The causal relationship between gut microbiota and two neoplasms, malignant and benign neoplasms of bone and articular cartilage: a two-sample mendelian randomization study

Abstract

Abstract Background Previous research has demonstrated a close connection between the development of bone neoplasms and variations in the abundance of specific gut microbiota. It remains unclear, however, how the gut microbiota and bone neoplasms are causally related. Hence, in our study, we aim to clarify this relationship between gut microbiota and two neoplasms, malignant neoplasm of bone and articular cartilage (MNBAC) and benign neoplasm of bone and articular cartilage (BNBAC), by employing a two-sample Mendelian randomization (MR) approach. Methods In this study, single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS)-pooled data related to bone neoplasms and gut microbiota abundance were evaluated. The inverse variance weighted (IVW) was employed as the major method for assessing the aforementioned causal relationship, while the weighted median, MR-Egger, weighted mode, and simple mode were employed as complementary methods. Furthermore, the horizontal multiplicity was evaluated utilizing the mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and the MR-Egger intercept test. Cochran's Q test to evaluate heterogeneity and “leave-one-out” sensitivity analysis to determine the reliability of causality. Finally, inverse MR analysis was performed to assess reverse causality. Results IVW results indicate a potential genetic relationship between 4 gut microbiota and MNBAC, and 3 gut microbiota and BNBAC. On the one hand, Eubacterium eligens group (OR = 0.16, 95% CI = 0.04–0.67, P = 0.01), Odoribacter (OR = 0.23, 95% CI = 0.06–0.84, P = 0.03), Slackia (OR = 0.35, 95% CI = 0.13–0.93, P = 0.04), and Tyzzerella3 (OR = 0.44, 95% CI = 0.24–0.82, P = 0.01) exhibited a protective effect against MNBAC. On the other hand, of the three gut microbes identified as potentially causally related to BNBAC, Oscillibacter (OR = 0.79, 95% CI = 0.63–0.98, P = 0.03) and Ruminococcustorques group (OR = 0.62, 95% CI = 0.39–0.98, P = 0.04) were regarded as protective strains of B, while Eubacterium ruminantium group (OR = 1.24, 95% CI = 1.04–1.47, P = 0.02) was considered to be a risk factor for increasing the incidence of BNBAC. Additionally, the bone neoplasms were not found to have a reverse causal relationship with the above 7 gut microbiota taxa. No heterogeneity or horizontal pleiotropy was identified in this study. Conclusion The causal relationship between the gut microbiota and two neoplasms, MNBAC and BNBAC, was revealed in this two-sample MR study. Of course, further research needs to be conducted to verify the above findings.