Sulforaphane-driven reprogramming of gut microbiome and metabolome ameliorates the progression of hyperuricemia

Abstract

Introduction: Currently, revealing how to prevent and control hyperuricemia has become an essential public health issue. Sulforaphane has a wide range of applications in the management of hyperuricemia. Objective: The study objective was to verify the uric acid-lowering effects and the regulation of the gut-kidney axis mediated by sulforaphane and identify host-microbial co-metabolites in hyperuricemia. Methods: A hyperuricemia model was established by administering feedstuffs with 4% potassium oxonate and 20% yeast. Forty male Sprague–Dawley rats were randomly divided into the normal control, hyperuricemia, allopurinol, and sulforaphane groups. Animals were treated by oral gavage for six consecutive weeks, and then phenotypic parameters, metabolomic profiling, and metagenomic sequencing were performed. Results: Sulforaphane could lower uric acid by decreasing urate synthesis and increasing renal urate excretion in hyperuricemic rats (P＜0.05). We identified succinic acid and oxoglutaric acid as critical host-gut microbiome co-metabolites. Moreover, sulforaphane improved the diversity of microbial ecosystems and functions, as well as metabolic control of the kidney. Notably, sulforaphane exerted its renoprotective effect through epigenetic modification of Nrf2 and interaction between gut microbiota and epigenetic modification in hyperuricemic rats. Conclusion: We revealed that sulforaphane could ameliorate the progression of hyperuricemia by reprogramming the gut microbiome and metabolome. Our findings may provide a good means for efficiently preventing and treating hyperuricemia.

Keywords

• Hyperuricemia
• Sulforaphane
• Gut microbiota
• Host-gut microbiome co-metabolite