Navigating the gut-bone axis: The pivotal role of Coprococcus3 in osteoporosis prevention through Mendelian randomization

Abstract

Osteoporosis (OP) constitutes a notable public health concern that significantly impacts the skeletal health of the global aging population. Its prevalence is steadily escalating, yet the intricacies of its diagnosis and treatment remain challenging. Recent investigations have illuminated a profound interlink between gut microbiota (GM) and bone metabolism, thereby opening new avenues for probing the causal relationship between GM and OP. Employing Mendelian randomization (MR) as the investigative tool, this study delves into the causal rapport between 211 varieties of GM and OP. The data are culled from genome-wide association studies (GWAS) conducted by the MiBioGen consortium, in tandem with OP genetic data gleaned from the UK Biobank, BioBank Japan Project, and the FinnGen database. A comprehensive repertoire of statistical methodologies, encompassing inverse-variance weighting, weighted median, Simple mode, Weighted mode, and MR-Egger regression techniques, was adroitly harnessed for meticulous analysis. The discernment emerged that the genus Coprococcus3 is inversely associated with OP, potentially serving as a deterrent against its onset. Additionally, 21 other gut microbial species exhibited a positive correlation with OP, potentially accentuating its proclivity and progression. Subsequent to rigorous scrutiny via heterogeneity and sensitivity analyses, these findings corroborate the causal nexus between GM and OP. Facilitated by MR, this study successfully elucidates the causal underpinning binding GM and OP, thereby endowing invaluable insights for deeper exploration into the pivotal role of GM in the pathogenesis of OP.