Mendelian randomization analysis reveals causal relationships between gut microbiome and optic neuritis
Mendelian randomization analysis reveals causal relationships between gut microbiome and optic neuritis
复制标题
孟德尔随机分析揭示肠道微生物组与视神经炎之间的因果关系
DOI：
10.1007/s00439-022-02514-0
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发表时间：
2022-12-28
期刊：
影响因子：
5.3
通讯作者：
You, Zhipeng
中科院分区：
文献类型：
--
作者：
Liu, Kangcheng;Wu, Pengfei;You, Zhipeng
背景目前尚不清楚肠道微生物群（GM）是否通过“肠-脑“轴和“肠-视网膜“轴影响视神经炎（ON）的风险。为了检验GM和ON之间的因果关系，我们进行了孟德尔随机化（MR）研究。方法对24个群体的18,340个样本进行了196个转基因分类群的全基因组关联研究（GWAS）。ON结局选自FinnGen GWAS（951例ON病例和307，092例对照）。此外，基于英国生物样本库（UKB）的GWAS（105例ON病例和456，243例对照）用于进一步探索。进行逆方差加权（IVW）估计其对ON风险的影响，并在敏感性分析中评估MR假设。结果在196个GM分类群中，IVW结果证实消化球菌科（P = 2.17 × 10（-3））、Hungatella属（P = 4.57 × 10（-3））和直肠真杆菌属（P = 0.02）与基于Finngen GWAS的ON风险相关。根据UKB的数据，霍氏真杆菌属（Eubacterium_hallii_group）（P = 1.50 × 10（-3））和瘤胃球菌属（Ruminococcaceae_UCG_002）（P = 0.02）与ON的风险相关。异源性（P > 0.05）和多效性（P > 0.05）分析证实了MR结果的稳健性。结论GM可能通过“肠-脑“轴和“肠-视网膜“轴影响ON的发病风险。但GM与ON关系的相关机制尚需进一步研究证实。
Background It is unclear whether gut microbiota (GM) affects the risk of optic neuritis (ON) through the "gut-brain " axis and the "gut-retina " axis. To examine the causal relationship between GM and ON, we conducted Mendelian randomization (MR) study. Methods Up to 18,340 samples of 24 population-based cohorts were included in genome-wide association study (GWAS) of 196 GM taxa. ON outcomes were selected from the FinnGen GWAS (951 ON cases and 307,092 controls). In addition, the GWAS based on UK Biobank (UKB) (105 ON cases and 456,243 controls) was used for further exploration. Inverse variance weighted (IVW) was carried out to estimate their effects on ON risk and the MR assumptions were evaluated in sensitivity analyses. Results Among the 196 GM taxa, the IVW results confirmed that Family -Peptococcaceae (P = 2.17 x 10(-3)), Genus- Hungatella (P = 4.57 x 10(-3)) and genus-Eubacterium_rectale_group (P = 0.02) were correlated with the risk of ON based on Finngen GWAS. Based on data from UKB, Genus- Eubacterium_hallii_group (P = 1.50 x 10(-3)) and Genus- Ruminococcaceae_UCG_002 (P = 0.02) were correlated with the risk of ON. At the phylum, class and order levels, no GM taxa were causally related to ON (P > 0.05). Heterogeneity (P > 0.05) and pleiotropy (P > 0.05) analysis confirmed the robustness of the MR results. Conclusion Our MR findings support the causal effect of specific GM taxa on ON. GM may affect the risk of ON through the "gut-brain " axis and the "gut-retina " axis. However, further research is needed to confirm the relevant mechanism of the relationship between GM and ON.