epithelial cells. NF-kB regulates many cellular genes involved in early inflammatory responses (14) (15). The activity of NF-kB is frequently deregulated in colon cancer and in inflammatory bowel diseases (IBDs). Clinical studies show beneficial effects of butyrate administration, directly or via dietary fibre, on inflammation and symptoms in patients with ulcerative colitis (UC, form of IBD). Di Sabatino et al. (2007) demonstrated that the oral butycoat is effective in the treatment of mild to moderate Crohn’s disease. A daily dose of oral butyrate resulted in reduction of the clinical signs and inflammatory parameters in the large intestine.
Intestinal barrier function and antimicrobial activity
Extensive use of antibiotics leads to the emergence of antimicrobial resistance, which is not only an issue in livestock, but also in pet animals. Companion animals are in close contact with humans which increase the risk on zoonotic transmission, moreover, difficult to treat infections, use of antimicrobials which are also important in human medicine and limited control on antibiotic treatments increase concerns for public health. Groups of opportunistic pathogens in pet animals include staphylococci, enterococci, Escherichia coli and Salmonella (16).
Antimicrobial peptides (like defensins and cathelicidins) are essential effector molecules of the innate immune system and are of great importance in bacterial host defence. These peptides, also mentioned host defence peptides (HDP’s), possess broad-spectrum antimicrobial activities against bacteria, protozoa, enveloped viruses and fungi. HDP’s can bind to different types of microbial membranes, cause membrane disruption which results in microbial death (17). This first line of defence and their natural broad-spectrum against microbes, makes the up regulation of HDP’s an interesting approach as alternative or adjunct therapy to antibiotic treatment.
A recent study of Sunkara et al (2011) revealed a novel role for butyrate in the host defence system. Results from this study in chickens revealed that butyrate increases the antibacterial activity of host immune cells by up-regulation of an array of HDP’s in vitro and in vivo. This immune defence was coupled with a minimum impact on immune cell activation and inflammation. More importantly, oral supplementation of butyrate resulted in a significant reduction of Salmonella enteritidis after infection.
Same results of butyrate were seen in other studies in mammels. After antibiotic treatment of Shigella-infected patients, adjunct therapy of sodium butyrate significantly increased the expression of a specific HDP (cathelicidin LL-37) in the rectal epithelium. Accompanied by early improvement of rectal inflammation and reduction of proinflammatory cytokines in the stool compared to the control group (18). Oral butyrate treatment in Shigella infected rabbits resulted in reduced clinical illness, less severity of inflammation in the colon, significant up-regulation of antimicrobials (HDP’s) in the gut and early reduction of Shigella count in the faeces (19).
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. At low doses butyrate down regulates expression of invasion genes in Salmonella, thereby reducing the ability of the bacteria to attach to host cells of the intestinal epithelium, becoming invasive and virulent (20) (21). Other studies confirm the efficacy butyrate on inhibition of pathogen colonization of E. coli (22) and in particular Salmonella (23) (24) (25) .
Finally as major precursor for de novo lipids synthesis used for the cell membrane, butyrate contributes the maintenance of barrier and transporter functions of the gut (10). Especially for butyrate there are indications that it increases the defence barrier of the colon mucosa by stimulation of the formation of mucin glycoproteins. These mucin glycoproteins are essential in the mucus layer which protects the intestinal epithelium (26) (27). Moreover Ma et al. (2012) observed an important role of butyrate in intestinal wound healing through its positive effect on the tight junctions and gut integrity.
Butyric acid is available as the Na, K, Mg or Ca salt (6). Uncoated butyrate is directly available and will immediately be absorbed in the first part of the digestive tract before reaching the large intestine. In order to exert the influence in the large intestine, dietary butyrate should slowly be released over the gastro intestinal tract (28).
The aim of a coating or encapsulation is to have a targeted release in the whole digestive tract. The protective lipid matrix used for microencapsulation of organic acids allows slow-release of active ingredients over the digestive tract, preventing the immediate disappearance of the ingredient (29).
In swines, as well as in chickens, it is shown that coated butyrate is superior to uncoated butyric acid in reducing intestinal Salmonella colonization (24) (25). Thereby environmental contamination and transmission of Salmonella to other uninfected animals was reduced in the coated butyrate group. The researchers suggest that uncoated butyrate is taken up by the cells in the upper digestive tract, where as coated butyric acid will influence the colonization of Salmonella bacteria at the site of the colonization, i.e., in the gut (24) (23).
The type of coating influences the release of butyrate over the digestive tract. Proper coating should not be decomposed in the stomach but gradually released in the presence of fat degrading enzymes. By the use of a dissolution test the release rate of sodium butyrate is tested and analyzed. This is done by simulating the same conditions of the stomach and intestinal tract. By testing Excential Butycoat, all butyrate is passing the stomach and is gradually released in the intestinal fluid (39).
In addition to targeted release of SCFA over the digestive tract, coating reduces the typical unpleasant smell of butyrate. Although preferred by some animal species, most pet owners do not prefer the smell of butyrate in pet food. Wageningen University tested the effect of extrusion on odor properties of Excential Butycoat (micro-encapsulated sodium butyrate 30%) in a commercial dog food formulation. During the extrusion process and after packaging of the kibbles, there was no clear difference observed in smell between the control diets and diets with the coated butyrate (30).
Butyrate is essential as an energy source for epithelial cells and vital intestinal function. Diverse beneficial effects of butyrate on animal health can be achieved by the use of dietary fibres and by direct addition of butyrate to the diet. Use of proper micro-encapsulated butyrate, like Excential Butycoat, results in targeted release of the SCFA over the digestive tract, moreover, a reduction of the typical smell of butyrate during production and in the feeding of butyrate containing diets to pet animals.
References on request