Abstract:[Objective]To study the regulatory effect of (S)-equol on human gut microbiota and the metabolic effect of human gut microbiota on (S)-equol.[Methods] The interaction between (S)-equol and human gut microbiota was detected by batch fermentation in vitro,bacterial 16S rRNA gene high-throughput sequencing,gas chromatography,high performance liquid chromatography (HPLC),and mass spectrometry.[Results](S)-equol had no significant effect on the overall structure of human gut microbiota or the concentrations of short chain fatty acids (SCFAs).No significant change in the relative abundance of bacteria was detected between the 0.45 mmol/L (S)-equol group and the control group.However,0.90 mmol/L (S)-equol significantly increased the relative abundance of conditional pathogens such as Enterobacteriaceae and reduced that of potential probiotics Coprococcus.The concentration of (S)-equol in the fermentation broth decreased by 15%-30%,which suggested that (S)-equol may be degraded or modified by gut microbiota.[Conclusion] From the perspective of regulating gut microbiota in vitro,0.45 mmol/L (S)-equol is safe,while 0.90 mmol/L (S)-equol may disturb the balance of gut microbiota.(S)-equol can be further metabolized by human gut microbiota,and the structure and function of the specific metabolites and the biological safety of (S)-equol in vivo remain to be studied.