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Review
. 2025 Mar 6:15:1433131.
doi: 10.3389/fcimb.2025.1433131. eCollection 2025.

Deconstruct the link between gut microbiota and neurological diseases: application of Mendelian randomization analysis

Jingqiu Li #  1 , Xinyang Hu #  2 , Xinyu Tao #  2 , Yuming Li #  2 , Wan Jiang  3 , Mingtao Zhao  1 , Zhehui Ma  1 , Bangjie Chen  2 , Shuyan Sheng  2 , Jiaye Tong  2 , Haibo Zhang  2 , Bing Shen  4 , Xiaomei Gao  2
Affiliations
Review

Deconstruct the link between gut microbiota and neurological diseases: application of Mendelian randomization analysis

Jingqiu Li et al. Front Cell Infect Microbiol. .

Abstract

Background: Recent research on the gut-brain axis has deepened our understanding of the correlation between gut bacteria and the neurological system. The inflammatory response triggered by gut microbiota may be associated with neurodegenerative diseases. Additionally, the impact of gut microbiota on emotional state, known as the "Gut-mood" relationship, could play a role in depression and anxiety disorders.

Results: This review summarizes recent data on the role of gut-brain axis in the pathophysiology of neuropsychiatric and neurological disorders including epilepsy, schizophrenia, Alzheimer's disease, brain cancer, Parkinson's disease, bipolar disorder and stroke. Also, we conducted a Mendelian randomization study on seven neurological disorders (Epilepsy, schizophrenia, Alzheimer's disease, brain cancer, Parkinson's disease, bipolar disorder and stroke). MR-Egger and MR-PRESSO tests confirmed the robustness of analysis against horizontal pleiotropy.

Conclusions: By comparing the protective and risk factors for neurological disorders found in our research and other researches, we can furtherly determine valuable indicators for disease evolution tracking and potential treatment targets. Future research should explore extensive microbiome genome-wide association study datasets using metagenomics sequencing techniques to deepen our understanding of connections and causality between neurological disorders.

Keywords: Mendelian randomization; genetics; gut flora; inflammation; neurological disorders; single nucleotide polymorphisms.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Summary of the main assumptions and methods used in MR analysis.
Figure 2
Figure 2
Causal analysis of GM on Epilepsy. (A) All results of MR analysis and sensitivity analysis between GM and Epilepsy; (B) MR results of GM taxa with a causal relationship to Epilepsy.
Figure 3
Figure 3
Causal analysis of GM on Schizophrenia. (A) All results of MR analysis and sensitivity analysis between GM and Schizophrenia; (B) MR results of GM taxa with a causal relationship to Schizophrenia.
Figure 4
Figure 4
Causal analysis of GM on Alzheimer’s disease. (A) All results of MR analysis and sensitivity analysis between GM and Alzheimer’s disease; (B) MR results of GM taxa with a causal relationship to Alzheimer’s disease.
Figure 5
Figure 5
Causal analysis of GM on Brain cancer. (A) All results of MR analysis and sensitivity analysis between GM and Brain cancer; (B) MR results of GM taxa with a causal relationship to Brain cancer.
Figure 6
Figure 6
Causal analysis of GM on Parkinson’s disease. (A) All results of MR analysis and sensitivity analysis between GM and Parkinson’s disease; (B) MR results of GM taxa with a causal relationship to Parkinson’s disease.
Figure 7
Figure 7
Causal analysis of GM on Bipolar disorder. (A) All results of MR analysis and sensitivity analysis between GM and Bipolar disorder; (B) MR results of GM taxa with a causal relationship to Bipolar disorder.
Figure 8
Figure 8
Causal analysis of GM on Stroke. (A) All results of MR analysis and sensitivity analysis between GM and Stroke; (B) MR results of GM taxa with a causal relationship to Stroke.
Figure 9
Figure 9
Causal relationship between gut microbiota and neurological diseases and possible links between gut microbiota.
See this image and copyright information in PMC

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