This study investigates the causal relationships between gut microbiota, cytokines, and five types of dementia (Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, vascular dementia, and Parkinson's disease dementia) using Mendelian randomization (MR). The research analyzed genome-wide association study (GWAS) summary data to identify genetic variants associated with gut microbiota and cytokines, and then used MR to assess their causal effects on dementia. The study also explored whether cytokines act as mediators in the pathway from gut microbiota to dementia. The results showed 20 positive and 16 negative causal effects between gut microbiota and dementia, and five positive and four negative causal effects between cytokines and dementia. Cytokines were not found to be mediating factors in the pathway from gut microbiota to dementia. The study found that specific gut microbiota taxa were associated with increased or decreased risks of each dementia type, while certain cytokines were linked to increased risks of dementia. However, no causal effect was found between gut microbiota and cytokines, suggesting that cytokines do not mediate the relationship between gut microbiota and dementia. The study also examined bidirectional causal effects between dementia and gut microbiota/cytokines, finding some associations, but no significant reverse effects. The findings suggest that gut microbiota and cytokines are causally linked to dementia, but cytokines do not play a mediating role in the pathway from gut microbiota to dementia. The study highlights the potential role of gut microbiota in dementia development and the need for further research to understand the mechanisms by which gut microbiota influence dementia. The study is limited by the small sample sizes for some dementia subtypes and the use of blood-derived cytokine data rather than cerebrospinal fluid. Overall, the study provides important insights into the causal relationships between gut microbiota, cytokines, and dementia.This study investigates the causal relationships between gut microbiota, cytokines, and five types of dementia (Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, vascular dementia, and Parkinson's disease dementia) using Mendelian randomization (MR). The research analyzed genome-wide association study (GWAS) summary data to identify genetic variants associated with gut microbiota and cytokines, and then used MR to assess their causal effects on dementia. The study also explored whether cytokines act as mediators in the pathway from gut microbiota to dementia. The results showed 20 positive and 16 negative causal effects between gut microbiota and dementia, and five positive and four negative causal effects between cytokines and dementia. Cytokines were not found to be mediating factors in the pathway from gut microbiota to dementia. The study found that specific gut microbiota taxa were associated with increased or decreased risks of each dementia type, while certain cytokines were linked to increased risks of dementia. However, no causal effect was found between gut microbiota and cytokines, suggesting that cytokines do not mediate the relationship between gut microbiota and dementia. The study also examined bidirectional causal effects between dementia and gut microbiota/cytokines, finding some associations, but no significant reverse effects. The findings suggest that gut microbiota and cytokines are causally linked to dementia, but cytokines do not play a mediating role in the pathway from gut microbiota to dementia. The study highlights the potential role of gut microbiota in dementia development and the need for further research to understand the mechanisms by which gut microbiota influence dementia. The study is limited by the small sample sizes for some dementia subtypes and the use of blood-derived cytokine data rather than cerebrospinal fluid. Overall, the study provides important insights into the causal relationships between gut microbiota, cytokines, and dementia.