Table_2_Causal association of gut microbiota on spondyloarthritis and its subtypes: a Mendelian randomization analysis.xlsx

BackgroundDespite establishing an association between gut microbiota and spondyloarthritis (SpA) subtypes, the causal relationship between them remains unclear.
MethodsGut microbiota data were obtained from the MiBioGen collaboration, and SpA genome-wide association study (GWAS) summary data were obtained from the FinnGen collaboration. We conducted a two-sample Mendelian randomization (MR) analysis using the inverse-variance-weighted method supplemented with four additional MR methods (MR-Egger, weighted median, simple mode, and weighted mode). Pleiotropy and heterogeneity were also assessed. Reverse MR analysis was used to detect reverse causal relationships.
ResultsWe identified 23 causal links between specific gut microbiota taxa and SpA levels. Of these, 22 displayed nominal causal associations, and only one demonstrated a robust causal connection. Actinobacteria id.419 increased the risk of ankylosing spondylitis (AS) (odds ratio (OR) = 1.86 (95% confidence interval (CI): 1.29–2.69); p = 8.63E−04). The family Rikenellaceae id.967 was associated with a reduced risk of both AS (OR = 0.66 (95% CI: 0.47–0.93); p = 1.81E−02) and psoriatic arthritis (OR = 0.70 (95% CI: 0.50–0.97); p = 3.00E−02). Bacillales id.1674 increased the risk of AS (OR = 1.23 (95% CI: 1.00–1.51); p = 4.94E−02) and decreased the risk of enteropathic arthritis (OR = 0.56 (95% CI: 0.35–0.88); p = 1.14E−02). Directional pleiotropy, or heterogeneity, was not observed. No reverse causal associations were observed between the diseases and the gut microbiota.
ConclusionOur MR analysis suggested a genetic-level causal relationship between specific gut microbiota and SpA, providing insights into the underlying mechanisms behind SpA development mediated by gut microbiota.

研究背景 尽管已有研究证实肠道菌群与脊柱关节炎（spondyloarthritis, SpA）亚型之间存在关联，但二者之间的因果关系仍不明确。
研究方法 本研究的肠道菌群数据来源于MiBioGen协作组，脊柱关节炎全基因组关联研究（Genome-Wide Association Study, GWAS）汇总数据来源于FinnGen协作组。我们采用逆方差加权法，并辅以四种额外的孟德尔随机化（Mendelian randomization, MR）分析方法（MR-Egger法、加权中位数法、简单众数法与加权众数法）开展两样本孟德尔随机化分析。同时，我们还对多效性与异质性进行了评估，并通过反向孟德尔随机化分析检测是否存在反向因果关系。
研究结果 本研究共鉴定出23条特定肠道菌群分类群与脊柱关节炎水平之间的因果关联。其中22条仅显示名义上的因果关联，仅1条呈现出稳健的因果联系。放线菌门id.419会增加强直性脊柱炎（ankylosing spondylitis, AS）的发病风险（比值比（odds ratio, OR）=1.86，95%置信区间（confidence interval, CI）：1.29~2.69；p=8.63E−04）。里肯菌科id.967可降低强直性脊柱炎（OR=0.66，95%CI：0.47~0.93；p=1.81E−02）与银屑病关节炎（OR=0.70，95%CI：0.50~0.97；p=3.00E−02）的发病风险。芽孢杆菌目id.167会增加强直性脊柱炎的发病风险（OR=1.23，95%CI：1.00~1.51；p=4.94E−02），同时降低肠病性关节炎的发病风险（OR=0.56，95%CI：0.35~0.88；p=1.14E−02）。本研究未观察到定向多效性或异质性，也未发现疾病与肠道菌群之间存在反向因果关联。
研究结论 本项孟德尔随机化分析揭示了特定肠道菌群与脊柱关节炎之间存在遗传层面的因果关系，为阐明肠道菌群介导的脊柱关节炎发病潜在机制提供了新的见解。