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Recent studies demonstrate that SCFAs affect bone metabolism via the processes outlined ( Figure 2 ): Intestinal Epithelial Function and Mineral Absorption: SCFAs act on IECs to promote their development and differentiation, hence affecting the mechanical, chemical, immune, and biological barriers of the intestinal mucosa, regulating electrolyte exchange (such as between mineral ions and hydrogen ions), lowering luminal pH, and directly improving the absorption of minerals specially calcium (99, 100);Systemic Signaling via G protein-coupled receptors (GPCRs): Upon entering systemic circulation, SCFAs interact with GPCRs, influencing metabolism and function in peripheral tissues, including adipose tissue, skeletal muscle, bone, and liver (101);Epigenetic Regulation: SCFAs block histone deacetylases (HDACs), therefore contributing to the epigenetic regulation of gene expression, which may influence bone metabolism (102, 103);Modulation of Inflammatory Cytokines: SCFAs can modulate the production of inflammatory factors, therefore affecting bone remodeling (54);Immune Cell Regulation: SCFAs facilitate the development of regulatory T (Treg) cells and trigger death in macrophages and neutrophils

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