The causal relationship between gut microbiota and 2 neoplasms, malignant and benign neoplasms of bone and articular cartilage: A two-sample Mendelian randomization study.

Abstract

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 2 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. In this study, single nucleotide polymorphisms (SNPs) from genome-wide association studies-pooled data related to bone neoplasms and gut microbiota abundance were evaluated. The inverse variance weighted was employed as the major method for assessing the aforementioned causal relationship. Furthermore, the horizontal multiplicity was evaluated utilizing the Mendelian randomization pleiotropy residual sum and outlier and the MR-Egger intercept test. Finally, inverse MR analysis was performed to assess reverse causality. Inverse variance weighted 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 = .01), Odoribacter (OR = 0.23, 95% CI = 0.06-0.84, P = .03), Slackia (OR = 0.35, 95% CI = 0.13-0.93, P = .04), and Tyzzerella3 (OR = 0.44, 95% CI = 0.24-0.82, P = .01) exhibited a protective effect against MNBAC. On the other hand, of the 3 gut microbes identified as potentially causally related to BNBAC, Oscillibacter (OR = 0.79, 95% CI = 0.63-0.98, P = .03) and Ruminococcus torques group (OR = 0.62, 95% CI = 0.39-0.98, P = .04) were regarded as protective strains of B, while Eubacterium ruminantium group (OR = 1.24, 95% CI = 1.04-1.47, P = .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. Four gut microbiota showed causal effects on MNBAC, and 3 gut microbiota demonstrated causality in BNBAC, providing insights into the design of future interventions to reduce the burden of neoplasms.