Beyond butyrate: microbial fiber metabolism supporting colonic epithelial homeostasis.

The human gut harbors a diverse community of commensal bacteria that contribute to the digestion of dietary fibers. Previous studies have focused on butyrate, a short-chain fatty acid, as the primary fuel for colonic epithelial cells due to its efficient oxidation and generation of ATP. The high turnover of the colonic epithelium requires additional carbon sources for synthetic processes such as DNA, RNA, proteins, and lipids, which cannot be fulfilled solely by butyrate. Glucose, a universal carbon source for mammalian cells, can be obtained from the blood circulation and may also be generated from microbial metabolism in the gut. Detailed exploration of the production and role of various colonic microbial metabolites in the energy and carbon metabolism of colonocytes challenges the prevailing notion that butyrate is the exclusive preferred fuel. Human gut bacteria produce metabolites that support energy and carbon metabolism of colonic epithelial cells. While butyrate is commonly considered the primary fuel, it alone cannot meet all the carbon requirements for cellular synthetic functions. Glucose, delivered via circulation or microbial metabolism, serves as a universal carbon source for synthetic processes like DNA, RNA, protein, and lipid production. Detailed knowledge of epithelial carbon and energy metabolism is particularly relevant for epithelial regeneration in digestive and metabolic diseases, such as inflammatory bowel disease and type 2 diabetes. Here, we review the production and role of different colonic microbial metabolites in energy and carbon metabolism of colonocytes, also critically evaluating the common perception that butyrate is the preferred fuel. [ABSTRACT FROM AUTHOR]