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Particularly, the gut pH tremendously affects the concentration of butyrate because of differing tolerance to low pH of the major bacterial functional groups that comprise the human colonic microbiota ( 2.4 Butyrate absorption Butyrate is mainly considered be absorbed via active transport mediated by monocarboxylate transporters (MCTs) ( via MCTs is very little, because the magnitude of the transmembrane H+ gradient across the colonocyte apical membrane is puny ( 2.5 Butyrate distribution Up to 95% of butyrate produced by the gut microbiota is absorbed and used in colonocytes and only a very small part is absorbed into the circulation ( via the hepatic portal vein, which connects the gastrointestinal tract, spleen and liver ( 11 C-labeled butyric acid in baboons found relatively high accumulation of the label in the spleen, and pancreas ( 13 C-labeled butyrate in the intestine, brain, brown adipose tissue (BAT), white adipose tissue (WAT), and especially the brain ( Clostridium butyricum ( 2.6 Butyrate metabolism and excretion Butyrate is predominantly metabolized in the colon as an energy substrate, with small concentrations utilized by the liver and kidneys, providing up to 70% of the energy needs of colon cells, and the amount of butyrate metabolized was followed by the excretion of CO 2 in breath ( 3 Cellular signaling pathways of butyrate 3.1 G protein-coupled receptors (GPCRs) Butyrate is the ligand for metabolite-sensing G-protein coupled receptors (GPCRs), mainly GPR43, GPR41, and GPR109a ( 3.2 Histone deacetylases (HDACs) Butyrate is also a histone deacetylase inhibitor (HDACi)

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