Genetic analysis of the causal relationship between gut microbiota and intervertebral disc degeneration: a two-sample Mendelian randomized study

Eur Spine J. 2023 Dec 13. doi: 10.1007/s00586-023-08059-8. Online ahead of print.

Abstract

Purpose: Several recent studies have reported a possible association between gut microbiota and intervertebral disc degeneration; however, no studies have shown a causal relationship between gut microbiota and disc degeneration. This study was dedicated to investigate the causal relationship between the gut microbiota and intervertebral disc degeneration and the presence of potentially bacterial traits using two-sample Mendelian randomization.

Methods: A two-sample Mendelian randomization study was performed using the summary statistics of the gut microbiota from the largest available genome-wide association study meta-analysis conducted by the MiBioGen consortium. Summary statistics of intervertebral disc degeneration were obtained from the FinnGen consortium R8 release data. Five basic methods and MR-PRESSO were used to examine causal associations. The results of the study were used to examine the causal association between gut microbiota and intervertebral disc degeneration. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables.

Results: By using Mendelian randomization analysis, 10 bacterial traits potentially associated with intervertebral disc degeneration were identified: genus Eubacterium coprostanoligenes group, genus Lachnoclostridium, unknown genus id.2755, genus Marvinbryantia, genus Ruminococcaceae UCG003, family Rhodospirillaceae, unknown genus id.959, order Rhodospirillales, genus Lachnospiraceae NK4A136 grou, genus Eubacterium brachy group.

Conclusion: This Mendelian Randomization study found a causal effect between 10 gut microbiota and intervertebral disc degeneration, and we summarize the possible mechanisms of action in the context of existing studies. However, additional research is essential to fully understand the contribution of genetic factors to the dynamics of gut microbiota and its impact on disc degeneration.

Keywords: Causal inference; Gut microbiota; Gut-disc axis; Intervertebral disc degeneration; Mendelian randomization.