Biological effects / Functions & Butyrate / Butyric acid

Butyrate has dual roles in normal and tumor colonocytes. In normal cells, it serves as an energy source, metabolized to acetyl-CoA in the Krebs cycle, promoting cell proliferation. In tumor cells, due to the Warburg effect, butyrate does not enter the Krebs cycle but instead modulates gene expression through HDAC inhibition, leading to downregulation of Cyclin-dependent kinase inhibitor 1 (p21Cip1/Waf1) and Cyclin-dependent kinase inhibitor 1B (p27Kip1), inhibiting cell proliferation, and providing cancer-related benefits
Hanus et al. 2021

Butyrate is taken up by e.g., colonocytes and converted into butyryl-CoA, then into acetyl-CoA. Acetyl-CoA is a key substrate for the Krebs cycle, where it fuels cellular respiration for ATP production. This conversion ties butyrate directly into energy metabolism via the TCA cycle. It is not available to the nucleus.
Hanus et al. 2021

Butyrate is the preferred energy source for colon epithelial cells, and its deficiency may impair gastrointestinal function
Riviere et al. 2016 Front. Microbiol. 7: 979
Blaak et al. 2020 Benefic. Microbes 11: 411-455

G-Protein Coupled Receptor 41 (GPR41) is expressed in intestinal Enteroendocrine Cells (EEC), stimulating the release of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). PYY can regulate intestinal movement, affecting the absorption of nutrients in the intestine, and GLP-1 can regulate satiety.
Li et al. 2020s

Butyrate facilitates the maturation of the colonic mucus barrier and counteracts the growth of pathobionts
Zegarra-Ruiz et al. 2019 Cell Host Microbe 25: 113-127.e6
Beaumont et al. 2020 Gut Microbes 11: 1268-1286

Butyrate is linked to numerous health benefits. It provides energy to colonocytes.
Fu et al. 2019 Critical Reviews in Food Science and Nutrition 59: S130-S152

Butyrate activates PPAR-gamma Signal transduction in human epithelial cells (Alex et al. 2013 Mol. Cell. Biol. 33: 1303) to drive the metabolism of surface colonocytes toward mitochondrial beta-oxidation (Duszka et al. 2017 Int. J. Mol. Sci. 18: 2559; 36-37), which is essential for maintaining physiologic hypoxia
Byndloss et al., 2017 Science 357: 570

Increased butyrate in humans is associated with improved glucose tolerance. In a clinical trial, individuals on a high-fiber diet showed increased butyrate levels and lower Hemoglobin A1c, which is a measure of blood glucose control
Qin et al. 2012 Nature 490: 55-60
Zhao et al. 2018 Science 359: 1151-1156
Sanna et al. 2019 Nat Genet. 51(4): 600-605

Butyrate also appears to ameliorate insulin sensitivity by stimulating the secretion of glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP)) incretins. Butyrate enhances the expression of the anorexigenic adipokine leptin
Nobili et al. 2019 Adv Exp Med Biol 1125: 85-100

Butyrate suppresses intestinal inflammation and oxidative stress, while protecting the intestinal epithelial barrier via its HDAC inhibitor role
Han et al. 2018a

Butyrate / Butyric acid is considered to be anti-carcinogenic and anti-inflammatory.
van der Beek et al. 2017 Nutr. Rev. 75: 286-305

Mechanistic studies in animal models showed beneficial effects of Butyrate / Butyric acid in maintaining GI barrier integrity, quenching oxygen at the epithelial interface, and exerting immune-modulating effects.
Arpaia et al. 2013 Nature 504: 451-455
Rivera-Chávez et al. 2016 Cell Host Microbe 19: 443

Butyrate blocks dendritic cell generation. They don't affect granulocytes. This depends on the transporter Sodium-Coupled Monocarboxylate Transporter 1 (SMCT1). It moves butyrate into cells. These metabolites inhibit histone deacetylases.
Singh et al. 2010 Journal of Biological Chemistry. 285:27601-27608

Butyrate is known to be a primary energy source for colonocytes
Cummings et al. 1987 Gut 28: 1221-1227
Al-Lahham et al. 2010 Biochimica et Biophysica Acta 1801: 1175-1183

Butyrate, but not acetate or propionate, inhibited lymphocyte proliferation and IL-2 production in rats
Cavaglieri et al. 2003

see also:
Biological effects / Functions & Short-Chain Fatty Acids (SCFAs)
Butyrate / Butyric acid & Cancer / Tumors
Butyrate / Butyric acid & Dendritic cells (DCs)
Butyrate / Butyric acid & Histone deacetylases (HDACs)
Butyrate / Butyric acid & Histone Deacetylase (HDAC) inhibition
Butyrate / Butyric acid & Colitis / Intestinal inflammation
Butyrate / Butyric acid & Lipogenesis
Butyrate / Butyric acid & Sodium-Coupled Monocarboxylate Transporter 1 (SMCT1)
Butyrate-producing bacteria
Energy Source & Short-Chain Fatty Acids (SCFAs)
Gut microbiota & Type 2 Diabetes (T2D)
Gut microbiota & Metabolic diseases / Metabolic disorders
Short-chain Fatty Acids (SCFAs) & Type 2 Diabetes (T2D)