Table_12_Gut microbiota and common gastrointestinal diseases: a bidirectional two-sample Mendelian randomized study.XLSX

BackgroundSeveral recent studies have shown an association between gut microbiota and gastrointestinal diseases. However, the causal relationship between gut microbiota and gastrointestinal disorders is unclear.
MethodsWe assessed causal relationships between gut microbiota and eight common gastrointestinal diseases using Mendelian randomization (MR) analyses. IVW results were considered primary results. Cochrane’s Q and MR-Egger tests were used to test for heterogeneity and pleiotropy. Leave-one-out was used to test the stability of the MR results, and Bonferroni correction was used to test the strength of the causal relationship between exposure and outcome.
ResultsMR analyses of 196 gut microbiota and eight common gastrointestinal disease phenotypes showed 62 flora and common gastrointestinal diseases with potential causal relationships. Among these potential causal relationships, after the Bonferroni-corrected test, significant causal relationships remained between Genus Oxalobacter and CD (OR = 1.29, 95% CI: 1.13–1.48, p = 2.5 × 10–4, q = 4.20 × 10–4), and between Family Clostridiaceae1 and IBS (OR = 0.9967, 95% CI: 0.9944–0.9991, p = 1.3 × 10–3, q = 1.56 × 10–3). Cochrane’s Q-test showed no significant heterogeneity among the various single nucleotide polymorphisms (SNPs). In addition, no significant level of pleiotropy was found according to the MR-Egger.
ConclusionThis study provides new insights into the mechanisms of gut microbiota-mediated gastrointestinal disorders and some guidance for targeting specific gut microbiota for treating gastrointestinal disorders.

背景 近年多项研究已证实肠道菌群与胃肠道疾病存在关联，但二者间的因果关系仍未明确。
方法 本研究采用孟德尔随机化（Mendelian randomization, MR）分析方法，探究肠道菌群与8种常见胃肠道疾病之间的因果关系。以逆方差加权（Inverse Variance Weighted, IVW）结果作为主要分析结果；采用Cochrane Q检验与MR-Egger检验分别评估异质性与多效性；通过留一法（Leave-one-out）检验MR分析结果的稳定性，并利用邦费罗尼校正（Bonferroni correction）检验暴露因素与结局指标间因果关联的强度。
结果 本研究对196种肠道菌群与8种常见胃肠道疾病表型开展MR分析，共发现62种菌群与胃肠道疾病存在潜在因果关联。其中经邦费罗尼校正后，仍存在2项具有统计学意义的因果关联：草酸杆菌属（Genus Oxalobacter）与克罗恩病（Crohn's Disease, CD）（比值比（Odds Ratio, OR）=1.29，95%置信区间（Confidence Interval, CI）: 1.13–1.48，P=2.5×10⁻⁴，校正后q值=4.20×10⁻⁴）；梭菌科1（Family Clostridiaceae1）与肠易激综合征（Irritable Bowel Syndrome, IBS）（OR=0.9967，95%CI: 0.9944–0.9991，P=1.3×10⁻³，校正后q值=1.56×10⁻³）。Cochrane Q检验显示，各单核苷酸多态性（single nucleotide polymorphisms, SNPs）间未存在显著异质性；此外MR-Egger检验未检出显著多效性。
结论 本研究为阐明肠道菌群介导胃肠道疾病的发病机制提供了新视角，同时为针对特定肠道菌群的胃肠道疾病靶向治疗策略提供了参考依据。