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Updated: Jul 4, 2025
A Proinflammatory, Degenerative Organ Culture Model to Simulate Early-Stage Intervertebral Disc Disease.
Published on: February 14, 2021
Causal associations between gut microbiota with intervertebral disk degeneration, low back pain, and sciatica: a
Miaojie Fang1,2,3,4,5, Wei Liu2, Zhan Wang1,3,4,5
1Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Shangcheng District, 310009, Hangzhou, People's Republic of China.
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.
Insights
This study reveals a causal link between specific gut microbes and their metabolic pathways with intervertebral disk degeneration (IVDD), low back pain (LBP), and sciatica, suggesting new therapeutic targets.
Area of Science:
- Microbiome research
- Genetics
- Epidemiology
Background:
- Gut microbiota alterations are suspected in intervertebral disk diseases.
- The causal link between gut microbiota and intervertebral disk degeneration (IVDD), low back pain (LBP), and sciatica remains unclear.
Purpose of the Study:
- To investigate the causal relationship between gut microbiota, its metabolic pathways, and the risk of IVDD, LBP, and sciatica.
- To identify potential microbial targets for intervention in intervertebral disk diseases.
Main Methods:
- Utilized Mendelian randomization (MR) analysis.
- Integrated genetic variation data for gut microbiota taxa and metabolic pathways from MiBioGen and Dutch Microbiome Project.
- Employed FinnGen consortium data for disease outcomes (IVDD, LBP, sciatica).
- Performed sensitivity analyses to ensure result robustness.
Main Results:
- Initial analysis identified 46 microbial taxa and 33 metabolic pathways causally associated with IVDD, LBP, and sciatica.
- After rigorous statistical correction (weighted median, MR-PRESSO, FDR), the genus *Eubacterium coprostanoligenes* group showed a stable causal effect on IVDD.
- Sensitivity analyses confirmed the absence of horizontal pleiotropy, heterogeneity, or reverse causation.
Conclusions:
- Specific gut microbial taxa and their metabolic pathways are causally implicated in the development of IVDD, LBP, and sciatica.
- These findings highlight the gut microbiota as a potential target for novel therapeutic strategies for intervertebral disk diseases.
- The study offers novel insights into the mechanistic role of the gut microbiome in the pathogenesis of spinal disorders.
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