Tributyrin, also known as glyceryl tributyrate, is a triacylglycerol (TAG) consisting of three butyric acid (C4:0) chains esterified to a glycerol backbone, serving as a prodrug for sustained butyrate release in biological systems. This short-chain TAG occurs naturally in butter and dairy products and has gained increasing attention for its roles in gut health, anti-inflammatory activity, and cancer research.
Chemical Structure
Tributyrin has the molecular formula C15H26O6 and a molecular weight of 302.4 g/mol. Its symmetric structure—where glycerol is esterified at the sn-1, sn-2, and sn-3 positions with butanoyl chains—confers high susceptibility to hydrolysis by pancreatic and microbial lipases, leading to the progressive release of butyrate, dibutyrylglycerol, and monobutyrylglycerol.
Physical Properties
Tributyrin is a colorless, oily liquid with a density of approximately 1.03 g/cm³, a boiling point of 305 °C, a melting point of −75 °C, and a refractive index of 1.435. It exhibits low miscibility with water (log WS −2.8) but is soluble in organic solvents such as ethanol and chloroform. Its vapor pressure (0.0007 mmHg at 25 °C) and flash point (170 °C) indicate suitable physicochemical stability for oral formulation and delivery.
Biological Functions
Following hydrolysis by butyric esterases in colonocytes, tributyrin increases local butyrate concentrations, thereby providing metabolic fuel for epithelial cells, inhibiting histone deacetylases (HDACs), and modulating gene expression associated with epithelial barrier integrity and anti-tumor activity. Unlike free butyrate, tributyrin can bypass degradation in the upper gastrointestinal tract. It has also been shown to restore microbiota balance, reduce inflammation through activation of GPR43, and suppress NF-κB signaling pathways in experimental models of inflammatory bowel disease.
