A Mendelian randomization study to reveal gut-disc axis: causal associations between gut microbiota with intervertebral disc diseases.

Abstract

Emerging evidence suggests a link between gut microbiota and intervertebral disc diseases (IDDs); however, the causal relationships remain unclear. This study aimed to evaluate the causal effects of gut microbiota on the risk of cervical disc disorders (CDD), other intervertebral disc disorders (OIDD), pyogenic intervertebral disc infections, and discitis, shedding light on the potential "gut-disc axis". Genetic variation data for 202 gut microbiota taxa were obtained from the Dutch Microbiome Project, and disease outcome data were sourced from the FinnGen consortium. A Mendelian Randomization (MR) approach was employed to assess causal relationships, using genetic variants as instrumental variables. Sensitivity analyses, including tests for pleiotropy, heterogeneity, and reverse causation, ensured robust findings. The study identified 20 gut microbial taxa with significant associations to IDDs. Notably, taxa within the Erysipelotrichaceae family showed consistent protective effects against OIDD after Bonferroni correction (P < 0.05). Associations between several species and specific diseases, such as Alistipes senegalensis with CDD and Ruminococcus lactaris with discitis, were also observed. Sensitivity analyses confirmed no evidence of confounding or reverse causation. This study provides evidence of causal relationships between specific gut microbiota and IDDs, supporting the existence of a "gut-disc axis." The findings suggest that microbial dysbiosis may influence spinal health through systemic inflammation and immune regulation. These insights open new possibilities for microbiota-targeted interventions, such as probiotics or dietary modifications, to prevent or manage IDDs. However, further research is required to validate these therapeutic strategies.