Quercetin's antitumor effect in bladder cancer: Synergistic regulation of gut microbiota and l-serine metabolic pathway

Quercetin is a bioflavonoid that is abundant and easy to extract, and has beneficial effects such as anti-cancer, anti-inflammatory, and antioxidant properties. We have demonstrated that oral administration of quercetin in an animal model inhibits bladder cancer (BCa), with inhibition rates of 48.5% (100 mg/kg) and 51.41% (200 mg/kg), respectively. Additionally, quercetin treatment reverses gut microbiota dysbiosis in the model mice. Metabolomics results showed that l -serine had the highest correlation coefficient with tumor weight in model mice ( r = 0.935), and oral quercetin reduced l -serine levels by modulating the abundance of Escherichia-Shigella in the gut microbiota. Transcriptomic sequencing results revealed that quercetin treatment downregulates the expression of phosphoserine phosphatase (PSPH), inhibiting the serine synthesis pathway (SSP) and reducing l -serine levels in the body, thus exerting anti-tumor effects. Fecal microbiota transplantation (FMT) experiments reproduced the pharmacological results of oral quercetin treatment for BCa and identified Escherichia coli Nissle 1917 as capable of inhibiting BCa growth by metabolizing l -serine. In conclusion, quercetin effectively inhibits the progression of BCa by comprehensively regulating l -serine levels in the body at both endogenous and exogenous levels.