Short-chain fatty acids (SCFAs) are organic acids generated by gut microbial fermentation of prebiotics, specifically undigested dietary carbohydrates, resistant starches, and dietary fibers. SCFAs are products of the metabolic effects of the microbiota and their interactions with food sources. SCFA levels are associated with obesity and diabetes: The gut microbiota appears to influence obesity and the development of type 1 and type 2 diabetes mellitus (T1D and T2D). Acetate, propionate, and butyrate—the most abundant SCFAs in our system—are produced by the gut microbiota in a roughly 3:1:1 ratio. Most are metabolized directly in colonocytes; the remainder is absorbed into the hepatic portal circulation, which provides energy to the liver, muscle, kidney, brain and heart. Absorbed into gut epithelia, acetate enters the tricarboxylic acid (TCA) cycle (also known as the citric acid cycle or the Krebs cycle) after being converted to acetyl CoA, and it produces ATP, cholesterol, and fatty acids. Propionate is the primary gluconeogenic substance in ruminants. Propionate is a (relatively small) substrate for gluconeogenesis in nonruminants, including humans, and is formed by the -oxidation of odd-chain and branched-chain fatty acids.