Exploring the role of gut microbiota in intervertebral disc degeneration: insights from bidirectional Mendelian randomization analysis

Abstract

Objective: Although previous studies have indicated a potential association between the gut microbiota and intervertebral disc degeneration (IVDD), the precise nature of this relationship remains unclear. The objective of this study is to further explore the potential causal relationship between gut microbiota and IVDD using a bidirectional Mendelian randomization approach, with the aim of identifying potential microbial characteristics associated with IVDD.

Methods: Using the data from genome-wide association studies (GWAS) involving 412 gut microbiota species and 227,388 controls and 29,508 cases of IVDD. Inverse variance weighted (IVW) was used as the primary Mendelian randomization (MR) analysis, complemented by weighted median, MR-Egger regression, weighted mode and simple mode methods. Extensive sensitivity analyses were performed to confirm the robustness of the results and to assess heterogeneity and horizontal pleiotropy.

Results: This study revealed a positive genetic predisposition between 6 types of gut microbiota and IVDD through the IVW method, indicating that increased levels of these microbiota may lead to a higher risk of IVDD. Conversely, 6 types of gut microbiota were found to have negative effects on IVDD, suggesting that increased levels of these microbiota may have a protective effect against IVDD. Reverse MR analysis results revealed such possibilities as 1 positive and 5 negative causal relationships between IVDD and gut microbiota. The results of Cochran's Q test, MR-Egger regression, and MR-PRESSO analysis from the bidirectional Mendelian randomization all yielded p-values greater than 0.05, indicating that there is no significant heterogeneity or pleiotropy in the genetic effect analysis between gut microbiota and IVDD.

Conclusion: We used a bidirectional Mendelian randomization approach to identify various gut microbiota associated with IVDD. Our findings lay the foundation for further exploration of the pathogenesis and treatment strategies of gut microbiota and IVDD, and provide new possibilities for research on biomarkers of IVDD-related metabolic microbiota.

Keywords: Genetic inference; Genome-wide association study; Gut microbiota; Intervertebral disc degeneration; Mendelian randomization.