Gut microbiome dysbiosis accelerates osteoarthritis progression by inducing IFP-SM inflammation in “double-hit” mice

作者：Su Liu, Huihui Xu, Liu L, Wenjing Ma, Hao Fan, Fei Liu, Zhi Wei, Jing Hao, Zhifa Zheng, Lina Zhao, Bo Yang, Zhihong Wu · 发表于：Arthritis Research & Therapy · 年份：2025 · DOI：10.1186/s13075-025-03602-y · 被引用次数：15 · 研究领域：Gut microbiota and health、Oral microbiology and periodontitis research、Osteoarthritis Treatment and Mechanisms

BACKGROUND: This study investigates the complex interplay between gut microbiome dysbiosis and systemic inflammation as a critical risk factor in the pathogenesis of osteoarthritis (OA). Furthermore, it elucidates the role of gut microbiota (GMB) dysbiosis in driving OA progression. METHODS: A refined "double-hit" murine model was developed to explore this relationship. The first intervention involved inducing gut microbiota dysbiosis through the administration of colistin and Escherichia coli, followed by surgical destabilization of the medial meniscus (DMM) to induce joint instability. The composition of the gut microbiota was analyzed using 16 S rRNA sequencing. Gut permeability was assessed via RT-PCR and immunofluorescence (IF), while mRNA sequencing was employed to examine alterations in gene expression. RESULTS: Treatment with colistin and E. coli significantly altered the gut microbiota composition, characterized by a marked increase in the absolute abundance of Firmicutes and a concomitant reduction in Bacteroidota and the Bacteroidota/Firmicutes (B/F) ratio. At the genus level, the absolute abundances of Muribaculaceae, Rikenellaceae_RC9_gut_group, and Roseburia were significantly diminished. GMB dysbiosis led to the downregulation of intestinal tight junction proteins, including ZO-1 and Occludin, resulting in increased intestinal permeability. Consequently, serum levels of lipopolysaccharide (LPS) were significantly elevated, indicating LPS translocation from the ...