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Causal associations between gut microbiota with intervertebral disk degeneration, low back pain, and sciatica: a Mendelian randomization study

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Abstract

Purpose

Although studies have suggested that gut microbiota may be associated with intervertebral disk disease, their causal relationship is unclear. This study aimed to investigate the causal relationship between the gut microbiota and its metabolic pathways with the risk of intervertebral disk degeneration (IVDD), low back pain (LBP), and sciatica.

Methods

Genetic variation data for 211 gut microbiota taxa at the phylum to genus level were obtained from the MiBioGen consortium. Genetic variation data for 105 taxa at the species level and 205 metabolic pathways were obtained from the Dutch Microbiome Project. Genetic variation data for disease outcomes were obtained from the FinnGen consortium. The causal relationships between the gut microbiota and its metabolic pathways and the risk of IVDD, LBP, and sciatica were evaluated via Mendelian randomization (MR). The robustness of the results was assessed through sensitivity analysis.

Results

Inverse variance weighting identified 46 taxa and 33 metabolic pathways that were causally related to IVDD, LBP, and sciatica. After correction by weighted median and MR-PRESSO, 15 taxa and nine pathways remained stable. After FDR correction, only the effect of the genus_Eubacterium coprostanoligenes group on IVDD remained stable. Sensitivity analyses showed no evidence of horizontal pleiotropy, heterogeneity, or reverse causation.

Conclusion

Some microbial taxa and their metabolic pathways are causally related to IVDD, LBP, and sciatica and may serve as potential intervention targets. This study provides new insights into the mechanisms of gut microbiota-mediated development of intervertebral disk disease.

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Acknowledgments

The authors express their gratitude to the participants and investigators of MiBioGen consortium, the Dutch Microbiome Project, and FinnGen consortium for sharing the GWAS summary data.

Funding

This study was supported by the National Natural Science Foundation of China (grant No. 81972514).

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Author notes

  1. Miaojie Fang and Wei Liu authors have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Shangcheng District, 310009, Hangzhou, People’s Republic of China

    Miaojie Fang, Zhan Wang, Jun Li, Shaojun Hu, Zilong Li, Weishan Chen & Ning Zhang

  2. Department of Orthopedics Surgery, International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, N1 Shangcheng Road, Yiwu, Zhejiang, People’s Republic of China

    Miaojie Fang & Wei Liu

  3. Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China

    Miaojie Fang, Zhan Wang, Jun Li, Shaojun Hu, Zilong Li, Weishan Chen & Ning Zhang

  4. Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China

    Miaojie Fang, Zhan Wang, Jun Li, Shaojun Hu, Zilong Li, Weishan Chen & Ning Zhang

  5. Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China

    Miaojie Fang, Zhan Wang, Jun Li, Shaojun Hu, Zilong Li, Weishan Chen & Ning Zhang

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  1. Miaojie Fang
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Fang, M., Liu, W., Wang, Z. et al. Causal associations between gut microbiota with intervertebral disk degeneration, low back pain, and sciatica: a Mendelian randomization study. Eur Spine J 33, 1424–1439 (2024). https://doi.org/10.1007/s00586-024-08131-x

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  • DOI: https://doi.org/10.1007/s00586-024-08131-x

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