Gut microbiota, circulating cytokines and dementia: a Mendelian randomization study

Abstract

Background: Some studies have shown that gut microbiota may be associated with dementia. However, the causal effects between gut microbiota and different types of dementia and whether cytokines act as a mediator remain unclear.

Methods: Gut microbiota, cytokines, and five dementia types, including Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy body (DLB), vascular dementia (VD), and Parkinson's disease dementia (PDD) were identified from large-scale genome-wide association studies (GWAS) summary data. We used Mendelian randomization (MR) to investigate the causal relationships between gut microbiota, cytokines, and five types of dementia. Inverse variance weighting (IVW) was used as the main statistical method. In addition, we explored whether cytokines act as a mediating factor in the pathway from gut microbiota to dementia.

Results: There were 20 positive and 16 negative causal effects between genetic liability in the gut microbiota and dementia. Also, there were five positive and four negative causal effects between cytokines and dementias. Cytokines did not act as mediating factors.

Conclusions: Gut microbiota and cytokines were causally associated with five types of dementia, and cytokines seemed not to be the mediating factors in the pathway from gut microbiota to dementia.

Keywords: Cytokines; Dementia; Gut microbiota; Mendelian randomization.

Fig. 1

Study overview. Step 1A represents the causal effects of gut microbiota on dementia. Step 1B represents the bi‑directional causal effects between gut microbiota and dementia. Step 2A represents the causal effects of cytokines on dementia. Step 2B represents the bi‑directional causal effects between cytokines and dementia. Step 3 represents the mediating analysis of cytokines in the pathway from the gut microbiota to dementia: path c was the total effect of gut microbiota on dementia; path b was the causal effect of cytokines on dementia; path a was the causal effect of gut microbiota on cytokines

Fig. 2

Mendelian randomization results of causal effects between gut microbiotas and five subtypes of dementia

Fig. 3

Mendelian randomization results of causal effects between cytokines and five subtypes of dementia