01.03.2019

Ghent University Research: Resin Acids Protect Gut Epithelium

Hannele Kettunen, R & D Manager

“No foot, no horse” is an old saying among horsemen. The proverb reflects both the susceptibility of horse feet to injuries and the importance of healthy feet for horses. For poultry producers, the saying could go as “No gut, no poultry”. Efficient nutrient uptake and feed conversion are crucial for the economics of modern poultry production. Industry professionals know how easily gut functions are disturbed. 

Key contributor to the proper functioning of gut epithelium is collagen. This highly abundant protein gives strength to bones, tendons and all other connective tissues throughout the body. Intestinal epithelial cells are literally attached to the collagen-rich basal membrane (shown in red in Figure 1). The extracellular matrix under the intestinal epithelial cells is also enforced with collagen fibres.

Figure 1: Villus of broiler jejunum: intestinal epithelial cells (brown), collagen (red)

The delicate balance of intestinal mucosa can be challenged by pathogenic bacteria, fungi, viruses, mycotoxins, heat stress, low-quality diet, or other stressors. Prolonged stress to gut epithelium leads to inflammatory processes, including increased production of specific enzymes which degrade collagen fibres: matrix metalloproteinases (MMPs). Collagen degradation by MMPs damages gut epithelium and reduces surface area for nutrient uptake. Gut barrier function is also weakened, resulting in the entrance of bacteria and their cell wall structures: the proinflammatory, fever-inducing lipopolysaccharide, LPS.

RESIN ACIDS REDUCE ENZYMATIC BREAKDOWN OF COLLAGEN

The newly published scientific article from the research group of professors Filip van Immerseel and Richard Ducatelle (Faculty of Veterinary Medicine of the University of Ghent, Belgium) demonstrated that inflammation-associated collagenolytic activity of MMPs of broiler gut is significantly suppressed by in-feed resin acids (Aguirre et al., 2019). In essence, the natural resin acid composition of Nordic coniferous trees inhibits collagen breakdown in the absorptive epithelium of broiler chicken and thus supports mucosal integrity against a variety of stressors.

The scientists had two groups of broiler chickens: a control group fed with a commercial-type diet without resin acids, and the resin acid group with a dietary amendment of resin acids at 200 mg/kg. When the chickens were 22 days old, samples of their small intestinal tissue was analysed for enzymatic activity for collagen degradation using a commercial EnzChek® Assay Kit. Significant decrease in collagen breakdown was detected in ileum and jejunum, but not in the duodenum of the birds. However, a histological analysis revealed that the density in inflammation-associated T-lymphocytes was significantly decreased in the duodenal tissue of resin acid -fed birds. Thus, the anti-inflammatory effects of resin acids took place in all the three main compartments of the small intestine.

The most profound effect of resin acids was observed in the ileum, in which the degradation of collagen types I and IV were significantly reduced. Both collagen subtypes are needed for the mucosal integrity: collagen type I is found in extracellular matrix, whereas type IV collagen is an integral component of basal membrane. Furthermore, gelatinase activity was also reduced by in-feed resin acids. The term “gelatin” refers to individual subunits of the large, triple helical collagen molecule. 

The finding was verified by another methodology called gelatin zymography. Ileal tissue lysates were placed into a gelatin-containing polyacrylamide gel, which was subjected to electric current in order to physically separate different enzymes in the samples. The enzymes were next allowed to digest gelatin from the gel, followed by a visualization of those areas in which the gelatin had been digested. Zymography revealed that three gelatinolytic enzyme types were active in the ileal tissue of control birds but only one in the resin acids group. 

According to the authors: “The main enzyme responsible for the reduced collagenolytic activity in the resin acids group had a molecular weight corresponding to both the latent and active forms of MMP7. (…) In the healthy intestine, various MMPs are expressed, but the production of MMP7 is mainly linked to injured epithelium and seems not to be involved in regular epithelial renewal”. Thus, resin acids inhibited the very type of MMPs that is induced by intestinal inflammation caused by any stressor. This is the first time such a gut-protective effect has been demonstrated for a natural feed supplement.

The same research also investigated possible resin acid -induced changes in ileal and cecal microbiota, but only minor effects on the microbiota composition and its metabolic functions were detected. It appears that the primary effect of in-feed resin acids on broiler chickens is the direct protective action on the mucosa.

As suggested by the authors, future research has been directed towards revealing the newly-discovered phenomena in further detail.

The natural resin acid composition tested in the above-described experiments originated from Nordic coniferous trees. The same resin acid composition is the active compound of Progres® of Suomen Rehu, the only rosin-based feed material in the international markets. Progres® has given consistent performance benefits to broiler chickens in institutional experiments, especially in trials, which have included an intentional challenge factor, like coccidiosis, necrotic enteritis, or heat stress challenge. The protection of gut epithelial structure and function likely explains the observed performance benefits by Progres®.

Do not hesitate to contact us for further information on the resin acids in farm animal nutrition. Please follow the news on our LikedIn page, and visit our team at VIV Asia 2019 (Bangkok, Thailand, March 13-15), IHSIG 2019 (Rome, Italy April 3-5) and ESPN 2019 (Gdansk, Poland, June 10-13);

REFERENCE

Aguirre M., Vuorenmaa J., Valkonen E., Kettunen H., Callens C., Haesebrouck F., Ducatelle R., Van Immerseel F., Goossens E. (2019) In‑feed resin acids reduce matrix metalloproteinase activity in the ileal mucosa of healthy broilers without inducing major effects on the gut microbiota. In: Veterinary Research 50:15.

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