ABSTRACT
Background: Emerging evidence from observational studies and clinical trials suggests a connection between the gut microbiota and variations in bone mineral density (BMD). Nonetheless, the specific association between gut microbiota and BMD alterations at different skeletal sites has not been comprehensively explored. To address this, we employed Genome-Wide Association Study (GWAS) summary statistics from a publicly accessible database, conducting a two-sample Mendelian Randomization analysis to elucidate the potential causal relationship between gut microbiota composition and BMD. Methods: This study utilized two distinct thresholds for screening instrumental variables (IVs), followed by an extensive series of quality control procedures to identify IVs that were significantly related to exposure. Gut microbiota were classified into two sets based on hierarchical levels: phylum, class, order, family, and genus. Bone mineral density (BMD) data were systematically collected from four skeletal sites: femoral neck, lumbar spine, forearm, and heel. For Mendelian Randomization (MR) analysis, robust methods including Inverse-Variance Weighting (IVW) and the Wald Ratio Test were employed. Additional analytical tests such as the Outlier Test, Heterogeneity Test, 'Leave-One-Out' Test, and Pleiotropy Test were conducted to assess the impact of horizontal pleiotropy, heterogeneities, and the genetic variation stability of gut microbiota on BMD causal associations. The MR Steiger Directionality Test was applied to exclude studies with potential directional biases. Results: In this two-sample Mendelian randomization analysis, we utilized five sets of exposure GWAS (Genome-Wide Association Studies) summary statistics and four sets of outcome GWAS summary statistics. The initial analysis, applying a threshold of p < 5 × 10-6, identified 48 significant causal relationships between genetic liability in the gut microbiome and bone mineral density (BMD). A subsequent analysis with a more stringent threshold of p < 5 × 10-8 uncovered 14 additional causal relationships. Upon applying the Bonferroni correction, 9 results from the first analysis and 10 from the second remained statistically significant. Conclusion: Our MR analysis revealed a causal relationship between gut microbiota and bone mineral density at all sites, which could lead to discoveries in future mechanistic and clinical studies of microbiota-associated osteoporosis.
ABSTRACT
Surveying the developmental history of the cognition and treatment of apoplexy in traditional Chinese medicine, it could be divided into 3 phases, viz. the phase of "exogenous wind" before the Tang and Song dynasties, the phase of contention of "endogenous wind" during the Jin, Yuan and Ming dynasties, and the phase of compromising of traditional Chinese and consulting of western medicine of "equal importance of exogenous and endogenous wind" after the Qing dynasty. Through the development of these three phases, the cognition of cause of disease and pathogenesis of apoplexy was deepened continuously, and the method of treatment, prescription and materia medica were enriched further. Especially, with the introduction and usage of modern scientific technology, the diagnosis and treatment of apoplexy were more standardized, and the effect was improved constantly, reflecting the characteristic and superiority of traditional Chinese medicine.
