Uric acid (UA) is formed from the oxidation of hypoxanthine and xanthine catalyzed by xanthine oxidase (XOD), of which two-thirds is excreted by the kidney, while one-third passes via the intestine [1]. In recent years, studies have demonstrated that hyperuricemia (HUA) is a condition characterized by an excess of UA in vivo caused by a malfunction in purine metabolism [2]. According to the Gout Report White Paper (2021), the overall incidence of HUA in China has reached 13.3% to date, representing a population of approximately 177 million. More worryingly, as a major risk factor for diseases such as gout, chronic kidney diseases [3], cardiovascular diseases [4], and type 2 diabetes [5], HUA has imposed a significant burden on public health. Nowadays, there are two classes of drugs commonly employed for HUA treatment, which includes UA production inhibitors such as allopurinol and UA excretion promoters such as febuxostat. However, it is worth noting that these drugs are associated with serious adverse effects, such as hypersensitivity reactions and skin rashes, which restrict their clinical application [1,6]. Overall, it is vital to seek a safe and effective treatment for HUA.

For millennia, herbal medicine has been utilized in China for the prevention and treatment of various diseases, and is generally considered harmless and natural. Clerodendranthus spicatus (Thunb.) C. Y. Wu, known as kidney tea (KT) in Chinese Medicine (CM), is one of the four ethnomedicines in China. KT has been traditionally utilized to treat gout and urinary tract diseases for thousands of years as evidenced by historical medical literature named ‘Dang Ha Ya Long’ (7 AD) in the Dai nationality. Furthermore, its prescription named ‘Daiyao Qingfeng Granules’, which was used to lower UA, was also documented in this book [7]. Moreover, contemporary pharmacological studies have demonstrated the therapeutic and prophylactic effects of KT on gout and nephrolithiasis [[8], [9], [10]]. Elevated serum UA level resulted in the deposition of urate crystals in the joints, which indicated that HUA was the most vital risk factor for the development of gout [1]. Therefore, the pharmaceutical effect of KT on gout and kidney diseases may be attributed to its UA-lowering ability. In general, KT has diuretic, antioxidant and anti-inflammatory effects, which coincide with its main active substances, such as flavonoids, phenolic acids, terpenoids and volatile oils [11,12]. However, the mechanism by which KT lowers UA is still unclear.

Evidence suggests that the gut microbiota is approximately 10 times greater than the number of cells in the host body and is essential for host health by contributing to metabolism and immunological control [13,14]. More importantly, an increasing number of studies have supported a strong correlation between an imbalance in the intestinal flora and the development of HUA [15] and gout [16,17]. Furthermore, regulation of the gut microbiota and thus improvement in HUA can be achieved by administration of probiotics to hosts such as Lactobacillus [18] and Limosilactobacillus fermentum [19], which in a deeper sense indicates that the intestinal flora may well be a new strategy for the treatment of HUA. On the other hand, disruptions in the intestinal microecology may yield perturbations in host-microbiota co-metabolites, exacerbating dysregulation of host metabolic pathways. Fortunately, phenolic acids such as rosmarinic acid and ursolic acid, the main bioactive chemicals of KT, were proven to modulate the composition of the intestinal flora and to alter the abundance of specific bacteria, ultimately ameliorating the disease status of the host [[20], [21], [22]]. Furthermore, metabolic disorders have been implicated in the pathogenesis of HUA, and numerous studies have indicated that herbal medicine alleviates HUA by modulating the host metabolic profile [23,24]. It is reported that amino acid, lipid and carbohydrate metabolism perturbations have been observed in HUA patients [25]. However, whether KT improves HUA by regulating the intestinal flora and metabolites warrants further investigation.

In this study,16S rRNA gene sequencing was conducted to illustrate the effects of KT on the intestinal flora and untargeted metabolomics was used to analyze the metabolites in feces and serum. In addition, the correlation between the differential gut microbiota and metabolites induced by KT were analyzed. This research aims to elucidate the mechanism of KT in treating HUA and to lay the theoretical foundation for the future application of KT in lowering UA.