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Updated: Jul 4, 2025
Microbiota Analysis Using Two-step PCR and Next-generation 16S rRNA Gene Sequencing
Published on: October 15, 2019
Causal relationship between gut microflora and dementia: a Mendelian randomization study
Jinjie Fu1,2, Yuan Qin3,4, Lingyong Xiao3,4
1Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Background:
Numerous pertinent investigations have demonstrated a correlation between gut microflora (GM) and the occurrence of dementia. However, a causal connection between GM and dementia and its subtypes has not yet been clarified.
Objective:
To explore the causal association between GM and dementia, including its subtypes, a two-sample Mendelian randomization (TSMR) analysis was used.
Methods:
Our data comes from the Genome-Wide Association Study (GWAS). The principal approach employed for the Mendelian randomization study was the inverse-variance weighted method, supplemented by four methods: MR-Egger, weighted median, simple mode, and weighted mode. This was followed by Cochrane's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out as sensitivity analysis validation.
Results:
Twenty-one GMs associated with any dementia, Alzheimer's disease, vascular dementia, Lewy body dementia, Parkinson's disease, and dementia under other disease classifications were derived from the analysis, and 21 passed sensitivity tests.
Conclusion:
We confirmed the causal relationship between GM and dementia and its subtypes, derived specific flora associated with increased or decreased risk of dementia, and provided new ideas for preventive, diagnostic, and therapeutic interventions for dementia mediated by gut microbiota.
Insights
This study confirms a causal link between gut microflora (GM) and dementia. Specific gut bacteria influence dementia risk, offering new avenues for prevention and treatment.
Area of Science:
- Neuroscience
- Microbiology
- Genetics
Background:
- Emerging evidence suggests a link between gut microflora (GM) and dementia.
- A definitive causal relationship between GM and dementia subtypes remains unclear.
Purpose of the Study:
- To investigate the causal association between GM and dementia, including its subtypes.
- Utilize Mendelian randomization to explore gut microbiota's role in dementia etiology.
Main Methods:
- Employed a two-sample Mendelian randomization (TSMR) analysis using Genome-Wide Association Study (GWAS) data.
- Applied inverse-variance weighted (IVW) method, MR-Egger, weighted median, simple mode, and weighted mode.
- Conducted sensitivity analyses including Cochrane's Q test, MR-Egger intercept, MR-PRESSO, and leave-one-out.
Main Results:
- Identified 21 gut microflora (GM) significantly associated with dementia, Alzheimer's disease, vascular dementia, Lewy body dementia, and Parkinson's disease.
- All identified associations passed rigorous sensitivity tests, confirming robustness.
Conclusions:
- Established a causal relationship between specific gut microflora and dementia risk.
- Identified GM linked to increased or decreased dementia risk, informing novel interventions.
- Provided new insights for dementia prevention, diagnosis, and treatment strategies targeting the gut microbiota.
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