Deciphering the causal links between gut microbiota and osteoporosis via two-sample Mendelian randomization

JOURNAL/agad/04.03/02274129-990000000-00014/figure1/v/2025-07-29T163611Z/r/image-tiff The relationship between gut microbiota and osteoporosis has garnered significant attention in recent years. However, comprehensive evidence supporting this relationship remains elusive. This study included a total of 211 species of gut microbiota to explore associations with osteoporosis and bone mineral density at various ages. A two-sample Mendelian randomization (MR) study was conducted to assess the associations between gut microbiota and osteoporosis. Data for 211 gut microbiota and osteoporosis cases were sourced from Genome-Wide Association Studies (GWAS). The inverse-variance weighted method with fixed effects, a commonly used Mendelian randomization approach, served as the primary verification method and was applied in the two-sample Mendelian randomization analysis. We employed mean pleiotropy of genetic variation and sensitivity analyses, with Mendelian randomization-Egger tests and the leave-one-out method as core evaluation techniques. Our study showed that 33 species of the gut microbiota were associated with the development of osteoporosis; among them, 6 species of the gut microbiota were directly related to the occurrence of osteoporosis. Additionally, over 33 species of gut microbiota were found to be related to bone mineral density. Our findings revealed that 33 species of the gut microbiota had varying degrees of impact on our research objectives, among which 6 species of the gut microbiota were directly related to the occurrence of osteoporosis. Most of these microbiota may influence bone health through mechanisms such as lipid metabolism, calcium level regulation, and mental state adjustment. Therefore, we believe that the gut microbiota is closely related to osteoporosis.