Butyrate Alleviates Hyperuricemia by Selectively Targeting the Metronidazole/Neomycin-Sensitive Bacterium Dubosiella newyorkensis

Hyperuricemia (HUA), a metabolic disorder resulting from disrupted uric acid (UA) homeostasis, is the principal etiological factor for gout. This study investigated the therapeutic potential of gut microbiota modulation in HUA using antibiotic-treated mouse models with butyrate intervention. Selective antibiotic screening identified the Dubosiella-type strain Dubosiella newyorkensis (Dn) as an effective intervention for HUA. Dn treatment significantly reduced UA production, improved renal function markers, and decreased oxidative stress. Dn enriches Bacteroides and Romboutsia while suppressing the pathobiont Thomasclavelia, thereby enhancing the production of acetate, propionate, and butyrate. Molecular analyses demonstrated that Dn downregulated the expression of URAT1 while upregulating ABCG2, thereby promoting UA excretion. Histopathological evaluation confirmed that Dn restored the glomerular atrophy, tubular dilation, and collagen deposition induced by HUA. These findings suggest that Dn is a promising multitarget therapeutic agent for HUA and provides a scientific foundation for the development of novel microbiome-based strategies against HUA.