Luminal carbohydrate substrates leading to short-chain fatty acid production

Luminal carbohydrate substrates refer to a diverse group of non-digestible dietary fibers and prebiotics, such as inulin, resistant starch, and fructo-oligosaccharides, that escape enzymatic digestion in the small intestine and reach the colon (Gibson et al., 2017). In the large intestine, these substrates are fermented by the commensal microbiota, a process that generates short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate (Koh et al., 2016). These SCFAs serve as the primary energy source for colonocytes and function as critical signaling molecules that regulate gut barrier integrity, immune homeostasis, and systemic metabolism (Blaak et al., 2020). While not a single molecular target like a receptor, these substrates are therapeutic focal points for modulating the gut-brain and gut-immune axes to treat conditions such as inflammatory bowel disease and metabolic syndrome (Sun et al., 2017). Their physiological effects are largely mediated through the activation of G protein-coupled receptors, specifically FFAR2 and FFAR3, and the inhibition of histone deacetylases (Tan et al., 2014). Consequently, the availability and fermentation of these carbohydrates are essential for maintaining a healthy symbiotic relationship between the host and the gut microbiome.

Other names

Dietary fiberPrebioticsFermentable carbohydratesNon-digestible carbohydratesMicrobiota-accessible carbohydrates (MACs)

Microbial fermentation of non-digestible carbohydrates in the colon produces short-chain fatty acids (SCFAs) like acetate, propionate, and butyrate, which then activate G protein-coupled receptors (FFAR2, FFAR3) and inhibit histone deacetylases (Koh et al., 2016; Tan et al., 2014).