Limosilactobacillus reuteri prevents progression of ankylosing spondylitis in mice by restoring gut microbiota-metabolism homeostasis

作者：Lianjun Yang, Ke You, Kun Wang, Bin Liu, Tao Chen, Zhifei Cui, Dawei Zhang, Zhihai Su, Xiang Liu, Hai Lü · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06681-2 · 被引用次数：4 · 研究领域：Spondyloarthritis Studies and Treatments、Gut microbiota and health、Rheumatoid Arthritis Research and Therapies

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by progressive spinal fusion and systemic inflammation. Recent studies suggest that gut microbiota plays a crucial role in the pathogenesis of AS. METHODS: This study investigated the therapeutic effects of Limosilactobacillus reuteri (L. reuteri) on AS progression and its underlying mechanisms using a proteoglycan (PG)-induced mouse model. Female BALB/c mice (n = 10/group) were randomized into control group, PG group and PG + L. reuteri group. Disease severity was assessed via arthritis scores, Micro-CT images, and histopathology. Serum cytokines (IL-1β, IL-18, IL-17A, IL-23) were measured by ELISA. Intestinal barrier integrity was evaluated using FITC-dextran permeability, immunofluorescence (ZO-1, occludin), and colon histology. Gut microbiota (16S rRNA sequencing) and fecal metabolites (untargeted metabolomics) were analyzed. AhR/NLRP3 pathway activity was assessed via qRT-PCR (AhR, CYP1A1, CYP1B1, and NLRP3). RESULTS: Our findings demonstrated that L. reuteri significantly alleviated AS progression, as evidenced by reduced joint swelling and erythema, alongside a decreased arthritis index and paw thickness. Furthermore, treatment with L. reuteri resulted in a marked reduction in serum levels of pro-inflammatory cytokines, including IL-1β, IL-18, IL-17A, and IL-23, indicating its potential to modulate systemic inflammation. Additionally, L. reuteri enhanced intestinal mucosal barrier f...