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The role of HLA-DR on plasmacytoid dendritic cells in mediating the effects of Butyrivibrio gut microbiota on Parkinson’s disease

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Abstract

Background

Parkinson’s disease (PD) is viewed as a progressively deteriorating neurodegenerative disorder, the exact etiology of which remains not fully deciphered to this date. The gut microbiota could play a crucial role in PD development by modulating the human immune system.

Objective

This study aims to explore the relationship between gut microbiota and PD, focusing on how immune characteristics may both directly and indirectly influence their interaction.

Methods

Utilizing cumulative data from genome-wide association studies (GWAS), our research conducted a two-sample Mendelian randomization (MR) analysis to clarify the association between the gut microbiome and PD. Additionally, by employing a two-step MR approach, we assessed the impact of gut microbiota on PD development via immune characteristics and quantified HLA-DR mediation effect on plasmacytoid dendritic cells (pDCs).

Results

We discovered significant associations between PD and microbiota, comprising one class, one order, two families, and two genera. Furthermore, we explored the extent to which HLA-DR on pDCs mediates the effect of Butyrivibrio gut microbiota on PD.

Conclusion

Our study emphasizes the complex interactions between the gut microbiota, immune characteristics, and PD. The relationships and intermediary roles identified in our research provide important insights for develo** potential therapies that target the gut microbiome to alleviate symptoms in PD patients.

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Data availability

The comprehensive dataset utilized in this research can be accessed publicly through https://gwas.mrcieu.ac.uk/. Study data are accessible upon request from the corresponding author.

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Acknowledgements

The authors express their gratitude to all participants and researchers involved in the GWAS study, the IEU OpenGWAS project, the NHGRI-EBI Catalog of Human Genome-Wide Association Studies, and other GWAS datasets for their contributions and data sharing.

Funding

This research was supported by the Autonomous Region Key Research and Development Project (Grant No. 2023B03003), the Tian-Shan Talent Program (Grant No. 2022TSYCLJ0066), the National Natural Science Foundation of China (Grant No. 82371258), and the Central Guiding Local Science and Technology Development Special Fund Project (Grant No. ZYYD2022C17).

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Authors and Affiliations

  1. Key Laboratory of the Second Affiliated Hospital of **njiang Medical University, Urumqi, **njiang, China

    Zihao Wang, Huan **a, Tingting Feng, Adilai Aibibuli & Mingyang Zhang

  2. Department of Neurology, Second Affiliated Hospital of **njiang Medical University, Urumqi, **njiang, China

    **nling Yang

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  1. Zihao Wang
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Contributions

Zihao Wang: research design and manuscript drafting. Huan **a and Tingting Feng: data analysis. Adilai Aibibuli: manuscript editing and language polishing.**nling Yang and Mingyang Zhang: research design and peer review. All authors have reviewed and approved the final version of the manuscript.

Corresponding author

Correspondence to **nling Yang.

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The utilized data were sourced from accessible online public databases, and the submission has already received approval from the hospital’s ethics committee report in accordance, rendering further ethical approval unnecessary.

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This study did not involve any human experiments. All analyses were based on publicly available whole-genome association study data.

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Wang, Z., **a, H., Feng, T. et al. The role of HLA-DR on plasmacytoid dendritic cells in mediating the effects of Butyrivibrio gut microbiota on Parkinson’s disease. Neurol Sci (2024). https://doi.org/10.1007/s10072-024-07467-y

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