Microbiota metabolites in bone: Shaping health and Confronting disease

The intricate interplay between the gut microbiota and bone health has become increasingly recognized as a fundamental determinant of skeletal well-being. Microbiota-derived metabolites play a crucial role in dynamic interaction, specifically in bone homeostasis. In this sense, shortchain fatty acids (SCFAs), including acetate, propionate, and butyrate, indirectly promote bone formation by regulating insulin-like growth factor-1 (IGF-1). Trimethylamine N-oxide (TMAO) has been found to increase the expression of osteoblast genes, such as Runt-related transcription factor 2 (RUNX2) and bone morphogenetic protein-2 (BMP2), thus enhancing osteogenic differentiation and bone quality through BMP/SMADs and Wnt signaling pathways. Remarkably, in the context of bone infections, the role of microbiota metabolites in immune modulation and host defense mechanisms potentially affects susceptibility to infections such as osteomyelitis. Furthermore, ongoing research elucidates the precise mechanisms through which microbiotaderived metabolites influence bone cells, such as osteoblasts and osteoclasts. Understanding the multifaceted influence of microbiota metabolites on bone, from regulating homeostasis to modulating susceptibility to infections, has the potential to revolutionize our approach to bone health and disease management. This review offers a comprehensive exploration of this evolving field, providing a holistic perspective on the impact of microbiota metabolites on bone health and diseases.