SCFAs have been shown to induce the extrathymic differentiation of Tregs, also known as pTregs, via GPCR activation and HDAC inhibition.16,25,62,65,66 Acetate promotes pTreg by inhibiting HDAC9 to enhance acetylation at Foxp3.67 Butyrate treatment is suggested to promote colonic Treg differentiation and mitigates colitis by enhancing histone H3 acetylation at the Foxp3 locus, and the process is independent of GPR43.65 In fact, the effect of butyrate on Treg differentiation is context-dependent, requiring the presence of transforming growth factor-β (TGF-β). This evidence concerns the gene FOXP3 and colitis.