Propionic acid (PA) is a short chain fatty acid (SCFA) that is produced by bacterial (or gut) fermentation of fiber and sugars. The human skin is host of several species of bacteria known as Propionibacteria, which are named after their ability to produce propionic acid. The most notable one is the Propionibacterium acnes, which lives mainly in the sebaceous glands of the skin and is one of the principal causes of acne. Propionic acid can also play a role in carboxylic acid metabolism. In particular, propionyl coenzyme A (propionyl-CoA), is the first step in the process. Because propionic acid has three carbons (instead of two), propionyl-CoA cannot directly enter either beta oxidation or the citric acid cycles. In addition to its role in basic biochemistry, propionic acid is widely used as an antifungal agent in food. It is present naturally at low levels in dairy products and occurs ubiquitously, together with other short-chain fatty acids (SCFA), in the gastro-intestinal tract of humans and other mammals as an end-product of the microbial digestion of carbohydrates. It has significant physiological activity in animals. PA is a known irritant but produces no acute systemic effects and has no demonstrable genotoxic potential (PMID 1628870). When present in sufficiently high levels, propionic acid can act as an acidogen and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of propionic acid are associated with Propionic acidemia and aciduria. Propionic aciduria is one of the most frequent organic acidurias. Propionic acidemia is characterized almost immediately in newborns. Symptoms include poor feeding, vomiting, dehydration, acidosis, low muscle tone (hypotonia), seizures, and lethargy. Those who survive past infancy generally have poor intellectual development patterns, with 60% having an IQ less than 75 and requiring special education. Successful liver and/or renal transplantations, in a few patients, have resulted in better quality of life but have not prevented neurological and various visceral complications. Decreased early mortality, less severe symptoms at diagnosis, and more favorable short-term neurodevelopmental outcome were recorded in patients identified through expanded newborn screening. (PMID 16763906). Propionic acid is an organic acid. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart, kidney and liver abnormalities, seizures, coma, and possibly death. These are some of the characteristic symptoms of untreated Propionic acidemia. Many affected children with organic acidemias experience intellectual disability or delayed development. When propionic acid is infused directly into rodents' brains, it produces reversible behaviour (e.g., hyperactivity, dystonia, social impairment, perseveration) and brain changes (e.g., innate neuroinflammation, glutathione depletion).