16S rRNA and Metagenomics Combined with UPLC-Q/TOF-MS Metabolomics Analysis Reveals the Potential Mechanism of Radix Astragali Against Hyperuricemia in Mice

Song Deng,1,* Kaiwei Cai,1,* Chaoying Pei,1 Xingyuan Zhang,1 Xiaoyi Xiao,1 Ye Chen,1 Ying Chen,1 Rongyao Liang,1 Yanlong Chen,1 Pei Li,1 Zhiyong Xie,2 Qiongfeng Liao1 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiongfeng Liao, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China, Tel/Fax +86 02039358081, Email zyfxliao@gzucm.edu.cn Zhiyong Xie, School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, 510006, People’s Republic of China, Tel/Fax +86 075523260207, Email xiezhy@mail.sysu.edu.cnPurpose: This study aimed to investigate the underlying treatment mechanism of Radix Astragali (RA) in hyperuricemia from the perspective of microbiota and metabolomics.Methods: We used potassium oxyazinate (PO) to induce hyperuricemia mice, and we determined serum alanine aminotransferase/aspartate aminotransferase (ALT/AST), xanthine oxidase (XOD), creatinine (CRE), uric acid (UA), blood urea nitrogen (BUN) levels, liver XOD levels and assessed the kidney tissue histopathology. The therapeutic mechanism of RA in hyperuricemic mice was studied by 16S rRNA, metagenomic sequencing and metabolomics.Results: Our research showed that RA has therapeutic effect in hyperuricemia mice, such as slow the weight loss, repair kidney damage, and downregulate serum UA, XOD, CRE, ALT/AST, BUN, and liver XOD levels. RA restored the disturbance structure of the microbiota in hyperuricemia mice by increasing the relative abundances of beneficial bacteria (Lactobacillaceae and Lactobacillus murine) but decreasing the relative abundances of pathogenic bacteria (Prevotellaceae, Rikenellaceae and Bacteroidaceae). Meanwhile, we found that RA directly regulated the metabolic pathway (such as linoleic acid metabolism and glycerophospholipid metabolism) and indirectly regulated bile acid metabolism by mediating microbiota to ameliorate metabolic disorders. Subsequently, there was a robust correlation between specific microbiota, metabolites and the disease index.Conclusion: The ability of RA to protect mice against hyperuricemia is strongly linked to the microbiome-metabolite axis, which would provide evidence for RA as a medicine to prevent or treat hyperuricemia.Graphical Abstract: Keywords: Radix Astragali, hyperuricemia, microbiota, metabolism, bile acid