Stability of equol production capability is associated with the diversity of the gut microbiota of the host: a prospective cohort study

Equol, a gut microbiota–derived metabolite of the soy isoflavone daidzein that acts mainly via estrogen receptor β, has been linked to several health benefits, including relief of menopausal symptoms and prevention of arteriosclerosis. However, little is known about how equol production capability changes over time and how these changes relate to the gut microbiota. We analyzed data from 498 community-dwelling adults who participated annually in a health checkup between 2016 and 2019. Equol production was assessed each year using urinary equol and daidzein concentrations. Participants were classified as producers when log10(equol/daidzein) > − 1.75 and were further categorized as stable producers (equol positive in all 4 years), unstable producers (equol positive in at least 1 but not all years), or non-producers (equol negative in all years). Gut microbiota profiles were obtained from fecal samples collected in 2016 and analyzed for bacterial diversity, composition, and predicted metabolic pathways. Dietary daidzein intake was estimated using a validated brief-type self-administered diet history questionnaire. Of the 498 participants, 30.9% were stable producers, 26.1% unstable producers, and 43.0% non-producers. Stable producers showed significantly higher gut bacterial diversity than unstable producers and non-producers and a distinct microbiota composition, despite comparable daidzein intake across groups. At the genus level, differential abundance analysis indicated that taxa such as Eubacterium coprostanoligenes group, Subdoligranulum, Ruminococcus, Alistipes, and Coprococcus were enriched in stable producers, whereas Ruminococcus gnavus group, Fusobacterium, Eggerthella, Flavonifractor, and Bacteroides were more abundant in non-producers. Several genera enriched in stable producers are known short-chain fatty acid producers, whereas some genera enriched in non-producers have been reported in the context of intestinal dysbiosis and inflammation. Functional prediction analysis further indicated that stable producers had microbiota with enhanced pathways related to vitamin B and menaquinone biosynthesis, sulfate degradation, and methanogenesis. The stability of equol production capability over time is associated with higher gut microbiota diversity and specific compositional and functional features. A gut microbiota composition favoring saccharolytic and butyrogenic bacteria may support sustained equol production, whereas a microbiota dominated by potentially pro-inflammatory taxa may be less conducive to equol production.