Figure 3.

Graphical representation of presumed immunomodulatory effects of butyrate in the periphery and the CNS. MCT-1 receptors are widely distributed across the BBB and CNS cells, such as astrocytes, neurons, and oligodendrocytes, while MCT-2 is primarily located on neurons [56]. MCT-2 exclusively transports butyrate. Butyrate functions as an energy source for MCT-1 in a sodium-dependent manner. Prolonged exposure to butyrate promotes MCT-1 expression via NF-kB and enhances the stability of MCT-1 gene regulation through mRNA [43,44]. Additionally, butyrate acts as HDAC-I on oligodendrocytes, promoting remyelination. At the BBB level, butyrate activates AMPK, which, in turn, upregulates the assembly of TJ. In the periphery, butyrate acts as a Foxp3+ promoter that subsequently induces CD4+ T cell differentiation to a Treg lineage. It also interacts with GPCRs, such as GPR41 and GPR109A, found on the surface of peripheral blood mononuclear cells. Upregulation of GPR109A induces Treg expression and IL-10 secretion. T lymphocytes lack GPCRs that bind to butyrate or any other SCFA; therefore, T lymphocyte modulation is triggered by HDAC-I. Butyrate also supports the synthesis and assembly of TJ [43,69,70].