Gut microbiota and intervertebral disc degeneration: a bidirectional two-sample Mendelian randomization study

Abstract

Background Although previous studies have suggested a close association between gut microbiota (GM) and intervertebral disc degeneration (IVDD), the causal relationship between them remains unclear. Hence, we thoroughly investigate their causal relationship by means of a two-sample Mendelian randomization (MR) study, aiming to determine the impact of gut microbiota on the risk of developing intervertebral disc degeneration. Methods Summary data from genome-wide association studies of GM (the MiBioGen) and IVDD (the FinnGen biobank) have been acquired. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach. Weighted median, MR-Egger regression, weighted mode, and simple mode were used as supplements. The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were performed to assess horizontal pleiotropy. Cochran's Q test evaluated heterogeneity. Leave-one-out sensitivity analysis was further conducted to determine the reliability of the causal relationship. A reverse MR analysis was conducted to assess potential reverse causation. Results We identified nine gut microbial taxa that were causally associated with IVDD (P < 0.05). Following the Benjamini–Hochberg corrected test, the association between the phylum Bacteroidetes and a higher risk of IVDD remained significant (IVW FDR-corrected P = 0.0365). The results of the Cochrane Q test did not indicate heterogeneity (P > 0.05). Additionally, both the MR-Egger intercept test and the MR-PRESSO global test revealed that our results were not influenced by horizontal pleiotropy (P > 0.05). Furthermore, the leave-one-out analysis substantiated the reliability of the causal relationship. In the reverse analysis, no evidence was found to suggest that IVDD has an impact on the gut microbiota. Conclusion Our results validate the potential causal impact of particular GM taxa on IVDD, thus providing fresh insights into the gut microbiota-mediated mechanism of IVDD and laying the groundwork for further research into targeted preventive measures.

Gut microbiota and radiculopathy: a bidirectional two-sample Mendelian randomization study

“…Radiculopathy are mainly caused by chronic compression or infringement of nerve roots, with major contributing factors including ectopic ossi cation leading to bone spur formation, spinal canal stenosis, disc protrusion compression, osteoporosis, and local in ammation. Magnetic Resonance (MR) analysis of the gut microbiota and intervertebral disc degeneration shows that the presence of the Marvinbryantia microbial group is an important risk factor for intervertebral disc degeneration, consistent with our research results [3]. Currently, the in uence of gut microbiota on osteoporosis and intervertebral disc lesions has been elucidated, which may be an indirect in uencing factor for the occurrence of radiculopathy [14][15].…”

“…These bacteria have also been linked to the development of various diseases, highlighting their signi cance in maintaining overall health. Recent studies have reported a causal relationship between gut microbes and disc degeneration as well as other spinal degenerative diseases [2][3][4]. Although it has been reported in the literature that it is associated with radiculopathy, the causal relationship has not been clari ed.…”

Roles of organokines in intervertebral disc homeostasis and degeneration

“…In recent years, the interplay between the digestive system and disc homeostasis has received increasing attention, with a special focus on the role of the gut microbiota in the gastrointestinal endocrine system (150)(151)(152)(153). It is worth noting that the endocrine functions of the digestive system facilitate complex inter-organ communication through various gastrointestinal hormones (such as Ghrelin and Amylin) and hepatokines (Figure 4, Table 3) (154,155).…”