Short-Chain Fatty Acids:

What Are They, and How Do They Connect to the Microbiome?

Short-chain fatty acids (SCFAs) are postbiotics that are produced as byproducts when gut microbiota ferment prebiotic substrate. Typically, this prebiotic substrate consists of partially digestible and non-digestible polysaccharides – these are carbohydrates, which include various types of fiber and starch. In addition, people can also take a prebiotic supplement in order to feed their gut microbiome. As the bacteria in the gut digest and ferment the prebiotic substrate, they create SCFAs as metabolites or end products. The production of SCFAs is more efficient when an individual has a healthier, higher-functioning microbiome. When there is more “good” bacteria in the microbiome, they are able to effectively ferment the fibers and starches that are coming in and produce higher levels of SCFAs.

It is considered a “short-chain” fatty acid when it has less than six carbon atoms in its structure. Fatty acids can also have a long chain of carbon atoms, for example, Omega-3 fatty acids can have upwards of 20 carbon atoms. Omega-3s include compounds like EPA and DHA, which are also greatly beneficial for human health. There are five types of SCFAs, but the three main ones are acetate, propionate, and butyrate. These three make up 95% of SCFAs in the body, and each has its unique roles in generating energy sources, synthesizing lipids, and serving as signaling molecules for various gut-organ connections. Let’s take a closer look at how they affect the microbiome and the rest of the body.

The Roles of Short-Chain Fatty Acids

There are many roles that SCFAs play across different biological systems. To start, SCFAs are an important energy source: propionate assists by producing glucose in the small intestine and the liver, butyrate is the main source of energy for the cells lining the colon, and acetate works to generate energy as well. There are two major signaling mechanisms that are caused by SCFAs. The first is that SCFAs cause inhibition of histone deacetylases (HDACs) – these molecules regulate gene expression, an exceptionally significant part of our health. Scientists agree that there is much research to be done in this area, as gene expression is a process that has many downstream consequences in cell behavior and specific molecule production. Secondly, SCFAs play a role in the activation of G-protein-coupled receptors (GPCRs). GPCRs play key roles in regulating inflammation in the body, balancing metabolism, and reducing the risk of disease. SCFAs also have the ability to affect chemotaxis (movement of cells in a particular direction) and phagocytosis (when cells called phagocytes ingest other cells/particles), induce reactive oxygen species (ROS), alter cell function, and more – in simple terms, SCFAs help the body maintain homeostasis. This is a major goal of the body, as reaching homeostasis allows for efficient internal functioning and the ability to respond to any external conditions that could be detrimental to health.

Another major role that butyrate distinctly plays is in maintaining gut integrity to keep harmful compounds and toxins from entering the bloodstream. Butyrate signals to increase the production of mucin (what makes up the mucosal layer of the gut) to thicken and strengthen the gut barrier, helping to avoid issues like leaky gut syndrome. To read more about the unique role of butyrate and how it serves a signaling molecule across the body, click here.

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