This narrative review explores how multi-omics approaches, including metagenomics and metabolomics, help explain connections between the gut microbiome and bone health. The authors examined data involving osteoporosis, osteoarthritis, and bone malignancies to understand these complex interactions. No specific patient groups or sample sizes were reported in this review.
The study highlights several key mechanisms. Short-chain fatty acids were found to inhibit osteoclastogenesis via GPR43 and HDAC signaling. Additionally, these fatty acids promote osteoblast metabolic reprogramming. Bile acids were shown to enhance osteogenesis through FXR and Wnt signaling pathways. Tryptophan metabolites also play a role by repairing intestinal barrier integrity and modulating osteoimmunity via the AhR pathway.
The review concludes that microbiome-driven immunometabolic reprogramming acts as a central regulator of skeletal homeostasis. This understanding could advance precision microbial therapeutics and chrono-nutritional strategies. However, the integration of multi-omics approaches to fully elucidate circadian metabolite-bone interactions remains limited. Readers should view these findings as a foundation for future research rather than immediate clinical solutions.