Importance of butyrate for gut integrity
Butyrate plays an important role in the development of the intestinal epithelium. It can be utilized by the intestinal epithelial cells as an energy source and stimulates their differentiation and proliferation. The intestinal mucosa is one of the most rapidly replicating tissues in the body and therefore a sufficient energy supply is essential for villi development, gut morphology and absorptive function. Whereas most other cell types utilize glucose as their primary energy source, colonocytes have a great capacity to metabolize butyrate for the production of adenosine triphosphate (ATP) and thus energy. Moreover, butyrate shows to improve the physical intestinal barrier function. The function of the epithelial layer as defense barrier is of great importance, as this single layer of cells needs to protect the inner body of the animal from constant challenges by microbes, toxins, pathogens and other foreign substances. Butyrate has a positive effect on the tight junctions, increasing the connection between cells and improving the barrier strength. As precursor for de novo synthesis of lipids used for cell membranes, butyrate contributes to the maintenance of barrier and transporter functions of the gut. Additionally, there are indications that butyrate stimulates the formation of mucin glycoproteins. These mucin glycoproteins are essential in the mucus layer which protects the intestinal epithelium and forms an additional part of the defense barrier of the colon mucosa.
For newborn animals, quantities of intestinal produced butyrate can be small, although it is an important factor in the development of the growing gastrointestinal tract. Supplemental butyrate in young animals results in beneficial effects on gut development and intestinal function, optimizing both gut and general health.
As organic acid, butyrate also exhibits antimicrobial potency. Undissociated acids, in their uncharged lipophilic form, can cross the (bacterial) cell membrane. Intracellularly they will dissociate, resulting in an increased proton concentration and reduction of pH. Protons will be transported outside the cell on the expense of cellular energy. The accumulation of organic acid anions in the cytoplasm results in metabolic perturbation and compromised function. Bacteria differ in their sensitivity towards organic acids and the effects of different organic acids may vary with environmental pH.
Another mechanistic explanation on the antimicrobial efficacy of butyrate is discussed by the research group of Van Immerseel (2006). An early step in the pathogenesis of bacteria, like Salmonella, is the interaction between the bacteria and host cells. Already with low levels of butyrate, it was observed that the expression of invasion genes in Salmonella bacteria was down regulated. Hereby, the ability to attach to host cells of the intestinal epithelium is reduced, and it prevents Salmonella of becoming invasive and virulent. Other studies confirm the efficacy of butyrate in preventing the colonization of other pathogens such as E. coli.
Unlike other organic acids which have mainly antibacterial properties, butyric acid also acts as energy source for epithelial cells and as an important signaling molecule. The positive effects of butyrate on intestinal health have already been described in many reports. In broiler chickens, supplementation of butyrate in feed can beneficially influence intestinal villi structure and improve growth rate and feed conversion. It is also observed that the birds’ immune response is improved, and pro-inflammatory pathways are downregulated.