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Uncovering the Relationship between Gut Microbiota, Neurophysiological States and Bone Diseases

Abstract

Zhiyang Yufan

Elevating evidence underscores a strong connection between gut microbiota and bone diseases, yet the presence of a definitive causal link between them remains elusive. In this investigation, we conducted a comprehensive examination of the association between gut microbiota and skeletal disorders utilizing genome-wide association studies. We employed linkage disequilibrium score regression and Mendelian randomization to delve into genetic causation. Additionally, we explored the possible intermediary role of neuropsychological states, such as cognition, depression, and insomnia, in the relationship between gut microbiota and bone diseases through mediation analysis. Genetic colocalization analysis was employed to identify potential targets. Our findings point to a direct causal connection between Ruminococcaceae and knee Osteoarthritis (OA), with this association seemingly influenced by cognitive performance and insomnia. Likewise, we observed a causal link between Burkholderiales and lumbar pelvic fractures, mediated by cognitive performance. Colocalization analysis revealed a shared causal variant (rs2352974) at the TRAF-interacting protein locus, impacting both cognitive ability and knee OA. This study presents compelling evidence that modifications in gut microbiota may enhance cognitive abilities, alleviate insomnia, and potentially reduce the risk of site-specific fractures and OA. Consequently, strategies aimed at optimizing gut microbiota could represent innovative and efficacious preventive measures against fractures and OA.