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. 2024 Mar 25:15:1357303.
doi: 10.3389/fmicb.2024.1357303. eCollection 2024.

Genetically predicted causal effects of gut microbiota on spinal pain: a two-sample Mendelian randomization analysis

Shuangwei Hong #  1   2 , Longhao Chen #  1   2 , Xingchen Zhou #  1   2 , Yuanshen Huang #  1   2 , Yu Tian  1   2 , Huijie Hu  1   2 , Bei Yu  1   2 , Hongjiao Wu  3 , Chao Yang  1 , Zhizhen Lv  1   2   4 , Lijiang Lv  1   2   4
Affiliations

Genetically predicted causal effects of gut microbiota on spinal pain: a two-sample Mendelian randomization analysis

Shuangwei Hong et al. Front Microbiol. .

Abstract

Background: Observational studies have hinted at a correlation between the gut microbiota and spinal pain (SP). However, the impact of the gut microbiota on SP remains inconclusive.

Methods: In this study, we employed a two-sample Mendelian randomization (MR) analysis to explore the causal relationship between the gut microbiota and SP, encompassing neck pain (NP), thoracic spine pain (TSP), low back pain (LBP), and back pain (BP). The compiled gut microbiota data originated from a genome-wide association study (GWAS) conducted by the MiBioGen consortium (n = 18,340). Summary data for NP were sourced from the UK Biobank, TSP from the FinnGen Biobank, and LBP from both the UK Biobank and FinnGen Biobank. Summary data for BP were obtained from the UK Biobank. The primary analytical approach for assessing causal relationships was the Inverse Variance Weighted (IVW) method, supplemented by various sensitivity analyses to ensure result robustness.

Results: The IVW analysis unveiled 37 bacterial genera with a potential causal relationship to SP. After Benjamini-Hochberg corrected test, four bacterial genera emerged with a strong causal relationship to SP. Specifically, Oxalobacter (OR: 1.143, 95% CI 1.061-1.232, P = 0.0004) and Tyzzerella 3 (OR: 1.145, 95% CI 1.059-1.238, P = 0.0007) were identified as risk factors for LBP, while Ruminococcaceae UCG011 (OR: 0.859, 95% CI 0.791-0.932, P = 0.0003) was marked as a protective factor for LBP, and Olsenella (OR: 0.893, 95% CI 0.839-0.951, P = 0.0004) was recognized as a protective factor for low back pain or/and sciatica. No significant heterogeneity or horizontal pleiotropy was observed through alternative testing methods.

Conclusion: This study establishes a causal relationship between the gut microbiota and SP, shedding light on the "gut-spine" axis. These findings offer novel perspectives for understanding the etiology of SP and provide a theoretical foundation for potential interventions targeting the gut microbiota to prevent and treat SP.

Keywords: Mendelian randomization; back pain; causality; gut microbiota; low back pain; neck pain; spinal pain; thoracic spine pain.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Three assumptions and flowchart for Mendelian randomization study.
FIGURE 2
FIGURE 2
Forest plot of causality between gut microbiota and risk of neck pain.
FIGURE 3
FIGURE 3
Forest plot of causality between gut microbiota and risk of thoracic spine pain.
FIGURE 4
FIGURE 4
Forest plot of causality between gut microbiota and risk of low back pain with/without lower limb pain.
FIGURE 5
FIGURE 5
Forest plot of causality between gut microbiota and risk of back pain.
See this image and copyright information in PMC

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