Role of short chain fatty acids in gut health and possible therapeutic approaches in inflammatory bowel diseases

Figure 2 Short-chain fatty receptors and intracellular signaling. Short-chain fatty acids (SCFAs) binds to G-protein coupled receptors such as GPR41 and GPR43 receptors also known as free fatty acid receptors (FFAR) 3 and FFAR2, respectively. The activation of GPR41 and GPR43 receptors through G_i subunit promotes inhibition of adenylate cyclase which inhibit cyclic adenosine monophosphate (cAMP) that inhibit protein kinase A. GPR43 receptor activation through G_q subunit promotes activation of phospholipase C which activate inositol 1,4,5-trisphosphate (IP₃) leading to the elevation of intracellular calcium levels. GPR43 receptor activation through G_q subunit also promotes activation of phospholipase C which activate protein kinase C leading to activation of extracellular signal-regulated kinase 1/2 (ERK1/2) cascade. The activation of these receptors inhibits translocation of nuclear factor kappa B (NF- ΚB), altering the expression of certain proteins, promotes an increase in the release of gut hormones such as Peptide YY (PYY) and Glucagon-like peptide 1 (GLP-1), increase intestinal barrier integrity and Transepithelial Electrical Resistance (TEER), reduce pro-inflammatory markers levels, and increase anti-inflammatory markers levels. The authors have obtained the permission for figure using from the BioRender.com (Supplementary material).