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Gut Microbiota and White Matter Integrity: A Two-Sample Mendelian Randomization Analysis
Lan Zhang1,2,3, Xiao-Wei Pang1,2,3, Lu-Yang Zhang1,2,3
1Department of Neurology, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic infectious Diseases, Huazhong University of Science and Technology, Wuhan 430030, China.
Abstract:
The causal relationship between gut microbiota (GM) and white matter injury and communication remains unclear. We aimed to scrutinize the plausible causal impact of GM on white matter hyperintensities (WMHs), white matter microstructure, white matter connectivity, and multiple neurological diseases via Mendelian randomization study. We identified four WMH-related bacterial taxa, including class Melainabacteria, order Gastranaerophilales, family Alcaligenaceae, and genus Ruminiclostridium 6 In addition, three bacterial taxa were discovered that have consistent effect on multiple aspects of white matter microstructure. Furthermore, we found 12 strong associations between genetic liability in GM and white matter connectivity. Among these bacterial taxa, the family Clostridiaceae 1 demonstrated a protective effect against ischemic stroke (IS). The genus Barnesiella showed protective effect on IS and small vessel stroke while posed a risk effect on neuromyelitis optica spectrum disorder (NMOSD), as well as on aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD). The order Desulfovibrionales and family Desulfovibrionaceae showed protective effect against cardioembolic stroke, and the genus Ruminococcus gnavus group showed a protective effect on amyotrophic lateral sclerosis. In terms of the mapped genes of statistically significant bacterial taxa, genes such as CPNE1, PIGU, MED22, SURF6, DOCK10, and COPS3 exhibited a significant causal correlation with the corresponding white matter connectivity. This study demonstrated a genetically predicted causal relationship between GM and WMH, white matter microstructure, white matter connectivity, and multiple neurological diseases, based on GWAS data from mixed-sex cohorts without sex-stratified summary statistics. These findings highlight the potential role of GM in influencing brain structural integrity.
Insights
This study reveals a genetically predicted causal link between gut microbiota and white matter integrity. Specific gut bacteria influence white matter hyperintensities, microstructure, connectivity, and neurological diseases.
Area of Science:
- Neuroscience
- Microbiology
- Genetics
Background:
- The gut microbiota's role in brain health, particularly white matter integrity and neurological diseases, is not fully understood.
- Existing research suggests potential links, but causal relationships require robust investigation.
Purpose of the Study:
- To investigate the causal impact of gut microbiota on white matter hyperintensities, microstructure, connectivity, and neurological diseases using Mendelian randomization.
- To identify specific bacterial taxa and genetic factors associated with white matter changes and neurological conditions.
Main Methods:
- Utilized Mendelian randomization study design.
- Analyzed genome-wide association study (GWAS) data for gut microbiota and neurological traits.
- Identified statistically significant associations between genetic liability of gut microbiota and white matter characteristics.
Main Results:
- Identified specific bacterial taxa associated with white matter hyperintensities (e.g., Melainabacteria, Ruminiclostridium 6).
- Found bacterial taxa influencing white matter microstructure and connectivity.
- Established associations between gut microbiota and neurological diseases like ischemic stroke, neuromyelitis optica spectrum disorder, and amyotrophic lateral sclerosis.
- Highlighted specific genes (e.g., CPNE1, PIGU) causally correlated with white matter connectivity.
Conclusions:
- Demonstrated a genetically predicted causal relationship between gut microbiota and white matter integrity.
- Highlighted the potential of gut microbiota as a modifiable factor influencing brain structural integrity and neurological disease risk.
- Findings underscore the gut-brain axis's importance in neurological health.
