Evaluation of causal links of gut microbiota and inflammatory cytokines with 10 fracture locations: A Mendelian randomization study

Recent investigations have revealed an association of variations in gut microbiota (GM) composition and inflammatory cytokine (IC) levels with fracture risk; however, the causal relationship of GM or inflammatory factors with fracture risk remains unelucidated. The study utilized Mendelian randomization (MR) analyses, utilizing aggregated data from the genome-wide association study of GM, ICs, and 10 fracture locations. The primary aim was to examine the causal associations between GM, ICs, and 10 fracture locations. Furthermore, mediational analyses and multivariate MR were conducted to explore the potential mediating role of ICs in this relationship. MR analysis identified 35 positive and 53 negative causal associations between GM and 10 fracture locations. ICs showed 22 positive and 24 negative correlations with 10 fracture locations. However, after false discovery rate correction, most associations lost significance, leaving only 1 IC significant for foot fractures. Moreover, our findings suggest that the ICs may be act as a mediating factor in the pathway from GM to 10 fracture locations. GM and ICs exhibited a significant causal relationship with the 10 fracture locations; furthermore, ICs may function as mediators in the pathway from GM to fracture risk.