butyrate

Butyrate, or butanoic acid, is a four-carbon short-chain fatty acid that is a major product of anaerobic fermentation of dietary fiber by gut microbiota. In the colon it exists both as the undissociated acid and as salts such as sodium butyrate, depending on local pH.

Butyrate is primarily produced in the large intestine by bacterial fermentation of complex carbohydrates. Key butyrate-producing bacteria include Faecalibacterium prausnitzii, Roseburia species, and Eubacterium rectale. Dietary fibers such as resistant starch, inulin, and pectin promote its generation. Luminal concentrations of butyrate commonly reach several millimolar, and the compound is a major energy source for colonocytes.

Physiologically, butyrate supports intestinal health through multiple mechanisms. It serves as the main energy source for colonocytes and helps maintain epithelial barrier integrity. It also exerts anti-inflammatory effects and modulates immune function. At the molecular level, butyrate acts as an inhibitor of histone deacetylases, influencing gene expression and epigenetic regulation. It also signals through G-protein coupled receptors, including GPR41 (FFAR3), GPR43 (FFAR2), and GPR109A, affecting lipid metabolism, insulin sensitivity, and inflammatory responses.

Clinically, reduced butyrate production has been associated with disorders such as inflammatory bowel disease and may influence colorectal cancer risk. Increasing dietary fiber intake or using butyrate-producing probiotics can raise luminal butyrate levels, though direct therapeutic use of butyrate or its salts is primarily supportive and subject to ongoing research. Its chemical properties include a four-carbon chain with a pKa around 4.8, and it is absorbed by colonocytes via monocarboxylate transporters.