<i>Paecilomyces cicadae</i> ‐fermented <i>Radix astragali</i> modulates short‐chain fatty acids metabolism in the intestine through gut microbiota and ameliorates hyperuricaemia

BACKGROUND AND PURPOSE: Hyperuricaemia, a severe metabolic disorder linked to gout, is increasingly prevalent worldwide. Radix astragali, as a drug-food homologous material, has significantly expanded the market for novel functional foods. The solid-state fermentation products of R. astragali and Paecilomyces cicadae (RPF) promise to be candidates for lowering uric acid. Here, we have investigated the effects of RPF, using a model of hyperuricaemia in rats. EXPERIMENTAL APPROACH: Hyperuricaemia, and damage to liver and kidney, was induced in male Sprague-Dawley rats receiving a high purine diet. Gut microbiota and short-chain fatty acid metabolism were examined by multi-omics analysis of rat faeces. Faecal microbiota transplantation was used to assess the therapeutic potential of gut microbiota and RPF. Effects of Eubacterium siraeum on uric acid and short-chain fatty acid metabolism were examined, in vitro and in hyperuricaemic rats. KEY RESULTS: RPF regulated dysbiosis of gut microbiota and restored the relative abundance of Ruminococcus and Eubacterium, which was associated with normalisation of serum levels of uric acid and short chain fatty acids. In vitro, the E. siraeum DSM15702 strain extensively degraded uric acid. In vivo data from probiotic-treated, hyperuricaemic rats, indicated a reduction of circulating uric acid levels. CONCLUSION AND IMPLICATIONS: Our study suggests that the gut microbiota-short chain fatty acid axis may play a crucial role in maintaining intestinal homeostasis and in modulating the excretion of uric acid. E. siraeum may serve as a potential adjunct therapy for management of hyperuricaemia.