Propionic acid (Propionate) (PPA)

Propionate, or propionic acid, is a three-carbon short-chain fatty acid (SCFA) primarily produced by the intestinal microbiota during the fermentation of dietary fibers. It serves as a vital signaling molecule that bridges the gut microbiome and host physiology by activating specific G protein-coupled receptors, namely Free Fatty Acid Receptor 2 (FFAR2/GPR43) and Free Fatty Acid Receptor 3 (FFAR3/GPR41). Propionate is involved in maintaining energy homeostasis by acting as a precursor for hepatic gluconeogenesis and regulating appetite through the stimulation of gut hormones like GLP-1 and PYY. It also exhibits potent anti-inflammatory effects by modulating immune cell activity and inhibiting histone deacetylases (HDACs). While beneficial at physiological levels, abnormal propionate content is associated with various pathologies; for instance, low levels are linked to obesity and inflammatory bowel disease, while excessive accumulation is a hallmark of the genetic disorder propionic acidemia, which leads to neurotoxicity and metabolic acidosis. Therapeutic strategies include the use of prebiotics like inulin to boost endogenous production and pharmacological agents like L-carnitine or antibiotics to manage toxic levels in metabolic disorders.

Other names

Propanoic acidPropionateC3Methylacetic acidEthanecarboxylic acid

Activation of G protein-coupled receptors (FFAR2/GPR43 and FFAR3/GPR41), inhibition of histone deacetylases (HDACs), and serving as a substrate for hepatic gluconeogenesis.