Nutritional approach to unleash potential under stress conditions

With high density confinement rearing of birds, an additional important role of poultry nutrition is that birds are not only fed for production or reproductive performances but must also be fed to minimize infectious disease and their concomitant stresses. In context of poultry nutrition Industry, problem of immune-suppression has been felt to be prominent due to various factors viz. managemental conditions and intensive production system, high density rearing and infectious diseases. Therefore, it is highly essential to find ways and means for enhancement of immune response by nutritional intervention. Substantial information is available in literature to indicate that administration of certain vitamins, minerals, amino acids and their different combinations to mammals and chicken in excess of their supposed requirements enhances their disease resistance. This increased resistance has been attributed to significant stimulation of humoral and cellular immunity and phagocytosis. Since, the use of antibiotics has been limited, better use of immuno-stimulatory has to be made in the poultry feed supplement.

The immune system of birds benefits greatly from proper poultry nutrition. Not only does the immune system benefit directly from proper poultry nutrition, but indirectly proper poultry nutrition will also prepare the bird for periods of stress, reducing the adverse effects of stress and enhancing recovery from stressful periods. Therefore, in many instances, immune suppression is associated with the stress response in the bird. In animal nutrition the immune system of the bird can be influenced by  in several ways;

1. Anatomical development of lymphoid tissues

2. Mucus production

3. Synthesis of immunologically active substances

4. Cellular proliferation

5. Cellular activation and movement

6. Intracellular killing of pathogens

7. Modulation and regulation of the immune process

Factors related to the genetics of poultry and poultry nutrition, the frequency of their exposure to pathogens, the virulence of the pathogens, and the efficacy of vaccination programs are predominant detriments of the incidence of infectious diseases in poultry flocks. However poultry feed supplement and diet characteristics can modulate a bird's susceptibility to infectious challenges and subtle influences due to the types of ingredients used and assumes critical importance. The bird's susceptibility to an infectious challenge can be subdivided into two components, resistance and resilience.

Resistance refers to the capacity of a variety of anatomical and physiological systems, including the immune system, to exclude pathogens.

Resilience refers to the capacity of the bird to maintain productivity (e.g. growth, feed efficiency, egg production) during an infectious challenge.

The role of poultry nutrition in maximizing resilience is only now being appreciated and this relationship deserves future attention by poultry feed supplement stake holders. There are probably many situations in which diets that optimize resistance to infectious challenges are not optimal for resilience and maximal profitability (Cook, 1996;

Klasing, 1997). However, in many cases it is not known whether the requirement values that maximize productivity in healthy, unchallenged birds are optimal for immuno-competence and disease resistance. An understanding of the mechanisms through which poultry nutrition influences the immune system is necessary to appreciate the many complex interactions between! diet and infectious diseases. Several recent reviews of poultry nutrition and immunity provide an excellent survey of poultry nutrition and immunity, including the impact of toxic components (mycotoxins) that may contaminate the feed (Cook, 1991, 1996; Latshaw, 1991: Dietert et al., 1994).

Mechanisms of Modulation of Resistance

In animal nutrition the mechanisms of modulation of resistance to infectious disease are divided into seven categories. Obviously these categories are overlapping and nonexclusive: single factor may impact the immune system by several of the general mechanisms that are described as well as mechanisms not listed. The first six of these mechanisms relate to the effect of poultry nutrition on the immune system, whereas the last mechanism considers several non-immunological aspects of the diet. The first three categories consider the role of poultry nutrition as substrates for the replication and function of cells. A substrate role is necessary for the initial development of the immune cells. and tissues (Mechanism 1) and during an actual immune response so that responding cells can divide and synthesize and their supply is contraindicated during an infection (Mechanism 3). Though diet may influence processes important to immunity by providing building blocks (substrates) for the construction of cells and molecules, other mechanisms may be even more important for dietary modulation of the immune system in animal nutrition. These include direct regulatory actions on the leukocytes that respond to infectious challenges (Mechanism 4), as well as indirect effects that are mediated by poultry nutrition modulation of the classical endocrine system (Mechanism 5). Furthermore, poultry nutrition may impact the level of pathology resulting from the killing pathways of the immune system (Mechanism 6).

Impact on the Development of the Immune System

The developmental events important for immune competence begin in the embryo and continue during the 1" week following hatching (Gobel, 1996; Ratcliffe et al., 1996). The 1" week of life is a period of rapid expansion of leukocyte populations, seeding of lymphoid organs, and educational events that produce the unique clones of lymphocytes that will mediate immunity later in life. It is not surprising that this is a critical period during which poultry nutrition deficiencies or excesses may impact the immune system. In general, chronically severe deficiencies of micro-poultry nutrition are more debilitating to the development of the immune system than macro-poultry nutrition such as energy and protein. Poultry nutrition deficiencies that are especially damaging to development of the immune system include linoleic acid, vitamin A, iron, selenium, and several of the B vitamins (Cook 1991; Latshaw, 1991: Dietert et al., 1994).

Embryonic development of the chick is known to be very sensitive to vitamin A deficiencies and it has been known for many years that chicks hatched from vitamin A-deficient hens have impaired immunity and decreased resistance to a wide variety of infectious diseases. In poultry nutrition the level of vitamin A that maximizes growth and feed efficiency of broiler chickens (500 mg/kg) is insufficient for optimal development of the immune system. The level needed for maximal growth and efficiency in clean University facilities was used to set the NRC requirement, yet an amount that is 10-to 20-fold higher is necessary to maximize immuno competence of the young broiler chick (Sklan et al., 1994; Friedman and Sklan, 1997). However, excess of vitamin A can also impair immuno-competence, probably by causing secondary deficiencies of other fat soluble vitamins (Veltman et al., 1984; Friedman and Sklan, 1997).

Micronutrient of the hatchling is very dependent upon the poultry nutrition given of the laying bird (Naber and Squires, 1993). The level of stores of most of the vitamins and trace minerals in the hatchling are highly correlated with the level in the breeder's diet. Sufficient stores may completely buffer the young chick against severe deficiencies during the critical early weeks when the immune system and the intestines develop. Thus, the role of on the developmental events of the immune system must consider the diet of the hen as well as the diet of the chick.

Substrate Supply

Defense against an infectious challenge requires a highly integrated response by the immune system. From a poultry nutrition viewpoint, substrates (e.g. amino acids, energy, enzyme co-factors) are needed to support the clonal proliferation of antigen-driven lymphocytes, the recruitment of new monocytes and heterophils from bone marrow, the synthesis of effector molecules (e.g. immunoglobulins, nitric oxide, lysozyme, complement), and communication molecules (e.g. eicosanoids, cytokines). A quantitative summation of the poultry nutrition along with poultry feed supplement  costs of maintaining the immune system and the additional costs of a vigorous immune response against a challenge is not known for any species.

Though the rate of synthesis of specific immunoglobulins increases dramatically during a disease challenge, the rate of synthesis of total immunoglobulins increases only moderately. Hyperimmunization, for example, results in about a 25% increase in serum immunoglobulin (Leslie and Clem, 1970). Based on serum concentrations and half- life estimates, other humoral components contribute an order of magnitude less to daily synthesis than do immunoglobulins. This analysis of the size of the immune system and rates of its processes suffers from the use of cross-species data and lacks attention to specific issuesthat may be concentrated in leukocytes or preferentially utilized by them (e.g.. Arginine and Glutamine). Even with these qualifications in mind, it is apparent that the amount of substrate resources including that of poultry feed supplements needed by the immune system is very low relative to needs for growth or egg production.

For example, the weight of new leukocytes and immunoglobulins normally produced each day (about 800 mg/kg body weight) appears to be less than 1% of the total increase in body weight of a 2-wk-old broiler chick and less than 10% of the amount of breast. Muscle synthesized each day. Even if an infectious challenge increases the rate of leukopoiesis by considerably more than the twofold estimates that have been reported, it is doubtful that the immune system would be a significant consumer of poultry feed supplements. It is often stated that the depression in performance that is associated with an immune response is due to the diversion fom growth or egg production to be used by the immune system. Given the above quantitative analysis, this statement cannot be true. However in animal nutrition , the immune system is not the only system that increases use during an infectious challenge. Many infections are accompanied by an acute phase response, which is characterized by the synthesis of acute phase proteins, fever, accelerated whole-body protein turnover, and high rates of hepatic gluconeogenesis. The acute phase response includes changes in metabolism and poultry nutrition fluxes in all organ systems of the body, especially liver and muscle. Although descriptive information on the acute phase response of chickens has been detailed (Klasing and Johnstone, 1991) the poultry nutrition demands of this response are not well described. Clearly the acute phase response is a process that is both poultry nutrition liberating (skeletal muscle catabolism) and poultry nutrition consuming (acute phase protein synthesis, fever). Given the marked increase in hepatic demand for amino acids to support gluconeogenesis and for acute phase protein synthesis, it is likely that the amino acid costs of an acute phase response are considerably greater than the relatively minute needs of leukocytes that respond to an infectious challenge (i.e. the immune response) For several poultry nutrition  elements (e.g. zinc, iron, copper, lysine), it is known that the amount liberated is sufficient to meet the needs of both acute phase and the immune responses. Given that the acute phase response is likely to be a much larger consumer of during an infectious challenge than the immune system itself, future studies on the impact of poultry feed supplement should include measures of the adequacy acute phase response, such as production of acute phase proteins.

Animal nutrition and nutritional Immunity

The immune system coordinates a rapid flux of several poultry nutritional ingredients out of body fluids and into intracellular storage pools starving some types of pathogens. For example, transferring production by the liver increases dramatically during the acute phase response of broiler chickens and laying hens (Hallquist and Klasing, 1994). This iron binding protein mediates the transfer of iron out of blood plasma and into the liver where it is less available to pathogens. Feeding high levels of EDTA to chicks increases the deposition of iron into tissues and increases plasma concentrations. This predisposeschicks to increased mortality following a challenge with Escherichia coli (Tufft and Nockels, 1991). A redistribution of zinc is mediated by interleukin (IL)-1 during the acute phase response, due to enhanced synthesis of hepatic metallothionein (Klasing, 1984), however it is not clear if this is important in limiting the availability to pathogens in animal nutrition. Avidin is secreted by stimulated chicken macrophages, suggesting that the sequestration of blotin aids in starving pathogens of biotin at the site of infections (Korpela, 1984).

Direct Regulatory Actions

An immune response requires extensive communication between a wide variety of cell types. They play important roles by modulating the release of communication molecules or by changing the reactivity of leukocytes to extracellular signals. Amongst poultry feed supplements polyunsaturated fatty acids (PUFA) provide a good influence in the immune system by affecting intercellular communication. The amount, type, and PUFA determines the types of fatty acids that are incorporated into cell membranes and consequently the fluidity of the membrane and the types of eicosanoids that are released as communication molecules (Korver and Klasing, 1995, 1997). Linoleic acid is a member of the n-6 series of PUFA and a principle fatty acid in cereal grains and soybeans. It is elongated to Arachidonic acid and incorporated into cell membranes, A phospholipase-dependent communication cascade causes the release of arachidonate and its conversion into metabolically active prostaglandins, leukotrienes, and thromboxanes. Similarly, in poultry nutrition n-3 PUFA can be incorporated into cell membranes. Upon release during cell signaling, the n-3 PUFA modify the amounts and types of eicosanoids that are produced causing changes in cell communication. In broiler chickens dietary fish oil, which is high in n-3 PUFA. modulates IL-1 and prostaglandin E (PGE) release during an inflammatory response. The modulatory effects of poultry nutrition in dietary n-3 fatty acids are reflected in increases in antibody responses to antigens but decreases in mitogen-induced proliferation of lymphocytes (Fritsche et al., 1991; Korver and Klasing 1997).

Physical and Chemical actions of Feeds

Feed accounts for 65-70% of the total costs in animal nutrition and production. Any operation must therefore have clear targets how to optimize feed efficiency and reduce feed cost and work daily towards those targets. The sharp rise in feed ingredient prices in general, and soy bean meal in particular has forced producers to refocus on what they spend on feeding, to raise efficiency targets and to go the extra mile for converting feed protein more efficiently into lean gain.

There exists a relation between dietary poultry feed supplements concentration and feed cost, performance and revenue. Both revenue and feed cost increase with higher poultry nutrition density in the diet (Waller, 2007). Thegreen zone marks the area with maximal difference between the revenue curve and feed cost curve. When setting the poultry nutrition levels in this range, the margin for 'revenue over feed cost' is highest. As feeding cost is a major production issue, this is also likely to represent the area with maximal net profit. A consistent production system with accurate data on animal nutrition and performance and carcass value are needed to fine tune the system. This basic information is available in most broiler operations, as bird genetics and the overall production system are well standardized. Many swine fattening farms also have such data available to define the poultry nutrition concentrations which are most suited for their genetics and the market conditions they operate under.

The intestines are the primary battleground between potential pathogens and the immune system. This is evidenced by the large number of pathogenic and nonpathogenic organisms located in the intestinal lumen (15 x 10"/kg body weight, Roitt, 1997), the focusing of host defenses along the intestinal epithelium (.e. the gut-associated lymphoid tissue). and the high incidence of entero-pathogenic diseases in all animals. The intestinal epithelium must maintain exceptionally high physical integrity to prevent the bulk transport of pathogens into the body, but it must be sufficiently thin to actively transport poultry nutrition. Physical and chemical attributes of the diet can modify the populations of microorganisms in the gastrointestinal tract, the capacity of pathogens to attach to enterocytes, and the integrity of the delicate intestinal epithelium.

Role of trace minerals in immunomodulation

A deficiency in one or more of these elements can compromise immunocompetence of an animal nutrition (Beisel, 1982; Suttle and Jones, 1989). The trace metals that have been associated with an improvement in immunity, or functions that support immunity, are Zinc, Manganese, Copper, and Selenium. The first level of defense in the immune system is the skin. Zinc and manganese are key elements for maintaining epithelial tissue integrity.

Zinc plays an important role in animal nutrition, particularly for layers, as a component of a number of metallo enzymes such as carbonic anhydrase which is essential for eggshell formation in the hen's shell gland. Other important zinc metalloenzymes in the hen include carboxypeptidases and DNA polymerases. These enzymes play important roles in the bird

immune response, in skin and wound healing, and for hormone production (testosterone and corticosteroids), Classic deficiency symptoms of a zinc deficiency in poultry nutrition could include a suppressed immune system, poor feathering and dermatitis, infertility and poor shell quality.

Selenium is an important constituent of the enzyme glutathione peroxidase. Glutathione peroxidase functions in the cell as its first line of defence against oxidation. Other selenoproteins in poultry nutrition play an important role in prevention of exudative diathesis, normal pancreatic function, and fertility. Levels of selenium as poultry feed supplement are limited by the FDA to only 0.30 ppm. Levels of selenium in feedstuffs for poultry nutrition can vary considerably dependent on soil content of selenium the crops are grown on. Often times, total selenium would reach levels of 0.40 to 0.50 ppm when corn and soybean levels are combined with 0.30 ppm levels. These high levels can to be beneficial to the immune status and performance of poultry flocks without being toxic. Dietary selenium works with Vitamin E in boosting the immune status in poultry nutrition.

Role of trace minerals in immuno modulation (Swine)

Trace minerals such as manganese, iron and zinc are essential for swine mineral as they are involved in many digestive, physiological and biological processes that directly affect fertility and health of sows and newborn pigs, and carcass quality of fattening pigs. When trace minerals are not provided in the proper levels, digestion. Immune system, hormone production, bone integrity and skin health can be seriously affected.

Several minerals are included in the regulation of the pig's immune system. The role of selenium in protecting biological membranes from oxidative degeneration was established many years ago (Lessard et al., 1991; Oldfield, 2003).

In animal nutrition dietary selenium is, therefore, necessary to obtain maximal immunity in pigs, but to avoid toxicity due to over the inclusion of selenium in diets fed to livestock is regulated by FDA and cannot exceed 0.3 ppm. However, recent research indicates that organic sources of selenium are better utilized by pigs than inorganic sources (Mahan and Parrett, 1996: Mahan et al., 1999). As a consequence, to obtain maximum improvements in the immune system, it may be advisable to use organic selenium, rather than inorganic sources of selenium.

Copper sulfate is usually added to nursery diets at concentrations between 150 and 250 ppm, although the poultry nutrition requirement for copper is much lower. Likewise, zinc oxide is often added to starter diets at levels of 2,000-4,000 ppm, which is much higher than the poultry nutrition requirement for zinc. However, the inclusion of these minerals at high concentrations in diets fed to nursery pigs has been shown to reduce scouring and to control post-weaning diarrhea without causing any toxicity symptoms (Poulsen, 1995; Goransson, 1997). These effects may be caused by the ability of zinc and copper to reduce concentrationsof coliform bacteria in the intestinal tract of weanling pigs (Namkung et al., 2006).

Role of vitamins in immunomodulation

Vitamin A: Low and very high poultry nutrition dietary vitamin A decreases body weight gain in broilers. Low poultry nutrition dietary vitamin A causes depression in vitro T-Lymphocytes responses and in vitro antibody production to defined protein antigens. Excess vitamin A intake also decreases immune responses. Maximum T-cell proliferative responses to antigen have been observed at vitamin A levels considerably above NRC (1984) recommended level. Vitamin A is required for intestinal absorption of zinc (Zn) in poultry nutrition while zinc influences vitamin A utilization by affecting retinol binding protein (RBP) synthesis and release from liver.

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Following primary immunization, the chickens deficient in vitamin A show the lowest antibody liter. The difference in antibody titer is the maximum on 7" day post-immunization. The supplementation in poultry feed supplement of Vitamin A either on the day of vaccination or few days afterwardsincreased antibody titer. It has been demonstrated that the optimum Hi titer against Newcastle disease was obtained when the feed contained 20,000 1.U. Vitamin A per kg of feed.

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Vitamin C: Under normal conditions, Vitamin C (Ascorbic acid) is synthesized in sufficient amounts by all species of poultry. However, under prolonged exposure to stress the ascorbic acid utilization may exceed the ability of chicken and turkeys to synthesize ascorbic acid. It is observed that ascorbic acid poultry feed supplement increases the HA level from 4 to 6 days post vaccination. The mechanism by which ascorbic acid ameliorates steroid mediated immuno-suppression is either by reducing adrenal synthesis of corticoids or by protecting the lymphoid tissues.

Vitamin D: Vitamin D is critical for proper bone development in poultry and enhancing poultry nutrition. Research has elucidated negative effects on broiler cellular immunity as affected by vitamin D deficiency (Aslam et al. 1998). In female broilers a diet devoid of vitamin D or a diet containing 800 IU/kg of cholecalciferol had depressed cellular immunity as measured by cutaneous basophil hypersensitivity response to phytohemagglutinin-P, depressed thymus weight, and depressed macrophage function. However, although SRBC is a T-dependent antigen, differences in primary or secondary responses did not occur (Aslam et al., 1998). Bio-chemical relationships. The supplementation of Vitamin E as poultry feed supplement in the diet of chicks enhances humoral immunity, which may be due to destruction of peroxides by vitamin E. Vitamin E and Se play a role in protecting against oxidative damage. Free radicals are scavenged by vitamin E as a first line of defense and then glutathione peroxidase of which Se is a part destroys any peroxides formed before they can damage the cell.

Vitamin E: Vitamin E enhances specific humoral and cell mediated immune responses as well as native resistance to disease, particularly phagocytosis levels of vitamin E have an immuno stimulatory effect, increase delayed hypersensitivity and affect mitogenic responsiveness. The Poultry feed supplement of Selenium at levels above those recommended as requirements (0.1 ppm) enhances the primary immune responses. Vitamin E and Se appear to participate in similar poultry nutrition and accordingly studies have been conducted with various levels of Se, vitamin E and their combinations to examine the effect on performance and immune response of broilers. Effect of poultry feed supplement of vitamin E, selenium and their combinations suggested that maximum body weight gain and best efficiency of feed utilization were observed in broilers fed diets containing 0.50 mg/kg Se and 300 IU/kg vitamin E Significantly higher antibody titres (HI and ELISA) at 10 day PI were attributed to 0.06 mg/kg and 150 IU/kg Se and vitamin E respectively. Hence, optimum growth and immune response may be achieved at  level of Se of 0.06 mg/kg and vitamin E at 150 IU/kg. The vitamin E level is higher than that recommended by NRC (1984, 1994),

Role of AA in immunomodulation

In animal nutrition Amino acids are required for the synthesis of a variety of specific proteins (including cytokines and antibodies) and regulate key metabolic pathways of the immune response to infectious pathogens. Adequate dietary provision of all amino acids is necessary for sustaining normal immuno-competence and protecting the bird from a variety of diseases. In commercial diets, Lysine is limiting behind TSAA Arginine ranges from third to fifth limiting depending on requirements and the ingredients used.

Branched-Chain Amino Acids

Bhargava et al. (1971a) conducted experiments measuring growth and antibody production to Newcastle disease virus in chickens fed various levels of Valine in both studies, Valine need for antibody production was higher than that of growth. In the subject of poultry nutrition Konashi et al. (2000) evaluated dietary reduction (50% of the control level) in the branched-chain amino acids and noted a reduction in the relative size of the thymus and bursa. The specific branched-chain amino acid that is most important for immune organ development (Valine, Isoleucine, or Leucine) in the former study is unknown because the 3 were reduced in the diet concomitantly.

Threonine

Threonine is an important limiting amino acid in livestock and in  poultry industry, which is often added to the feed as poultry feed supplement. Threonine is usually the second limiting amino acid for pig and the third for poultry. Like lysine, to which it acts as complementary, threonine is an essential amino acid for body protein deposition and growth. Thus, deficiency in threonine affects the utilization of lysine and consequently overall  animal nutrition status . Threonine is needed in gastrointestinal mucin production, and thereby involved in immune response. It has also been shown to improve livability of heat-stressed broilers (Lemme, 2001). Sanitary status, animals' environmental conditions and other factors of  animal nutrition impact the Threonine Lysine requirement.

Tryptophan

In animal nutrition sector It is essential amino acid & has emerged as a regulator of many immunological and physiological processes. Its plasma concentration declines in suffering from different illnesses and inflammations (induced or natural), suggesting an increased utilization of the amino acid in such instances (Le Floc'h et al., 2004). IBDV primarily impairs the humoral immune response which is followed by sever immune-suppression due to down regulation of T cells and macrophages.

Conclusion

Feed accounts for 65-70% of the total costs in animal nutrition industry . Any operation must therefore have clear targets to optimize poultry feed supplement requirements and reduce poultry feed supplement cost. The high density confinement rearing of birds with limited use of antibiotics has made it essential to find a solution for enhancement of immune response by poultry nutrition alteration. Not only does the immune system benefit directly from proper poultry nutrition, but indirectly proper poultry nutrition will also prepare the bird for periods of stress, reducing the adverse effects of stress and enhancing recovery from stressful periods.