Shenzhen Children's Hospital, Shenzhen, China.
Department of Internal Medicine V Hematology Oncology Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.
J Cell Mol Med. 2024 Oct;28(20):e70183. doi: 10.1111/jcmm.70183.
There is increasing evidence of a significant association between the gut microbiome and juvenile idiopathic arthritis (JIA). However, whether this association is causal remains to be determined. This study was a two-sample Mendelian randomization (MR) study using publicly available genome-wide association study (GWAS) summary data to investigate the causal relationship between the gut microbiome and JIA. We used summary data on gut flora and JIA obtained from genome-wide association studies (GWAS) from MiBioGen and NHGRI-EBI, using inverse variance weighting as the main method to analyse causality in the TSMR causality analysis. To check the stability of the TSMR results, we performed several sensitivity analyses and assessed the presence of reverse causality through a reverse TSMR analysis. We calculated the degree of sample overlap where applicable. The current TSMR analyses identified four bacterial taxa associated with JIA. Specifically, two bacteria, Catenibacterium (p = 2 × 10-2) and Holdemania (p = 4 × 10-2), were negatively associated with the risk of developing JIA, suggesting a protective effect, while Olsenella (p = 1 × 10-2) and Rikenellaceae (RC9gutgroup) (p = 1 × 10-2) were positively associated with the risk of JIA, suggesting that these two bacteria may be risk factors for JIA. However, the results for Catenibacterium and Holdemania should be interpreted with caution due to instability observed in 'leave-one-out' sensitivity analyses. Reverse TSMR analyses found no evidence of reverse causality between JIA and gut flora. Our confirmation of a causal relationship between gut flora and JIA provides an innovative perspective for the study of JIA: targeting and modulating dysregulation of specific bacterial taxa to prevent and treat JIA.
越来越多的证据表明肠道微生物群与青少年特发性关节炎（JIA）之间存在显著关联。然而，这种关联是否具有因果关系仍有待确定。本研究是一项两样本孟德尔随机化（MR）研究，使用公开的全基因组关联研究（GWAS）汇总数据来研究肠道微生物群与 JIA 之间的因果关系。我们使用了 MiBioGen 和 NHGRI-EBI 的全基因组关联研究（GWAS）中获得的肠道菌群和 JIA 的汇总数据，使用逆方差加权作为主要方法，通过 TSMR 因果分析来分析因果关系。为了检查 TSMR 结果的稳定性，我们进行了几次敏感性分析，并通过反向 TSMR 分析评估了反向因果关系的存在。在适用的情况下，我们计算了样本重叠的程度。目前的 TSMR 分析确定了与 JIA 相关的四种细菌分类群。具体而言，两种细菌，Catenibacterium（p=2×10-2）和Holdemania（p=4×10-2）与 JIA 发病风险呈负相关，表明具有保护作用，而 Olsenella（p=1×10-2）和 Rikenellaceae（RC9gutgroup）（p=1×10-2）与 JIA 发病风险呈正相关，表明这两种细菌可能是 JIA 的风险因素。然而，由于在“留一法”敏感性分析中观察到的不稳定性，应该谨慎解释 Catenibacterium 和 Holdemania 的结果。反向 TSMR 分析未发现 JIA 和肠道菌群之间存在反向因果关系的证据。我们确认了肠道菌群与 JIA 之间的因果关系，为 JIA 的研究提供了一个创新的视角：靶向和调节特定细菌分类群的失调，以预防和治疗 JIA。
