The intestine is the first barrier against pathogens. Its correct functionality will be decisive to prevent the infection of pathogenic bacteria, keeping the animals healthy and robust (more information in: "Elements involved in gut health").
Certain probiotic microorganisms have been described to have the ability to interact with the intestinal epithelium, improve the barrier function by increasing the expression of proteins that form the intraepithelial junctions (Putaala et al., 2008), enhance mucin production (McCracken and Lorenz, 2001) and increase antimicrobial peptides such as lysozymes or defensins (Schlee et al., 2008). On the other hand, it is also interesting to note the role of the amino acids threonine (a major component of mucin), glutamine (fuel for intestinal cells, it promotes the repair of intestinal morphology) and arginine (involved in important metabolic cycles). All of them play an essential role in the maintenance of intestinal integrity and have been attributed the ability to improve intestinal morphology and exercise protection against pathogens (Pérez and Nofrarias, 2008; Ewaschuk et al., 2011; Liu et al., 2008).
The immune response will sometimes have to be stimulated (for example in weaning or infections) and in other cases, it will have to be restricted (for example against certain allergenic agents). This modulation is very important to obtain a good gut health, prevent the animals from getting sick, and it is also directly related to other vital functions such as the promotion of a favorable microbiota, absorption of water or nutrients, energy metabolism and eventually productive efficiency.
The influence of lipids on the immune response has been widely documented, since fatty acids are structural components of cell membranes, signaling molecules and precursors of the synthesis of eicosanoids (inflammation promoters). Therefore, the inclusion of ingredients rich in omega 3 polyunsaturated fatty acids can directly affect immunoregulation.
The immune response can also be influenced by protein sources of high biological value, such as spray-dried porcine plasma, egg yolk or bovine colostrum. Much of its effect is due to the passive protection they transmit to animals, due to their high content of active immunoglobulins, but in turn, they are also able to modulate the intestinal immune system thanks to its richness in other active metabolites. An example of its modulation capacity was reported by King et al., (2007), who observed an increase in T lymphocytes (CD4 + and CD8 +) of the jejunal lamina propria in animals that consumed bovine colostrum.
On the other hand, among the bioactive peptides with immunomodulatory capabilities, the glycomacropeptide stands out, with demonstrated ability to modulate the inflammatory response by reducing the expression of proinflammatory cytokines and chemokines in the porcine intestinal epithelium (Hermes et al., 2011). Another example would be lactoferrin, which has been attributed anti-inflammatory and immunostimulant potential in piglets (Wang et al., 2006); or epidermal growth factor, which can stimulate the development of the intestinal mucosa and increase the levels of adherent IgA (Lee et al. al., 2006).
The ability of probiotics to modulate the immune response has also been widely described. They act on the animal's immune system by stimulating the pattern recognition receptors (PRRs), and in particular, it is believed that its main effect is due to the interaction with the Toll-Like Receptors (TLRs). It is interesting to note that depending on the specific strain used and its concentration they can either provide inflammatory responses, enhancing the immune response and activating the expression of antimicrobial factors (Wang et al., 2009); or on the contrary, exert an anti-inflammatory effect and tolerance to luminal stimuli (Siepert et al., 2014). On the other hand, the role of inferring on the immune response has also been attributed to certain specific prebiotics, such as lactulose (Krueger et al., 2002) or β-glucans (Hahn et al., 2006). However, it is considered that a large part of the effect that both prebiotics and exogenous enzymes can exert on the immune response is indirect, through the modulation of the intestinal microbiota.
Another strategy widely used in the sector is the inclusion of zinc oxide (ZnO) at supra-nutritional or therapeutic levels (> 2500 ppm). Although its mechanism of action is unknown, some of its effects are attributed to its participation in numerous regulatory enzymes of metabolism and gene expression. The problems of soil contamination with heavy metals derived from its use limit the inclusion of conventional ZnO. However, the market currently has much more efficient commercial products, such as microencapsulated ZnO, with analogous effects at much lower concentrations (100 ppm) (Kim et al., 2010). It is expected that these new compounds will gain much popularity in the future, as there is increasing legislative pressure to stop using conventional ZnO.
Finally, we’ll finish with an observation. It is important to remember that, although you can modulate the immune response through the use of additives and functional ingredients, its effectiveness can vary depending on the situation. Increasing the immune response can prevent clinical or subclinical diseases, but at the same time, it has a cost in terms of energy for the host. On the contrary, the suppression of the immune response can help us optimize the use of energy for growth, but it can be bad in situations where animals are challenged. In general, it is expected that the response to these additives and ingredients we’ll be greater when the pigs are stressed, have a weakened immune system or are housed in unfavorable sanitary conditions.