目的：探讨肠道菌群与额颞叶痴呆之间的潜在因果关系。方法：利用 MiBioGen、IEU OpenGWAS
project网站分别获取肠道菌群与额颞叶痴呆全基因组关联研究（GWAS）数据，选取与肠道菌群及额颞叶痴
呆相关的遗传变异作为工具变量，分别采用MR分析的常用方法包括逆方差加权法（inverse variance weight
ed，IVW）、加权中位数法（weighted median，WME）、MR-Egger法、简单模式法（simple mode，SM）和加权模
式法（weighted mode，WM）进行孟德尔随机化分析，最终通过逆方差加权法P值确定肠道菌群与额颞叶痴
呆因果关系。同时采用Q检验检验异质性，pleiotropy函数检验多效性，mrpresso检测水平基因多效性，Stei
ger检验方向性。结果：筛选出与额颞叶痴呆相关的遗传变异作为工具变量，瘤胃球菌与额颞叶痴呆之间存
在因果关联（OR=0.134，95%CI 0.028～0.637，P＜0.05），直肠中梭菌属的Family_XIII_UCG_001与额颞叶痴
呆之间存在因果关联（OR=10.672，95%CI 2.001～56.921，P＜0.05），瘤胃球菌、直肠中梭菌属的 Fami
ly_XIII_UCG_001 与额颞叶痴呆的因果关联不存在异质性（P＞0.05）；瘤胃球菌、直肠中梭菌属的 Fami
ly_XIII_UCG_001与额颞叶痴呆的不存在水平多效性的影响（P＞0.05）；mrpresso检测水平基因多效性（P＞
0. 05）；steiger检验瘤胃球菌、直肠中梭菌属的Family_XIII_UCG_001与额颞叶痴呆方向性（P＜0. 05）。结
论：瘤胃球菌与额颞叶痴呆存在负向因果关系、直肠中梭菌属的Family_XIII_UCG_001与额颞叶痴呆存在
正向因果关系。
To explore the potential causal relationship between gut microbiota and fronto-temporal
dementia (FTD). Methods: Genome-wide association study (GWAS) data for gut microbiota and FTD were
obtained from the MiBioGen and IEU OpenGWAS project websites, respectively. Genetic variants associated
with both gut microbiota and FTD were selected as instrumental variables. Commonly used methods in
Mendelian randomization (MR) analysis, including the inverse variance weighted (IVW) method, weighted
median (WME) method, MR-Egger method, simple mode (SM) method, and weighted mode (WM) method,
were employed for the MR analysis. The causal relationship between gut microbiota and FTD was ultimately
determined based on the P-value derived from the IVW method. Heterogeneity was assessed using the Q test,
pleiotropy was evaluated using the pleiotropy function, horizontal pleiotropy was detected using MR-PRESSO,
and directionality was tested using the Steiger test. Results: Genetic variants associated with FTD were
screened and used as instrumental variables. A causal association was identified between Ruminococcus and
FTD (OR=0.134, 95% CI: 0.028～0.637, P<0.05), as well as between Family_XIII_UCG_001 (a member of the
Clostridium genus in the rectum) and FTD (OR=10.672, 95% CI: 2.001～56.921, P<0.05). No heterogeneity was
observed in the causal associations of Ruminococcus and Family_XIII_UCG_001 with FTD (P>0.05).
Additionally, no horizontal pleiotropic effects were detected for these associations (P>0.05). MR-PRESSO
analysis confirmed the absence of horizontal pleiotropy (P>0.05), and the Steiger test validated the directionality
of the causal relationships between Ruminococcus, Family_XIII_UCG_001, and FTD (P<0.05). Conclusion: A
negative causal relationship exists between Ruminococcus and FTD, while a positive causal relationship exists
between Family_XIII_UCG_001 (of the Clostridium genus in the rectum) and FTD.
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