Digestion and absorption of nutrients are the major roles for the intestines, as well as the prevention against the entry of antigens and microorganisms into the blood. However, the impairment of the intestinal barrier function and its increased permeability (‘leaky gut‘) can lead to poor performance and disease.
The intestinal barrier is mainly constituted by a single layer of epithelial cells, including enterocytes, goblet cells, paneth cells and enteroendocrine cells, and also immune cells. The cohesion between these cells and thus, the regulation of the intestinal permeability is ensured by a dynamic protein complex called ‘tight junctions’. The interaction between its physical, physiological and immunological components enables a balanced permeability, providing an effective defence to macromolecules, bacterial products, and food antigens, but allowing a small fraction of molecules to cross the tight junctions and facilitating the co-existence with the intestinal microbiota without causing any harm.
Several studies showed a positive effect of isoquinoline alkaloids supplementation on the intestinal barrier function of pigs. Photo: Hans Banus
Stress and inflammation breakdown the intestinal barrier
Several factors including stress and inflammation have been identified to breakdown the intestinal barrier, thus increasing intestinal permeability and allowing the entry of macromolecules and endotoxins, which causes the activation of the immune system. Furthermore, the subsequent immune response suppresses appetite and redirects energy and nutrients towards the immune response and away from production purposes. An activated immune system requires large amounts of energy and nutrients that could otherwise be used for growth. It is estimated that the mucosal immune response can cost up to 30% in detriment of growth. Moreover, stress associated with weaning and high ambient temperatures, for instance, are known to activate inflammatory cells to produce pro-inflammatory cytokines, which have deleterious effects on the intestinal morphology, compromising the intestinal barrier integrity. Therefore, there is an obvious need to develop strategies to minimise productivity losses when physiological states or environmental conditions activate the immune system.
Pro-inflammatory cytokines have deleterious effects on the intestinal morphology, compromising the intestinal barrier integrity, as seen here. Photo: Phytobiotics Futterzusatzstoffe GmbH 2017
A healthy intestinal barrier function
Effective management and feeding strategies that limit intestinal inflammation and promote gut health while reducing the use of antibiotics are essential to improve growth performance and ensure the profitability of the animal production system. Herbal extracts from Macleaya cordata (plume poppy) have been extensively investigated as an effective nutritional strategy to improve growth performance while promoting intestinal health. The isoquinoline alkaloids (IQ), particularly benzo(c) phenanthridine and protopine alkaloids present in plume poppy have demonstrated pronounced anti-inflammatory effects. Several research studies show that acute phase proteins and other biomarkers of inflammation are significantly reduced in food animals fed IQ, while production parameters are improved. In addition, a reduced damage to the intestinal mucosa was observed when IQ were included in the diet of broilers and pigs challenged with enteric pathogens, such as Clostridium perfringens and Salmonella enterica. Moreover, supplementing pigs with IQ has shown to down-regulate stress response, thus reduce the negative effect of stress on the intestinal mucosa. Therefore, as inflammation and stress are very well-known triggers of intestinal barrier dysfunction, the effect of IQ supplementation on the intestinal barrier was further investigated.
Figure 1 – Effect of IQ supplementation on the electrical resistance (TER) of the intestinal barrier in piglets.
Effect of IQ supplementation
The first study was conducted in North Carolina State University (USA) by Robbins et al. (2013). In this study, trans-epithelial resistance (TER) was measured in ileum samples collected from nursery pigs as an indicator of the integrity of the intestinal mucosa. The results showed that IQ supplementation (Sangrovit®, Phytobiotics, hereafter called IQ supplementation) increased the electrical resistance of the intestinal mucosa by 47%, which is indicative of an enhanced integrity and a higher resistance of the mucosa to the entry of potential macromolecules and pathogens (Figure 1). Consequently, a smaller number of bacteria, toxins and other antigens would have access to sub-epithelial tissues to activate the immune system. More recently, a research study conducted by Liu et al. (2016) confirmed the positive effect of IQ supplementation on the intestinal barrier function. In this study, the expression of a group of proteins involved in maintaining the selective permeability of the intestinal mucosa (tight junction protein complex) was assessed in growing pigs. The results showed that the expression of tight junction proteins was significantly improved in growing pigs fed IQ, reflecting a stronger and more resistant intestinal barrier (Figure 2). In addition, these pigs had 4.5-4.6% higher fed intake and weight gain and a substantially lower diarrhoea score, confirming that IQ supplementation supports the maintenance of intestinal integrity.
Figure 2 – Effect of IQ supplementation on the expression of tight junction proteins in piglets.
IQ supplementation could be used as a nutritional strategy to improve gut health and prevent the occurrence of a ‘leaky gut’, thus maximising the use of nutrients for performance in a more efficient manner.
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