Efficacy and mechanisms of compound Bai Mao Yin in regulating uric acid transport and improving the intestinal microbiota to alleviate hyperuricemia via the enterorenal axis.

BACKGROUND

The compound Bai Mao Yin (BMY) has demonstrated therapeutic efficacy in reducing uric acid (UA) levels; however, its underlying mechanisms remain unclear.

METHODS

The UA-lowering effects of BMY were evaluated in a cohort of 40 patients with hyperuricemia (HUA) who received BMY treatment for 90 days. Fecal samples were collected at baseline (day 0), mid-treatment (day 30), and post-treatment (day 90) for metagenomic sequencing to analyze changes in gut microbiota and identify potential BMY targets in HUA. These clinical findings were validated in a hyperuricemic mouse model induced by xanthine and potassium oxonate. Mouse fecal samples were analyzed via 16S rDNA (V3-V4 region) sequencing to assess microbiota shifts. Additionally, fecal microbiota transplantation (FMT) from BMY-treated mice to HUA mice and in vitro cell experiments using HK2 cells were conducted to investigate the roles of BMY and the reconstructed microbiota in UA metabolism, renal UA transport, and inflammation through upstream signaling pathways.

RESULTS

Clinical cohort studies demonstrated that the BMY effectively lowers UA levels in patients with HUA without inducing hepatorenal toxicity. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of metagenomic data revealed that BMY modulates the gut microbiota and influences ATP-binding cassette transporters and UA metabolism-related pathways. In animal models, BMY increased the relative abundance of beneficial gut bacteria, reduced intestinal permeability, and regulated UA transporters in both intestinal and renal systems, contributing to UA reduction. In vitro assays showed that BMY directly decreased UA levels in the cell supernatant and suppressed interleukin-1β (IL-1β) and interleukin-6 (IL-6) expression by downregulating the TLR4/MYD88/NFκB signaling pathway, thereby alleviating inflammation.

CONCLUSIONS

Compound BMY was found to improve the intestinal microenvironment and modulate UA transport via the enterorenal axis, effectively reducing HUA.