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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