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Causal Relationships Between Gut Microbiota, Inflammatory Cells/Proteins, and Subarachnoid Hemorrhage: A Multi-omics Bidirectional Mendelian Randomization Study and Meta-analysis

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Abstract

Subarachnoid hemorrhage (SAH) is a neurological emergency that can lead to fatal outcomes. It occurs when bleeding happens in the subarachnoid space, a small gap between the arachnoid and pia mater. This condition results from the rupture of diseased or damaged blood vessels at the brain’s base or surface. This study combined various omics approaches with Mendelian randomization analysis, including MR-IVW, MR Egger, MR weight median, and MR weight mode, to generate preliminary results. It also employed reverse Mendelian randomization, treating SAH as the exposure. Finally, a meta-analysis was conducted to summarize these findings. The study found positive correlations between SAH and both GBPA-Pyridoxal 5 phosphate biosynthesis I (OR=1.48, 95% CI, 1.04–2.12) and GBPA-glucose biosynthesis I (OR=0.68, 95% CI, 0.52–0.90). Increased levels of urokinase-type plasma activator were also associated with SAH (OR=1.17, 95% CI, 1.04–1.32). Associations were observed with SAH for CD80 on CD62L+ plasmacytoid dendritic cells, CD80 on plasmacytoid dendritic cells, CD123 on CD62L+ plasmacytoid dendritic cells, and SSC-A on plasmacytoid dendritic cells. This study, through Mendelian randomization and meta-analysis, established links between SAH and four inflammatory cells, one inflammatory protein, and two gut microbiota-related pathways. These findings suggest potential treatment targets for SAH, highlighting the importance of modulating gut microbiota and utilizing anti-inflammatory drugs in its management.

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Data Availability

The datasets generated and/or analyzed during the current study are available in the in this website (https://pheweb.org/UKB-SAIGE/) and IEU OpenGWAS (https://gwas.mrcieu.ac.uk/), and Phenoscanner (http://www.phenoscanner.medschl.cam.ac.uk/).

Abbreviations

SAH:

Subarachnoid hemorrhage

MR:

Mendelian randomization

IVW:

Inverse variance weighted

SNPs:

Single nucleotide polymorphism

GBPA:

Gut bacterial pathway abundance

ICH:

Intracerebral Hemorrhage

TNF-α:

Tumor Necrosis Factor-alpha

IL-6:

Interleukin 6

IL-2:

Interleukin-2

NKs:

Natural killer cells

Tregs:

Tegulatory T cells

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Acknowledgements

We want to acknowledge the participants and investigators of the UK Biobank study.

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  1. Zhejiang Hospital, Zhejiang, China

    Congzhi Yan & Yun Li

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Yan, C., Li, Y. Causal Relationships Between Gut Microbiota, Inflammatory Cells/Proteins, and Subarachnoid Hemorrhage: A Multi-omics Bidirectional Mendelian Randomization Study and Meta-analysis. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04101-y

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