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Updated: Jan 6, 2026
Microbiota Analysis Using Two-step PCR and Next-generation 16S rRNA Gene Sequencing
Published on: October 15, 2019
Associations between gut microbiota and multiple system atrophy: a Mendelian randomization study
Duo Wang1,2,3, Yuan-Yuan Zhao2, Yue Huang4,5
1Affiliated Hospital of Hebei University/School of Clinical Medicine of Hebei University, Baoding, China.
Background:
Multiple system atrophy (MSA) is a rare and progressive neurodegenerative disorder characterized by Parkinsonism, cerebellar dysfunction, and autonomic failure. Emerging evidence suggests that gut microbiota may contribute to neurodegeneration, but whether these associations are causal remains unclear.
Methods:
We conducted a two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary statistics of gut microbiota (n = 18,340) from the MiBioGen consortium and MSA (888 cases, 7,128 controls) from a recent European study. Single nucleotide polymorphisms associated with 196 bacterial taxa were selected as instrumental variables. The primary MR method was inverse-variance weighting, complemented by weighted median, MR-Egger, and MR-PRESSO. Sensitivity analyses assessed pleiotropy, heterogeneity, and robustness.
Results:
Six taxa showed nominal associations with MSA risk. Lentisphaeria (OR = 1.57, p = 0.035), Oscillospira (OR = 1.76, p = 0.034), Victivallales (OR = 1.57, p = 0.035), and Peptococcus (OR = 1.46, p = 0.025) were positively associated with increased risk, whereas Veillonella (OR = 0.40, p = 0.004) and Erysipelotrichaceae UCG-003 (OR = 0.60, p = 0.041) were associated with reduced risk. No evidence of pleiotropy or heterogeneity was found. None survived multiple-testing correction.
Conclusions:
This MR study provides hypothesis-generating evidence suggesting potential causal relationships between gut microbiota and MSA. These taxa nominate candidate microbial targets for future mechanistic and translational studies.
Insights
This study used Mendelian randomization to investigate the causal link between gut bacteria and Multiple System Atrophy (MSA). Certain gut bacteria were associated with increased or decreased MSA risk, suggesting potential therapeutic targets.
Area of Science:
- Neuroscience
- Microbiology
- Genetics
Background:
- Multiple System Atrophy (MSA) is a rare, progressive neurodegenerative disease impacting motor control and autonomic function.
- The gut microbiome's role in neurodegeneration is increasingly recognized, but causal links to MSA remain unproven.
Purpose of the Study:
- To investigate potential causal relationships between specific gut bacterial taxa and the risk of developing Multiple System Atrophy (MSA).
- To leverage Mendelian randomization (MR) to infer causality from observational data on gut microbiota and MSA.
Main Methods:
- A two-sample Mendelian randomization (MR) analysis was performed using genome-wide association study (GWAS) data for 196 gut microbial taxa and MSA.
- Inverse-variance weighting was the primary MR method, with complementary analyses including weighted median, MR-Egger, and MR-PRESSO.
- Sensitivity analyses were conducted to assess potential pleiotropy and heterogeneity, ensuring the robustness of the findings.
Main Results:
- Six bacterial taxa exhibited nominal associations with MSA risk.
- Lentisphaeria, Oscillospira, Victivallales, and Peptococcus were linked to an increased risk of MSA.
- Veillonella and Erysipelotrichaceae UCG-003 were associated with a reduced risk of MSA.
- No significant pleiotropy or heterogeneity was detected, though no associations survived multiple-testing correction.
Conclusions:
- This MR study provides preliminary evidence suggesting potential causal links between specific gut bacteria and MSA.
- The identified taxa represent potential microbial targets for future research into MSA mechanisms and treatments.
