Daidzein at 40 mg/kg attenuated DSS-induced colitis in mice by enriching β-glucuronidase-producing gut bacteria (especially Bacteroides thetaiotaomicron), with effects linked to host ERβ signaling, suppression of PI3K/Akt/mTOR, and restored autophagy, suggesting a potential Microbiota-GUS-ERβ-PI3K/Akt/mTOR-autophagy axis.
Administration of 40 mg/kg daidzein significantly attenuated DSS-induced colitis in mice.
Daidzein reprogrammed the gut microbiota composition, enriching β-glucuronidase (GUS)-producing bacteria, especially Bacteroides thetaiotaomicron.
The effects of microbially bioactivated daidzein were associated with host estrogen receptor beta (nβ) signaling.
Pharmacological blockade of ERβ supported the involvement of ERβ signaling in suppressing PI3K/Akt/mTOR signaling and restoring autophagy, contributing to intestinal epithelial repair.
The authors propose a Microbiota-GUS-ERβ-PI3K/Akt/mTOR-autophagy mechanistic axis underlying daidzein's anticolitic effect.
This study in mice looked at how daidzein, a flavonoid found in soy, helps protect against colitis, a form of inflammatory bowel disease. When mice with chemically induced colitis were given daidzein at 40 mg/kg, their colitis was less severe: the gut lining stayed more intact and inflammation was lower. The researchers found that daidzein changed the mix of gut bacteria, increasing bacteria that make an enzyme called β-glucuronidase, especially Bacteroides thetaiotaomicron. This research suggests these bacteria help convert daidzein into a more active form. That active form appeared to act through a host receptor, estrogen receptor beta, which dampened a cell-growth signaling pathway (PI3K/Akt/mTOR) and restored autophagy, a cellular cleanup process that supports repair of the gut lining. Blocking the receptor with drugs supported this link. The work suggests that how well a dietary compound works may depend on a person's gut bacteria, which could eventually inform personalized nutrition approaches. However, the findings are from animal experiments, and the proposed pathway is described as potential, so they do not show that daidzein would work the same way in people with IBD.
Ding S, Chen Y, Li J, Liu G, He X, Fang J. (2026). Gut Microbiota-Derived β-Glucuronidase Governs the Anticolitic Efficacy of Daidzein via the ERβ-PI3K/Akt/mTOR-Autophagy Axis.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.6c08490