Short chain fatty acids (SCFAs), including acetate, propionate, and butyrate, are major metabolic products of anaerobic bacterial fermentation in the intestine. These fatty acids serve as energy sources for intestinal epithelial cells and modulate various processes in the gastrointestinal tract, including electrolyte and water absorption. SCFAs are recognized as mediators that influence gut microbiota's effects on intestinal immune function. They act on leukocytes and endothelial cells through mechanisms such as activation of GPCRs (GPR41 and GPR43) and inhibition of histone deacetylase (HDAC). SCFAs regulate leukocyte functions, including cytokine production, eicosanoid synthesis, and chemokine secretion. They also affect leukocyte migration to inflammatory sites and pathogen destruction. SCFAs modulate leukocyte recruitment and activation by influencing chemotaxis, chemokine production, and adhesion molecule expression. For example, SCFAs induce neutrophil chemotaxis via GPR43 activation, while also reducing the expression of chemokine receptors. Butyrate inhibits macrophage migration and reduces the production of pro-inflammatory cytokines like MCP-1. SCFAs also modulate inflammatory mediator production by immune cells, including TNF-α, IL-6, and NO, and can suppress the production of pro-inflammatory mediators. Additionally, SCFAs affect the function of immune cells such as T cells and macrophages by modulating signaling pathways and gene expression. SCFAs have anti-inflammatory effects by inhibiting NF-κB and PPARγ activities, reducing adhesion molecule expression, and suppressing inflammatory responses. However, they can also have pro-inflammatory effects under certain conditions, such as promoting neutrophil migration in sites of anaerobic bacterial infection. SCFAs modulate phagocytic activity and reactive oxygen species (ROS) production in phagocytes, which is important in anaerobic bacterial infections. They also influence lymphocyte activation and response by modulating T-cell proliferation, cytokine production, and regulatory T cell function. In therapeutic applications, SCFAs have shown potential in treating inflammatory conditions such as inflammatory bowel disease (IBD), sepsis, and stroke. Studies indicate that SCFAs, particularly butyrate, can reduce inflammation, improve tissue function, and protect against organ damage. However, the precise mechanisms and optimal therapeutic applications of SCFAs require further investigation. Overall, SCFAs play a complex role in regulating inflammation and immune responses, with both anti-inflammatory and pro-inflammatory effects depending on the context and cell type involved.Short chain fatty acids (SCFAs), including acetate, propionate, and butyrate, are major metabolic products of anaerobic bacterial fermentation in the intestine. These fatty acids serve as energy sources for intestinal epithelial cells and modulate various processes in the gastrointestinal tract, including electrolyte and water absorption. SCFAs are recognized as mediators that influence gut microbiota's effects on intestinal immune function. They act on leukocytes and endothelial cells through mechanisms such as activation of GPCRs (GPR41 and GPR43) and inhibition of histone deacetylase (HDAC). SCFAs regulate leukocyte functions, including cytokine production, eicosanoid synthesis, and chemokine secretion. They also affect leukocyte migration to inflammatory sites and pathogen destruction. SCFAs modulate leukocyte recruitment and activation by influencing chemotaxis, chemokine production, and adhesion molecule expression. For example, SCFAs induce neutrophil chemotaxis via GPR43 activation, while also reducing the expression of chemokine receptors. Butyrate inhibits macrophage migration and reduces the production of pro-inflammatory cytokines like MCP-1. SCFAs also modulate inflammatory mediator production by immune cells, including TNF-α, IL-6, and NO, and can suppress the production of pro-inflammatory mediators. Additionally, SCFAs affect the function of immune cells such as T cells and macrophages by modulating signaling pathways and gene expression. SCFAs have anti-inflammatory effects by inhibiting NF-κB and PPARγ activities, reducing adhesion molecule expression, and suppressing inflammatory responses. However, they can also have pro-inflammatory effects under certain conditions, such as promoting neutrophil migration in sites of anaerobic bacterial infection. SCFAs modulate phagocytic activity and reactive oxygen species (ROS) production in phagocytes, which is important in anaerobic bacterial infections. They also influence lymphocyte activation and response by modulating T-cell proliferation, cytokine production, and regulatory T cell function. In therapeutic applications, SCFAs have shown potential in treating inflammatory conditions such as inflammatory bowel disease (IBD), sepsis, and stroke. Studies indicate that SCFAs, particularly butyrate, can reduce inflammation, improve tissue function, and protect against organ damage. However, the precise mechanisms and optimal therapeutic applications of SCFAs require further investigation. Overall, SCFAs play a complex role in regulating inflammation and immune responses, with both anti-inflammatory and pro-inflammatory effects depending on the context and cell type involved.