may provide future therapeutic approaches to improve the health of postmenopausal women.

Automated summary

Soy isoflavones, particularly (S)-equol, have been proposed as an alternative treatment for managing postmenopausal symptoms and improving long-term health. However, the lack of equol-producing bacteria in the gastrointestinal tract of over half of the human population complicates the interpretation of data collected from humans. Rodent models, which efficiently produce equol, also pose challenges in translating findings to humans. The development of model systems to manipulate equol production and control confounding factors is needed to determine the therapeutic approaches for maximizing equol production and improving the health of postmenopausal women consuming soy.