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Gut microbiota and uric acid excretion signaling in pathogenesis of hyperuricemia and acute gouty arthritis

Year: 2026

Type: article

Abstract: Hyperuricemia (HUA) and acute gouty arthritis (AGA) represent distinct pathological stages of gout, with the intestine playing a critical role in uric acid (UA) excretion. By establishing HUA and AGA mouse models, we observed both induced renal and intestinal pathology, elevated inflammatory factors, reduced expression of barrier proteins (Occludin, Claudin-1, and Zonula occludens-1 [ZO-1]), increased permeability markers (DAO and D-LA), upregulation of GLUT9, downregulation of ABCG2, and more severe pathology in AGA. 16S rRNA sequencing revealed alterations in gut microbial composition, with 11 bacterial genera overlapping between the 2, including g_[Eubacterium]_siraeum_group , g_Harryflintia , g_Ruminococcus , etc. Application of gut microbiota from two models to intestinal epithelial cells (IECs) confirmed that these microbiota exacerbated damage in HUA/NCM460 and AGA/NCM460 cells. RNA sequencing identified the ErbB3/PI3K/AKT pathway as significantly activated in HUA, and the ADRB2/cAMP/PKA/CREB pathway in AGA, which were further validated in vivo . This study identifies specific gut microbiota in HUA/AGA and elucidates core pathways involved in pathogenesis, providing new insights into gut-targeted management strategies.

Source: iScience

DOI: 10.1016/j.isci.2026.117072