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SCFA reduces Bacterial Translocation / Intestinal permeability and reduces inflammation
Inflammation downregulates Short-chain Fatty Acids (SCFAs) transporters, reducing colonocyte uptake and systemic circulation of Short-chain Fatty Acids (SCFAs)
Loss of O. splachnicus results in reduced SCFAs availability, leading to host inflammation
Fatty acid oxidation and oxidative phosphorylation are typically the “anti-inflammatory immune-metabolic pathways” fuelling Treg and antiinflammatory macrophages (M2)
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Acetate and butyrate stimulate GPR43 receptors and, additionally, butyrate stimulates specifically G-Protein Coupled Receptor 109a (GPR109a), also known as niacin receptors 1 (NIACR1), located on the colonic Enterocytes / Intestinal Epithelial Cells (IECs) membranes.
The interactions result in intracellular Ca2+ release, K+ efflux stimulation, and membrane hyperpolarization leading to NLRP3 inflammasome activation.
Interleukin-18 (IL-18) belongs to the IL-1 family of pro-inflammatory cytokines and is released
Intestinal epithelial cells (IECs) absorb short-chain fatty acids (SCFAs) through passive means, primarily in their non-ionized form, as well as through active mechanisms mediated by Slc16a1 and Slc5a8. Once inside the nucleus, SCFAs lead to an increase in Retinaldehyde dehydrogenase 1 (RALDH1) by inhibiting histone deacetylases Histone deacetylase 1 (HDAC1) and Histone deacetylase 3 (HDAC3). Of the various SCFA species, butyrate is particularly notable for its potent inhibitory effect on histone deacetylases, especially HDAC3.
The hyperacetylation of DNA histones, especially histone H3 acetylation (Davie et al. 2003 J Nutr 133 (7, Suppl):2485S–2493S), results in the inhibition of the proinflammatory transcription factor NF kappa B (NFKB) / NFKB Family, which in turn causes anti-inflammatory activities.
Short-chain Fatty Acids (SCFAs) stimulate the maturation of gut-associated immune cells with anti-inflammatory potential
Acetate, butyrate, and propionate pass through the IEC layer into the lamina propria. There they meet neutrophils, Group 3 ILCs (ILC3), macrophages, Dendritic Cells (DCs), T cells / T lymphocytes, and B cells / B Lymphocytes
see also:
Anti-inflammatory Activity / Anti-inflammatory Responses & Short-chain fatty acids (SCFAs)
Butyrate / Butyric acid & G-Protein Coupled Receptor 109a (GPR109a)
Butyrate / Butyric acid & Histone acetylation / Histone acetyltransferase (HAT)
Colitis / Intestinal Inflammation & Short-Chain Fatty Acids (SCFAs)
G-Protein Coupled Receptors (GPCRs) & Short-Chain Fatty Acids (SCFAs)
Inflammasomes & Short-chain fatty acids (SCFAs)