Influence of nutrition on immune system

“Modulation of immune function in food producing animals designed to optimize gut health, general well-being and production performance- with special emphasis on yeast cell wall components”

Introduction

One of the most important changes in livestock production over the past 20 – 30 years has been the shift from disease treatment towards prevention. On a world-wide scale this phenomenon has been accelerated by three major events. Firstly, the realization that losses due to mortality and morbidity have a major impact on the profitability of the livestock operation and that they can be reduced significantly through improved management and nutrition. Secondly, the evidence that has become available on the critical implication of the immune system in the major physiological events in the animals life, especially at high levels of production. Thirdly, and more recently, promoted by consumer demands, the search for alternatives to the use of antibiotics.

Key to these three components is the role of the immune system and the realization that nutrition has a major influence on this system. (Scrimshaw 1991). This is especially true for the gut associated immune system. Not only does this system control the largest interface between the environment and internal tissues (thus representing the largest part of the mammalian immune system) but also because the gut associated immune system confers a first defense against infection and is known to have a significant semi-independent nutrient requirement (Klasing, 1998).

Understanding the mechanisms by which nutrition influences immunity – and especially the GIT-associated immune system – is thus critical in further increasing animal productivity.  Simultaneously, it will enhance sustainable and responsible animal production based on the animal’s well-being as a primary consideration. A number of nutritional interventions have been offered to enhance the gut associated immune status. Most of these are based on the use of natural additives especially yeast derived products (Ferket et al., 2002; Petigrew, 2000). Understanding of the interaction between the immune system and these yeast components will contribute significantly to a better understanding of the functioning of the immune system and ways to modulate it through nutrition.

 

Basic aspects of immune system – with emphasis on the G.I.T.

In healthy and productive animals the immune system provides a layered defense of increasing specificity against pathogens. Physical barriers such as skin and membranes constitute the first barrier and generally prevent pathogens from entering the organism. If a pathogen breaches these barriers, which logically most easily occurs at the gut and respiratory level, the innate immune system provides an immediate, non-specific response. However, if pathogens successfully evade this second tier protection, vertebrates possess a third layer of protection, the adaptive immune system.  The latter is activated by the innate response. During an infection the healthy immune system develops a long lasting immunological memory of the invading organism. This allows for recognition at a following invasion and results in a faster and stronger attack each time this pathogen is encountered (Mayer, 2006) thus reducing the productive consequences of a future infection.

In all livestock species the entire range of immune barriers are present and these systems act to protect all entry points from pathological attacks. This is especially true for the gastro-intestinal tract (GIT) (the dominant entry point for potential harmful organisms) where a continuously regenerating mucus layer serves as a protection against micro-organism or toxins. Embedded in this mucus layer is a portion of the immune system (the mucosal immune system) which protects the mucus membrane against infection, prevents the uptake of antigens, microorganisms, and other foreign materials, and moderates the organism’s immune response to this material. The mucosal immune system is highly specialized and is composed of an innate and adaptive component. These systems protect the surface and thus the body interior against potential pathological invasions. In healthy animals, this local immune system contributes in excess of 70 % of all immunocytes. These cells are accumulated in, or in transit between, various mucosa-associated lymphoid tissues (GALT – Gut associated Lymphoid Tissue), which forms the largest lymphoid organ system (Burkey et al., 2009).

The GALT is highly selective in its functions and like other mucosal lymph systems has three main functions: (i) to protect the mucous membranes against colonization and invasion by potentially dangerous microbes, (ii) to prevent uptake of undegraded antigens including foreign proteins derived from ingested food and commensal microorganisms, and (iii) to prevent or reduce the development of potentially harmful immune responses to these antigens if they do reach the body interior. Consequently, while confronted with a maximum amount of digesta the healthy GALT must economically select appropriate effector mechanisms and regulate their intensity to avoid tissue damage and immunological exhaustion (Holmgren and Czerkinsky, 2005).

The GALT functions independently of the systemic immune system and includes the Peyer’s patches, the mesenteric lymph nodes and solitary follicles which serve as the principal mucosal inductive sites for the initiation of immune responses.  The GALT is populated by T cells, B cells, and accessory cell subpopulations. The B lymphocytes produce large quantities of secretory immunoglobulin A (IgA) which is the only type of antibodies that is efficiently secreted through the epithelial cells into the lumen of the GIT (Burkey et al., 2009). The determining features of the specific cells and associated complex cascading mechanisms involved in the GIT immune response have been described in detail (Burkey et al., 2009; Mowat, 2003; Holmgren and Czerkinsky, 2005).  A high degree of selectivity and tied regulation of the mucosal immune system is essential if effective immune function and tolerance against specific antigens is to be maintained. Especially since this has to be accomplished in the face of the enormous amount and diversity of potential antigens present in the feed and micro-flora (or parts thereof).  Clearly, the supply of nutrients or additives to support or regulate the intestinal immune system must take these specificities into account – especially since these are not constant throughout the animal’s life.

The gut associated immune system is extremely dynamic and evolves with the various physiological stages of the animal. At birth, the neonate’s mucosal immune system is relatively undeveloped. A rapid development of the gut associated lymphoid tissue (GALT) occurs concomitantly with the development of digestive structures and functions. Nutrient supply and colonization of intestinal flora accelerates development resulting in a functional immune system shortly after birth or hatching. In the young as well as mature animals – in the absence of a significant challenge – the GALT assures the basis for continuous GIT health and is able to sort between non pathogenic and pathogenic antigens and swart feed-borne threads to the system.  Despite this homeostatic orientation, certain physiological events and productive pressures will lead to a decrease in GIT associated immune response and increased exposure to pathogens.  Many of these events are associated with natural changes in hormone balances which have a direct effect on the over all immune response and consequently on the GALT (Davis, 1998). The GIT associated immune system activity and requirements varies thus with a number of conditions of the host animal. These conditions are primarily: (i) stress associated with high levels of production; (ii) weaning or hatching (iii) parturition, (iv) reduced feed intake and (v) sub-clinical disease status. Under these conditions or crucial stages in the animals life it is essential to assure a nutrient supply that is in line with maximizing GALT function and stimulating overall immunity if productivity and well being of animals is to be maximized.  Specific nutrients and additives can play a major role in this endeavor.

 

Gut immune stimulation through dietary components.

From birth on animals receive diets and nutrients in greatly varying amounts and composition. The animal and the immune system have to develop (and maintain) strategies to deal with the variations in amount and composition. To complicate matters, nutrient supply for maximum performance or immunity – especially the GIT immunity – is not necessarily the same and the hierarchy among the two systems changes with level of production or exposure to pathogens. As a matter of fact, the objectives of the GIT in terms of production or immunity are often conflicting. A highly activated immune system reduces production potential due to its requirements for nutrients, primarily energy, thus reducing available energy and nutrients for productive functions. Infections – regardless of their severity – will exercise a tax on the nutritional status and reduce nutrients available for productive functions.

The way in which the immune system interacts with the nutrient requirements and utilization are now well recognized (Klasing, 1998; Scrimshaw 1991). A large body of research has been generated over the past decennia. Although specific requirements for the immune system have not been defined, interactions between the immune system and the nutritional status or requirements are now well accepted.

These interactions can be summarized in three principal mechanisms:

  1. The definite requirements of the immune system for nutrients to assure adequate development and maintenance.
  2. The changes in nutrient requirements (and metabolism) of the immune response as affected through changes in animal behavior or through effects on intake, utilization and partitioning of nutrients.
  3. The effect of the pathology associated with the immune response on nutrient requirements and utilization.

Each of these mechanisms is closely associated with a number of hormonal changes induced or generated by the stress preceding or during infection (Davis, 1998).  The direct effect of these changes is almost invariably a reduction in feed intake. While this may be considered unfortunate in terms of meeting overall nutrient demand, the underlying response is defensive.  A reduction in intake will assist in preserving homeostasis by decreasing endogenous losses, notably enzyme secretions, increasing concentrations of IgA and reducing nutrient supply to harmful bacteria. Infections at the GIT level induce the immune system to produce pro-inflamatory cytokins which act on the neural structures (especially the hypothalamus) responsible for regulating appetite and satiety. These cytokines have an over-riding effect on the animal and make it difficult, if not impossible, to stimulate intake. Alternatively, restriction of feed intake as is often used to reduce production stress and metabolic disorders will reduce the systemic immune system responses but does not appear to reduce the weight of selected GIT associated immune organs or IgA production (Fassbinder-Orth and Karasov. 2006).  Applied over longer periods, feed restriction also seems to increase lymphocyte proliferation, interleukin-2 production, and T-cell development and function (Pahlavani, 2000). Increasing nutrient supply to stimulate the immune system and reduce the immune challenge can thus only be achieved through changes in nutrient density of the diet.

 

Incorporating the immune system in feeding strategies

Historically, and from a nutrient supply point of view, the immune system has been considered as part and parcel of the whole animal system with established nutrient requirements for the animal covering the need of the immune system. Over the past decennia, considerable research has focused on the nutrient demand of the immune system and on the effect of specific nutrients to modulate the immune response (Klasing 1998; Leblanc et al., 2006). This implies that the immune system needs to be dealt with on a semi-autonomous basis with specific nutrient requirements, different from the “host animal”.  Despite this general recognition limited attention has been paid to the interaction among nutrients and how “to feed” the immune system – especially in a preventative manner.  While a considerable effort is spent on modeling the nutrient requirements of livestock as a function of variation in requirements, rarely are the specific requirements of the immune system taken into consideration. This despite the dominant effect the immune system can have on nutrient requirements and utilization; especially at the GIT level (Klasing and Barnes, 1988).  The interaction between the maintenance and production requirements of the animals, the need to meet the nutrient demands of the immune system and the nutrient supply is highly dynamic and cannot be met with classical demand-and-supply ration calculations.

The manner in which these nutrients interact with the immune system and the host animal is complex and certainly not entirely clear. Nevertheless, this interaction (and our understanding of it) plays a crucial role not only in priming the immune system in order to prevent or correct health threats but also in the repartitioning and utilization of nutrients for productive functions. A better understanding is thus necessary and this starts with summarizing our current knowledge in this area.

Fig. 1 presents a schematic representation of how interactions between the immune system and nutrient supplies are – or should be – integrated in our feeding systems. From a nutritional point of view our present concept of dealing with the immune system is based on considering the nutrient requirements of the animal and the immune system as identical, thus in an integral fashion (A).

For specific conditions we may incorporate in our diet calculations certain demands of the immune system which implies that we look at the host animals and the immune system in a composite fashion. For instance, special requirements for fatty acids, vitamins or minerals are taken into consideration and are included in the diet.  This often amounts to the supply of an arbitrary supplement of these nutrients above the established requirements. To assure maximal production and well being of the Animal the dynamic nutrient needs of the immune system should be taken into consideration. These are not constant but depend on conditions of production and (environmental or health) challenges (C).  The latter will require additional studies and the determination of nutrient supplies based on dynamic systems.

Article Influence of nutrition on immune system -Figure 1

Specific Nutrient effects

Energy.

As is the case for all metabolic processes, the immune system requires energy in increased amounts during an immune response. It is generally accepted that inflammations are associated with increased glucose utilization obtained through gluconeogenesis. At the same time oxidation of fatty acids as a source of energy is reduced (Beisel, 1977). The net energy impact of this shift in substrate is not known.

The decrease in intake associated with immunological stress can in part be compensated by increasing dietary energy concentrations but the effect of increased energy concentrations on immune response is far from clear. Positive responses have been obtained in poultry by using higher energy intake obtained by increased starch inclusion but not by increasing oil levels (Benson et al., 1993) and relatively small (5 %) incremental increases in energy had no effect on antibody responses and immune organ development in broilers (Praharaj et al., 1999).  Decreasing energy concentration in steers diets below maintenance (from 210 or 60% of maintenance requirements) had little effect on the expression of adhesion molecules by leukocytes, but in some cases expression was increased by negative energy balance (Perkins et al., 2001). Immune response may be more closely related to overall energy status of the animal and only affected by dietary energy concentration in severe energy deficient diets. Body reserves, and the potential to mobilize these reserves, may be of greater importance in affecting immune response or lack thereof. Animals with low body reserves due to prolonged energy deficiency or advanced age are more sensitive to an immune challenge (Ritz and Gardner, 2006).  To prepare for an adequate immune response the maintenance of adequate body protein reserves to assure substrates for gluconeogenesis may be more effective than increased fat reserves; especially around parturition.

Amino acids

Protein and amino acid supply have a greater influence on immune response than energy.  Activation of the immune system – especially in the case of an innate immune response – results in increased skeletal muscled catabolism and, concomitantly, an increase in protein synthesis by the liver and spleen. This repartitioning of amino acids from growth towards immunity reflects a need for amino acids for the production of acute phase proteins involved in the host defense. The composition of skeletal muscle in amino acids being different from that of the acute phase proteins a logical rearrangement in priority of AA requirements takes place (Humphrey et al., 2004). Supplementary effects of individual amino acids on the immune responsiveness must thus be evaluated in light of the amino acid make up of the innate immune system; an ideal protein system for the innate immune system could be in play. However, this ideal amino acid balance is poorly understood and for the moment trials with individual amino acids or limited combinations of amino acids provide the only guidance.

Supplementation with protein and individual amino acids has been carried out with mitigated success.  In poultry arginine supplementation is the most widely investigated but measured responses to this amino acid vary greatly and no clear conclusions can be drawn from a summary of a large number of studies (Humphrey and D’Amato, 2008). The evaluation of the effects of specific amino acids on the immune system will require a large number of dose response trials.  Applying this approach Klasing and Calvert (2000) determined that in a healthy growing chick development, maintenance and use of the immune system accounts for 1-2%, 0.5-2% and 7-10% of lysine intake, respectively. The large increase associated with the immune system is considered to be due to an increase in liver size associated with increased synthesis of acute phase proteins (Barnes et al., 2002).  It is not clear however if an additional lysine supply will enhance the immune system’s activity as it has been shown that pigs with low level chronic immune stimulation have higher lysine requirements than pigs on high level immune stimulation (Williams et al., 1997). A similar observation was made in broilers where a deficiency of Lysine did not impair the ability of the bird to produce circulating IL-1 during immunologic stress (Klasing and Barnes, 1988). This would suggest that the use of lysine for immune stimulation takes priority over use for growth.

The use of other amino acids by the immune system has been identified. Methionine, threonine, cystine and glutamine are some examples.  For all of these amino acids immunological stress has been shown to result in lower requirements. But concomitantly it has been shown that – with the exception of cystine – deficiencies of these amino acids depress the production of immune cells (Humphrey and D’Amato, 2008; Kidd, 2004). Simply increasing the supply of a particular amino acid does not necessary directly translate to increased utilization and improved immune function. Clearly, nutrient partitioning to support and enhance immune function is complex and goes well beyond a simple supply and demand equation in particular for amino acids.

Vitamins and Minerals

Besides energy and amino acids a large array of nutrients has been studied as potential effectors of the immune system.  Among these vitamins, micro-minerals and fatty acids. The effect of vitamins and minerals on the immune system generally follow closely classical nutritional theory i.e. meeting requirements for different functions in a factorial fashion with a hierarchy in which the immune system takes precedent over productive functions. Deficiencies invariably lead to impaired immune cell functioning while excesses of some minerals or vitamins may lead to immune suppression (Kidd, 2004; Spears 2000).

Fatty acids

In classical nutrition fatty acids are primarily considered important sources of energy. However, the work by Beissel (1977) questions the importance of fatty acids as simply energy substrates to support or stimulate the immune response. Over the past decennia an alternative role of individual acids has taken on greater significance. Directly or indirectly, most fatty acids have a major effect on the immune system. This may by at the level of reducing infections and challenges to the immune system or more directly in being an essential part of the immune cell or as effector molecules in the cascading sequence of events that constitutes the immune response.

The role of short chain fatty acids (SCFAs) and medium chain fatty acids (MCFAs) in controlling infections and maintaining GIT health and integrity have been described in detail (i.e. Daskiran et al., 2004; DeCuypere and Dierick, 2003; Morz, 2005). The removal of anti-biotic growth promoters (AGPs) and the need to find alternatives to control bacterial infections in the GIT has contributed much to stimulating the use SCFA as well as MCFAs in monogastric diets. The primary mode of action of the former (SCFAs) is thought to be pH lowering thus reducing microbial pressure in the GIT and their effect on the immune system may thus be considered as largely indirectly.

Not all acids are equally effective in this indirect effect and there is an important difference in minimum inhibitory concentrations (MIC) depending on the type of acid, the targeted microbes and the pH level at the site of action (Nakai and Siebert, 2002). At the same range in pH a number of organic acids are not inhibitory to bacteria while others are. Key to their anti-bacterial action is their characteristic pKa and the degree of dissociation at a particular pH. In general, at low pH values the concentration of undissociated molecules increases (Ricke, 2003). Short chain (<C4) acid molecules need to be in an undissociated state in order to enter the microbial cell. After entering the cell the higher intra-cellular pH results in dissociation and lowering of the internal pH thus disrupting normal metabolism. Especially sensitive to this mechanism are thought to be the gram-negative bacteria such as E. coli and Salmonella spp., and the gram positive Clostridium spp. The mode of action of SCFAs is not limited to a lowering of the pH. Like MCFAs they have a strong anti-microbial effect associated with the anionic fraction of the acid molecule and it is unclear what proportion of the effect is simply pH mediated and what is achieved through direct effects at the level of the bacterial cell metabolism. The effect of the anionic moiety is probably not only achieved through changes in the physio-chemical environment of the microbe but also through their effect on gene expression (of the microbe as well as the host). For instance, of the SCFAs propionate and butyrate appear to regulate the expression of genes that favor invasion of various Salmonella spp. in the enterocyte (van Immerseel et al., 2006). For MCFAs the molecular basis by which these acids reduce salmonella, clostridium and coli spp. remains to be elucidated (DeCuypere and Dierick, 2003 ). Indeed, the full extent and the exact effect of these fatty acids is far from clear. Immuno-modulatory effects by SCFAs has been reported in HT-29 and Caco-2 cells implying that butyrate, acetate and propionate induce an up-regulation of IL-18 expression which itself is implicated in Th1 cell-mediated chronic inflammation (Kalina et al., 2002). For the MCFA a reduction in inter epithelial lymphocytes has been recorded.

Among the SCFAs it is especially butyrate that has attracted attention and a large body of information exists on the application of butyrate or its derivatives in humans and domestic livestock. This in particular in reference to its regulatory role in intestinal tissue growth and immune system development. Among the many functions that have been attributed to butyrate is its role in regulating gene expression in intestinal epithelium and induction of enterocyte growth and differentiation (Pouillart, 1998). But it is difficult to apply general statements in term of butyrate’s effect on the GIT immune system since the role of butyrate in modulating the immune system appears to differ with the (i) level of butyrate present in the GIT, (ii) the type of response evaluated and (iii) the species studied. For instance, Weber and Kerr (2006) provided initial evidence that the effects of high levels of butyrate differ in pigs from what has been observed in other species while at low levels similar responses are observed. This clearly complicates the extrapolation from laboratory conditions to experimental trials or field conditions. Indeed, much of the work on butyrate’s effect has been carried out in vitro and needs in vivo confirmation, especially with fiber enriched diets. Such diets will normally enhance endogenous butyrate (and other SCFA) production thus modulating GIT immune system responses.

No particular direct immune function has been attributed to most dietary long chain fatty acids (LCFAs). However, the opposite is true for LCFAs of the omega-3 and omega-6 series. These two types of fatty acids have received much attention especially what concerns their effect on the immune function. Eicosapentaenoic acid (EPA 20:5 n-3) and docosahexaenoic acid (DHA 22:6n-3) derived from α-linolenic acid are the primary omega-3 fatty acids. Arachidonic acid (AA 20:4n-6) is derived from linoleic acid and is the primary omega-6 fatty acid. DHA and in particular EPA, play an important role in the anti-inflammatory response by decreasing – among other effects – lymphocyte proliferation, cytokine production, NK cytotoxicity, and antibody production. On the other hand eicosanoids made from AA (prostaglandin,PG-2 and leukotriene) are highly inflammatory. An excess of AA-derived cytokines leads to excessive immune responses and inflammation. Optimal immune function requires these acids to be present in a fairly strict ratio that should be lower than 5:1 for omega-6:omega3 (Simoupoulos, 2002). Positive responses to increasing omega-3 fatty acids supply (and thus the omega 3:6 ratio) have been obtained although most of these trials did not use pure fatty acid mixtures but rather fish oil (Korver and Klasing, 1997; Liu et al., 2003).

Additives effects – yeast and yeast cell walls

An important number of additives are available for inclusion in diets of domestic livestock. Many have a direct or indirect effect on the animal’s immunity. However the reported effects of additives on the immune system are often confounded with changes in nutrition, management or direct effects on the pathological agent. Among the additives with immune modulating effects yeast cell wall components stand out because of their diversity in composition, their wide spectrum of effects and their broad application.   Yeast cell wall components used to affect immunity are almost exclusively obtained from Saccharomyces cerevisiae. The composition and active components of the yeast cell wall (YCW) have been described in some detail (Cawley and Ballou, 1972; Lipke and Ovalle, 1998). The largest part of the yeast cell wall carbohydrates are beta-glucans, mainly β-1,3 glucans. Smaller components are β-1,6 glucans, chitin and manno-proteins with β-1,6 glucans assuring a linkage among the various components.  The mannan proteins (approx. 40%) form a layer on the external surface of the yeast. The composition of the YCW can differ significantly depending on the yeast strain, nutrition and growth conditions (Aguilar-Uscanga and François, 2003). Consequently, significant differences can exist between sources of YCW and this has to be taken into consideration when selecting YCW components for specific functions.

The outer layer of the YCW yields the mannose-based complex carbohydrates, the manno-oligosaccharides (MOS) which are considered primarily responsible for the binding of pathogenic micro-organisms. The immune enhancing properties of the yeast cell wall components are considered to be dominantly associated with the β-glucan fractions – most notably the number, location and structure of the β-1,6 glucan side chains.

Yeast or the intact yeast cell wall have limited, or no effect on the immune system – not through the binding of micro-organisms, nor the direct stimulation of the immune response. For a significant effect on either aspect a separation of the two major CW components – in β-glucans and MOS – seems necessary. Methods to isolate this part of the yeast cell wall can thus play a major role in determining the effectiveness of the different fractions and like the source or growth conditions of the yeast this may be a dominant factor causing variability in effectiveness of the components.

A number of beneficial affects have been attributed to the YCW components; all with a direct or indirect effect on immunity and GIT health. However, many of the effects are consequences of the principle properties of the two YCW components:

1) Enhancing immunity – Immune modulation; associated with the β-glucan fraction.

2) Pathogen adsorption – associated with the MOS fraction.

The first effect is directly associated with the β-glucan fraction and its ability to activate leukocytes (Brown and Gordon, 2005). It is thought that this activation leads to enhanced phagocytic, cytotoxic and anti-microbial activities and enhanced production of the pro-inflammatory mediators, cytokines and chemokines most notably IL-8, IL-1β,, IL-6 and TNFα (Czop,1986). These cytokines and other chemicals are known to recruit immune cells to the site of infection and promote healing of damaged tissue following the removal of pathogens (Leibovich, 2005). Clearly, this leads to a reduction of pathogen presence, improved presence of advantageous, commensal bacteria and increased gut integrity.

The second property – pathogen or toxin adsorption – is directly associated with the MOS fraction. MOS will bind to the bacterial lectins (or lectin-like substances) that normally allow the pathogens to bind to the intestinal epithelial cells (Oyofo et al, 1989). It has also been suggested that MOS will enhance secretion by globlet cells of high molecular weight glycoproteins also known as mucins. These mucins are thought to mimic glycoprotein attachment sites of epithelial cell membrane and competitively bind to lectin receptors of pathogenic bacteria especially type-I fimbriae of gram negative pathogens (Baurhoo et al, 2009) These MOS-bacteria or mucin-bacteria complexes are then flushed out with the undigested residues before the pathogenic bacteria can colonize the gut, reproduce or achieve a critical mass through quorum sensing.

The other immune stimulatory advantageous of the YCW such as enhancing commensal microbial population, improved gut integrity, reduction of enterocyte turnover, increased globlet cells, improved nutrient supply to the host and improvements in fermentation (Ferket et al., 2002; Petigrew, 2000;) may be considered a direct effect of the main properties of the β-glucan and MOS fractions. While both fractions will enhance the beneficial microbial populations in the GIT, neither meets the criteria for a pre-biotic i.e. being a selective and stimulating substrate for the beneficial micro-organism (Gibson and Roberfroid, 1995).  The beneficial effects of both β-glucans and MOS should thus be seen as the first step in a cascade of events that lead to overall performance enhancement. Since each has a specific effect in this sequence of events, achieving the full potential a combination of these separated YCW components may be necessary.

In order for YCW components, especially the β-glucan and MOS fractions, to exercise their respective basic functions they should be indigestible or at least resist digestion – especially in the upper digestive tract (small intestine). Furthermore, they should retain their structural characteristics if they are to be active. Experimental data on the digestibility of YCW are limited. It is generally accepted that the level of mannases and glucanases that can break these compounds down is low (Brown and Gordon, 2005) but some digestion appears to be taken place. Digestibility of YCW components has been measured in broiler chicks and rats (Longe et al., 1981).  Rats digested  47% of the -glucans and 42% of the mannans but the value obtained for chicks was 13 % for mannans while values for -glucans were between 3.3 and 11.7%. In veal calves the digestion of YCW has been determined with an average ileal digestibility of 26 % but a fecal digestibility of 92 %  (Gaillard and van Weerden, 1976). These workers also determined that glucans were more resistant to digestion. Similar results were obtained on 4 calves raised to 102 days of age but maintained on a milk replacer diet (Besle et al., 1980). These workers noted an increase in digestion of YCW components with age and also a higher digestion in the lower GIT. Digestion of mannans and glucans in the small intestine did not change significantly with age. It is also interesting to note that that variation in digestibility among animals was large.

These results would indicate that the activity of YCW decreases as digesta progresses along the GIT and that their greatest activity likely is at the beginning of the small intestine. Bacterial fermentation is potentially important as indicated by their disappearance in the large intestine. Alternatively, sub-fractions of the β-glucans and MOS may retain their activity although the immune stimulating activity of low molecular weight β-glucans is considered minor (Brown and Gordon, 2005). The exact fate of the YCW components in the GIT remains to be further elucidated.

Performance responses and effects of YCW components have been observed and reported in most domestic livestock species. The number or extent of the reported beneficial effects is largest in poultry, less in pigs and to a limited degree in ruminants. Clearly the rumen represents a formidable obstacle for YCW to exercise a direct effect. As a matter of fact, little is known about the fate of YCW in the rumen or the interactions between YCW and the vast and divers rumen microbial population. This is – or should be – a subject of interest and study in its own right.

Performance enhancements, primarily due to the immune modulating effects of glucans, have been reported; especially in the presence of an immune challenge (i.e. Li et al 2006).  However the response can be variable and is not always accompanied by a unequivocal and measurable immune response (i.e. Rathgeber et al., 2008) or inversely a performance enhancement associated with a measurable immune response (Hahn et al. 2006). Clearly, if β-glucans are primarily active as immune modulators it is most unlikely that a performance response will be observed in the absence of an immune challenge or a health threat. On the other hand, β-glucans – due to the broad and general character of the immune enhancing response they elicit – may not be able to overcome an excessive challenge. This despite the fact that an improvement in certain aspects of the immune response maybe observed (Huff et al., 2006).  For instance, the observed decrease in  gram negative bacteria maybe obtained through the secretion of IgA or other mucosal antibodies but this may be too small to affect performance.

Reports on positive performance responses to MOS are numerous and more readily available than for β-glucans; especially in birds and piglets (Ferket et al., 2002; Petigrew, 2000). MOS addition to diets has shown to reduce the negative effects of pathological bacteria along with the improvements in gut health and integrity resulting in performance enhancements. While direct immune stimulatory effects have been attributed to MOS the reports available do not allow drawing a clear conclusion and an indirect effect remains the most probable explanation for the observed changes in immunological parameters.

While most workers agree that β-glucans and MOS components can play an important role in improving immune and health status of especially mono gastric animals and that they represent a viable alternative to antibiotic growth promoters the data in the literature provide a rather large variability in performance response. This despite fairly consistently reported improvement in health status – especially at the GIT level. Improvements in product specifications and definitions along with a more precise recommendation for application will most likely allow improvements in predicting production responses (and rational inclusion in diet formulations).

 

Take home message.

Production pressures along with consumer demands for improved animal well-being and removal of AGP have placed immunity and our capacity to modulate the animal’s immune system in the forefront of animal production concerns. The immune system and its response to nutritional interventions remain poorly understood; this is especially the case for the gut associated immune system. The nutritional cost of an immune response is rarely taken into consideration despite the realization that such a response may represent a significant (dietary) cost.  At present, no – or limited – specific provisions are made in our diet calculations to improve the immune response and reduce losses associated with this response. Incorporation of the specific nutrient requirements of the immune system in the overall nutrition of the domestic animal may improve the animal’s health and well being, productive capacity and global cost of production.

Positive responses in immune stimulation and immune status have been obtained by supplying specific nutrients. This is especially the case for the classical nutrients such as amino acids and vitamins or micro-minerals. However, specific fatty acids may provide an easier means to directly or indirectly affect the immune response at the GIT level. In this – as well as other interventions – the role of commensurate microbial population will need to be taken into consideration.  Many of the existing, recognized, nutritional interventions aimed at modulating the immune response interact directly with this microbial population and may be affected through this interaction. The example of specific components of one group of additives – the yeast cell wall components – could be taken as a case in point. Yeast cell wall components can effectively stimulate the GIT immune system through a direct effect (β-glucans) and indirectly through modifying the microbial population. In both cases beneficial responses in production and animal well- being have been obtained.

Author:

Jan van Eys
Nutriad International

 

References.

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