Causal association of juvenile idiopathic arthritis or JIA-associated uveitis and gut microbiota: a bidirectional two-sample Mendelian randomisation study

Front Immunol. 2024 Jul 24:15:1356414. doi: 10.3389/fimmu.2024.1356414. eCollection 2024.

Abstract

Background: The gut microbiota significantly influences the onset and progression of juvenile idiopathic arthritis (JIA) and associated uveitis (JIAU); however, the causality remains unclear. This study aims to establish a causal link between gut microbiota and JIA or JIAU.

Methods: Using publicly available genome-wide association studies (GAWS) summary data, we conducted a two-sample Mendelian randomisation (MR) analysis employing various methods, namely inverse variance weighted (IVW), simple mode, weighted mode, weighted median and MR-Egger regression methods, to assess the causal association between JIA or JIAU and gut microbiota. Sensitivity analyses, including Cochrane's Q test, MR-Egger intercept test, leave-one-out analysis and MR-PRESSO, were performed to evaluate the robustness of the MR results. Subsequently, reverse MR analysis was conducted to determine causality between gene-predicted gut microbiota abundance and JIA or JIAU.

Results: The MR analysis revealed a causal association between gut microbiota abundance variations and JIA or JIAU risk. Specifically, the increased abundance of genus Ruminococcaceae UCG013 (OR: 0.055, 95%CI: 0.006-0.103, p = 0.026) and genus Ruminococcaceae UCG003 (β: 0.06, 95%CI: 0.003-0.117, p = 0.041) correlated with an increased risk of JIA, while genus Lachnospiraceae UCG001 (OR: 0.833, 95%CI: 0.699~0.993, p = 0.042) was associated with a reduced risk of JIA, among others. Sensitivity analysis confirmed MR analysis robustness.

Conclusions: This study provides substantial evidence supporting a causal association between genetically predicted gut microbiota and JIA or JIAU. It highlights the significant role of intestinal flora in JIA or JIAU development, suggesting their potential as novel biomarkers for diagnosis and prevention. These findings offer valuable insights to mitigate the impact of JIA or JIAU.

Keywords: Mendelian randomisation analysis; bidirectional; causality; gut microbiota; juvenile idiopathic arthritis; uveitis.

MeSH terms

  • Arthritis, Juvenile* / genetics
  • Arthritis, Juvenile* / microbiology
  • Gastrointestinal Microbiome* / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Mendelian Randomization Analysis*
  • Polymorphism, Single Nucleotide
  • Uveitis* / etiology
  • Uveitis* / genetics
  • Uveitis* / microbiology

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Department of Science and Technology of Guangdong Province, under the project ‘Efficacy and safety of the Jianer Jiedu Formula for the treatment of novel coronavirus infections in children-a real-world and randomised controlled study’ (No. 2023B1111020004); the State Administration of Traditional Chinese Medicine, under the project ‘a project for Chinese Medicine on Ying Lv’s Renowned Expert Inheritance Studio’ (No. E43729); Bureau of Science and Technology of Guangzhou Municipality, under the project ‘Mechanism Study on the Regulation of NLRP3-mediated Pyroptosis by Jianer Jiedu Formula for the Treatment of RSV Pneumonia in Children based on the Lingnan DampHeat Theory’ (No. 2024A03J0125); Guangdong Provincial Key Laboratory of Research on Emergency in TCM (No. 2023B1212060062); the Open Fund of Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine (No.KFKT02–006); and the 2024 Guangdong Renowned Traditional Chinese Medicine Practitioner Inheritance Studio Construction Project-Xu Youjia (No. 0102018005).