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Investigating Alterations in Caecum Microbiota After Traumatic Brain Injury in Mice
Published on: September 19, 2019
Causal relationship between gut microbiota and intracranial hemorrhage: A two-sample Mendelian randomization study
Jiameng Jia1, Lin Zhou2, Nan Wang2
1Rehabilitation Medicine Department, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Abstract:
Patients with intracranial hemorrhage (ICH) usually have an imbalance in the gut microbiota (GM); however, whether this is a causal correlation remains unclear. This study used summary data from an open genome-wide association study to conduct double-sample Mendelian randomization (MR) to test the causal correlation between GM and ICH. First, we used a cutoff value of P < 10E-5 to select single nucleotide polymorphisms critical for each GM. Inverse variance weighted, weighted median, and MR-PRESSO methods were used to evaluate the strength of this causal association. Finally, functional maps and annotations from genome-wide association studies were used to determine the biological functions of the genes. MR analysis revealed that Rikenellaceae RC9 gut group was significantly positively correlated with ICH risk. For every unit increase in Rikenellaceae RC9 gut group, the relative risk of ICH increased by 34.4%(P = 4.62E-04). Rhodospirillales, Terrisporobacter, Veillonellaceae, Coprococcus 3, unknown genus, Alphaproteobacteria, and Allisonella groups were negatively correlated with the risk of ICH, while Anaerofilum, Eubacteriumbrachy group, Clostridia, Howardella, and Romboutsia were negatively correlated with the risk of ICH. Nonetheless, the specific role of single nucleotide polymorphisms gene enrichment requires further investigation. This study suggests the causal effect on ICH. The discovery of >10 GMs associated with ICH could be used to prevent and treat ICH.
Insights
Gut microbiota imbalances may causally influence intracranial hemorrhage (ICH) risk. Certain gut bacteria, like Rikenellaceae RC9, increase ICH risk, while others may offer protection, suggesting novel therapeutic targets.
Area of Science:
- Microbiome research
- Genetics
- Neurology
Background:
- Intracranial hemorrhage (ICH) is often associated with gut microbiota (GM) dysbiosis.
- The causal relationship between GM and ICH remains largely undetermined.
Purpose of the Study:
- To investigate the potential causal link between gut microbiota composition and the risk of intracranial hemorrhage (ICH).
- To identify specific gut microbial taxa associated with ICH risk using a robust genetic approach.
Main Methods:
- Utilized a two-sample Mendelian randomization (MR) design leveraging summary statistics from genome-wide association studies.
- Selected single nucleotide polymorphisms (SNPs) associated with gut microbial traits (P < 10E-5).
- Employed inverse variance weighted, weighted median, and MR-PRESSO methods for causal inference analysis.
Main Results:
- Mendelian randomization analysis indicated a significant positive causal association between the Rikenellaceae RC9 gut group and ICH risk (RR=1.344, P=4.62E-04).
- Several other gut microbial taxa, including Rhodospirillales, Terrisporobacter, Veillonellaceae, Coprococcus 3, unknown genus, Alphaproteobacteria, Allisonella, Anaerofilum, Eubacterium brachy group, Clostridia, Howardella, and Romboutsia, showed negative correlations with ICH risk.
- Functional enrichment analysis of associated genes requires further investigation.
Conclusions:
- This study provides evidence for a causal effect of gut microbiota on intracranial hemorrhage risk.
- The identification of over ten gut microbial taxa associated with ICH offers potential targets for preventative and therapeutic strategies.
