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在胶原诱导性关节炎小鼠模型中研究肠道微生物群在类风湿关节炎发病机制及进展中的作用。

Investigating the Role of Gut Microbiota in the Pathogenesis and Progression of Rheumatoid Arthritis in a Collagen-Induced Arthritis Mouse Model.

作者信息

Belvončíková Paulína, Macáková Kristína, Tóthová Nikola, Babál Pavel, Tarabčáková Lenka, Gardlík Roman

机构信息

Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia.

Institute of Pathological Anatomy, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia.

出版信息

Int J Mol Sci. 2025 May 26;26(11):5099. doi: 10.3390/ijms26115099.

Abstract

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder whose precise etiology remains unclear, though growing evidence implicates gut microbiota in its pathogenesis. This study aimed to investigate the role of gut microbiota in the onset and progression of RA by employing fecal microbiota transplantation (FMT) in a collagen-induced arthritis (CIA) mouse model using DBA/1J and Aire/ strains. Mice received FMT from healthy donors, treatment-naïve RA patients, or treated RA patients in relapse, followed by assessment of microbiota composition via 16S rRNA sequencing, arthritis severity scoring, histological evaluations, and systemic inflammatory markers. The findings revealed distinct microbiota clustering patterns post-FMT across experimental groups, highlighting strain-specific colonization effects. Notably, genera such as Bifidobacterium and Paraprevotella correlated positively with arthritis severity in DBA/1J mice, whereas Corynebacterium, Enterorhabdus, and Odoribacter exhibited negative correlations, suggesting potential protective roles. Despite these microbial differences, minor variations in arthritis scores, paw inflammation, or systemic inflammation were observed among FMT groups. This indicates that although gut microbiota alterations are associated with RA pathogenesis, further investigation with larger cohorts and comprehensive sequencing approaches is essential to elucidate the therapeutic potential of microbiome modulation in autoimmune diseases.

摘要

类风湿性关节炎(RA)是一种慢性全身性自身免疫性疾病,其确切病因尚不清楚,不过越来越多的证据表明肠道微生物群在其发病机制中起作用。本研究旨在通过在使用DBA/1J和Aire/品系的胶原诱导性关节炎(CIA)小鼠模型中采用粪便微生物群移植(FMT),来研究肠道微生物群在RA发病和进展中的作用。小鼠接受来自健康供体、未接受过治疗的RA患者或处于复发期的接受过治疗的RA患者的FMT,随后通过16S rRNA测序、关节炎严重程度评分、组织学评估和全身炎症标志物来评估微生物群组成。研究结果揭示了FMT后各实验组不同的微生物群聚类模式,突出了菌株特异性定植效应。值得注意的是,在DBA/1J小鼠中,双歧杆菌属和副普雷沃菌属等菌属与关节炎严重程度呈正相关,而棒状杆菌属、肠道杆菌属和气味杆菌属呈负相关,表明它们可能具有保护作用。尽管存在这些微生物差异,但在FMT组之间观察到关节炎评分、爪部炎症或全身炎症的微小变化。这表明,虽然肠道微生物群的改变与RA发病机制有关,但采用更大的队列和全面的测序方法进行进一步研究对于阐明微生物群调节在自身免疫性疾病中的治疗潜力至关重要。

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