NuPro in swine diets

Among the changes in agriculture in recent years are new rules applied to the feed industry, advances in animal genetics, and increased concern about animal welfare. In response to consumer demand, antibiotic growth promoters (AGPs) are no longer accepted in some countries, and it is expected that before long they will be banned worldwide.

Factors motivating the ban on AGPs include antibiotic cross-resistance, residues in meat, eggs, and milk, and the possible development of allergies in humans. There has been a similar trend toward elimination of animal protein sources (e.g., meat meal, meat and bone meal, plasma) from animal diets to prevent zoonotic infections (e.g., mad cow disease, salmonellosis).

For such reasons, there is a need for alternative products that promote growth and supply animals with protein sources without adversely affecting animal health and performance. One group of nutrients used as an alternative to animal protein sources is yeast extract, which is rich in several components, including nucleotides. Nucleotides participate in cell division, and consequently are involved in growth and immune response.

Metabolically, nucleotides take part in several essential processes (Lehninger, 1995), acting as precursors for nucleic acids (DNA, RNA), as a source of energy (ATP, ADP, AMP, GTP), as components of cofactors (FAD, NAD, NADP), and as participants in intracellular signaling systems (cAMP, cGMP) (Lerner and Shamir, 2000). Therefore, nucleotides have a role in a series of vital functions of the organism. The addition of nucleotides may help in intestinal health, bringing about a reduction in enteric diseases, especially in animals exposed to stressors such as the dietary and environmental changes experienced by weanling piglets.


Are nucleotides essential nutrients?

Widmaier et al. (2004) defined an essential nutrient as a substance required for normal or optimal body function, but synthesized by the body either not at all or in amounts inadequate to prevent disease. According to Grimble and Westwood (2000), nucleotides can be synthesized in the body. There is no biochemical reason why dietary nucleotides should be considered essential nutrients. Pathways for their synthesis or salvage are (with no exception) present in every tissue, and interorgan traffic should provide sufficient substrate for any tissue with increased requirement for DNA and RNA turnover.

Nevertheless, this model of metabolic complacency has been punctured by research that suggests that dietary nucleotide deficiency may impair liver, heart, intestinal and immune function. Interestingly, McDowell (1989) indicated in his book Vitamins in Animal Nutrition that yeast was one of the most important sources of vitamins in the beginning of the 20th century. The question now is: Was it only vitamins that caused improved health and performance? Although at that time nucleotides were not understood, they were nonetheless present in yeast and playing an important role.

A clear indication of the essentiality of nucleotides comes from Santiago, Chile. Brunser et al. (1994) supplemented a cow’s milk-based formula with nucleotides and observed a considerable reduction in diarrhea in children of low socioeconomic status, indicating improved immune response. Moreover, Cosgrove (1998) reported an improvement in height and weight gain of children fed formula supplemented with nucleotides. In fact, nucleotides have been used in commercial infant formula for many years.


Biochemical remarks

Grimble and Westwood (2000) summarized the main biochemical points of nucleotides. Pyrimidines and purines are synthesized de novo (at considerable energy cost) from simple molecules such as CO₂, ammonia, and ribose in the case of pyrimidines, or glycine, aspartate, and formyl and amine groups from folic acid and glutamine, respectively, in the case of purines.

Although nucleotide triphosphates can be formed directly via de novo synthesis, they may also be salvaged from the degradative pathway that occurs below the level of the nucleotide monophosphates. Similarly, utilization of dietary nucleotides by animals is also via a salvage pathway. Nucleotides can be synthesized from purine and pyrimidic bases.

The ratio of salvage to de novo pathway utilization may vary markedly among tissues (Grimble and Westwood, 2000). Those tissues with a heavy reliance on salvage are likely to be most affected by dietary nucleotide supply or by interorgan transfer. In addition, the ratio of salvage to de novo synthesis may change in individual organs in response to metabolic needs or according to organ or tissue function. Salvage or de novo enzymes can be expressed at different points in the cell cycle.


Distribution of nucleotides

The most well known biochemical role of nucleotides is related to immune function. However, nucleotides also play an important role in various tissues including skeletal muscle, cardiac, hepatic and intestinal.


IMMUNE SYSTEM

The tissues and cells of the immune system are extremely dynamic in their aggressive elimination of dangerous antigens and are coordinated and regulated, at least in part, by the cytokine network. Lymphocyte activation is accompanied by greatly increased nucleic acid synthesis.

The process of activation is managed by the lymphocyte in such a way that increases in de novo synthesis are minimized as a result of adaptive increases in salvage, efficiency of ribosome synthesis (Cooper, 1973), and storage (Harms-Ringdhal and Cooper, 1978). Therefore, in normal lymphocytes, there is a massive turnover of nucleic acids to service the rapid mitotic division that occurs in response to antigen stimulation (Westwood, 1999).


SKELETAL AND HEART MUSCLE

Synthesis of tRNA occurs at approximately the same rate as that of skeletal muscle protein. Loss of muscle ribosomes after an inflammatory stimulus reduces requirements for de novo/salvage pathways and requires increased salvage uptake during recovery to maintain adequate rates of RNA synthesis (Grimble and Westwood, 2000).

The heart depends on ATP (source of energy). Cardiac tRNA synthesis occurs at approximately 15% per day (Ray et al., 1973). It is likely that increases in nucleotide requirements are met via salvage pathways (Zimmer, 1996).


LIVER

On reviewing the literature, Grimble and Westwood (2000) concluded that the rRNA synthesis occurs at 12–25% per day and is slow compared with liver protein synthesis. The liver is uniquely adapted to rapid induction of a supply of nucleotides for RNA and DNA synthesis. Thus, in growing cultured hepatocytes, the log phase was associated with a marked increase in pyrimidine salvage. Surprisingly, purine salvage remained unaltered. The liver may be quite dependent on adequate salvage rates of pyrimidines.


INTESTINES

Detailed analysis of de novo and salvage pathways led Uddin et al. (1984) to conclude that rRNA synthesis in jejunal crypts was supplied mainly from pyrimidine salvage pathways and that synthesis declined with longitudinal cellular maturation. In contrast, incorporation of pyrimidines synthesized by de novo pathway into rRNA was low at all levels, however, it made an important contribution to mRNA synthesis.

Dietary nucleotides have been found to stimulate intestinal growth in young rats (Uauy et al., 1990), with supplementation of 0.8% nucleotides causing an increase in villus development and crypt depth, and increased protein and DNA in the intestine.


Inositol

Inositol is classified as a ‘conditionally essential’ nutrient. Combs (1998) describes the metabolically active form of myoinositol as phosphatidylinositol, which is thought to have several physiologically important roles. It acts as an effecter of the structure and function of membranes, as a source of arachidonic acid for eicosanoid production, and as a mediator of cellular responses to external stimuli. Under certain conditions, such as disturbed intestinal microflora, diets containing fat, or an external environment creating physiologic stress, animals can have needs for preformed myoinositol. Such a scenario is similar to that which is common among weanling piglets.


Use of NuPro®

NUTRITIONAL PROFILE OF NUPRO®

Nupro® (Alltech Inc.) is a yeast extract product rich in nucleotides, inositol, protein, glutamic acid, vitamins and minerals (Table 1). It is non-GMO, not of animal origin, and is available in large quantities – necessary qualities for many applications.


PRACTICAL RESPONSES IN PIGLETS

Mateo and Stein (2004) reported that a typical starter diet for weanling pigs has more 5′CMP, but less 5′AMP, 5′GMP, 5′IMP, and 5′UMP than the concentration found in sow milk. Therefore, it is beneficial to add nucleotides or nucleosides to such diets to improve immune response and intestinal health and thereby lessen enteric disease and improve performance.

Spring (2001) evaluated the use of NuPro® on performance and health of weanling pigs. The animals had diarrhea caused by E. coli. A total of 64 piglets (initial weight: 10 kg) were divided into two groups. The animals were fed a control diet and a diet in which NuPro® replaced 4% potato protein. Piglets fed NuPro® tended to have higher daily weight gain, higher feed consumption, and better feed conversion. The incidence of diarrhea was lower in the group fed NuPro®. Similarly, dietary supplementation with nucleotides (0.5%) was found to reduce the incidence of diarrhea in rats (Nuñez et al., 1990).

These results indicate that the use of NuPro® improves health and performance of swine. According to Uauy et al. (1994), nucleotides benefit the intestinal microflora, facilitating the growth of non-pathogenic microflora such as bifidobateria, which reduce intestinal pH due to their capacity to hydrolize sugar to lactic acid, which in turn, interferes with the growth of pathogenic bacteria. Besides bifidobacteria, Mateo et al. (2004) observed an increase in lactobacilli and a reduction in clostridia in feces of pigs fed a nucleoside-containing diet.

Furthermore, the intestine requires dietary nucleotides to maintain function (Grimble, 1994; Leleiko et al., 1983). Addition of nucleotides to the diet has been attributed with reducing bacterial translocation from the gastrointestinal tract (Adjei and Yamamoto, 1995), improving intestinal enzyme activity (Uauy et al., 1990), and increasing DNA, RNA, and protein content of intestinal mucosa (Leleiko et al., 1987; Uauy et al., 1990).

Carlson et al. (2005) studied the performance and intestinal morphology of pigs fed nursery diets supplemented with NuPro® or plasma protein. In the first experiment, pigs were assigned at weaning (day 0, 19 days of age) to one of three diets with or without carbadox (55 mg/kg). The control diet was used to create two other diets by addition of plasma or NuPro® at 5% (day 1 to day 14) or 2.5% (day 15 to day 28), respectively.

In the second experiment, pigs that received plasma protein, NuPro®, or control diets in the nursery (Experiment 1) were fed similar four-phase grower and finisher diets without antimicrobials, to market weight (day 130). Overall, daily gain and feed intake were higher in pigs fed nursery diets containing plasma protein or NuPro® compared with control pigs. On day 28, crypt depth, total intestinal wall thickness, villus width, and lamina propria area were smaller in pigs fed plasma protein or NuPro®.

Pigs fed NuPro® in the nursery diet had better daily gain to market weight than pigs that had been fed plasma protein or control diets. These results indicate that nursery pig growth performance was better when plasma protein or NuPro® were fed and subsequent grower and finisher performance was better in pigs fed NuPro® in the nursery, indicating that NuPro® is compatible with the pattern of enzyme secretion and ease of digestion that contributes to maximized performance in pigs post-weaning.

Weaning is a considerable challenge to the young piglet and represents a critical period in its life. It is also the period that establishes future growth and development. It is now well known that both the weight of the piglet at weaning and its growth rate in the 7–10 day period post-weaning influence subsequent growth rate and efficiency of feed utilization through to slaughter. From the investigation of Carlson et al. (2005), it can be concluded that NuPro® can be used as a growth promotant in nursery pigs instead of spray-dried plasma protein at 5% (Phase 1) or 2.5% (Phase 2), with or without inclusion of an antimicrobial feed additive.


Table 1. Nutritional composition of NuPro®.







Similarly, a field trial was conducted with piglets fed a standard diet containing 2% spray-dried plasma protein at a Brazilian swine company. Treatment diets were fed from 26 to 38 days of age: T1 – Control, T2 – NuPro® (1.5%), and T3 – pure nucleotides (2.5 kg/t). At 68 days of age, pigs fed diets containing NuPro® were heavier (T1 – 23.29 kg, T2 – 24.39 kg and T3 – 23.25 kg) and had lower mortality (T1 – 1.04%, T2– 0.66% and T3 –1.56%) compared with pigs fed the other two treatments.

Studies with NuPro® have also been conducted in poultry. Rutz et al. (2004) examined the performance of chicks fed NuPro® (2% of diet). Treatments consisted of feeding a control diet (T1), without addition of NuPro®, a diet containing NuPro® from 1 to 7 days of age (T2) and a diet containing NuPro® from 1 to 7 days and again from 38 to 42 days of age (T3). During the first week of life, birds fed NuPro® had higher feed consumption and body weight gain compared with birds fed the control diet. Birds fed NuPro® from 38 to 42 days of age had improved weight gain compared with birds fed NuPro® during 1 to 7 days of age only or birds fed control diets.

Qureshi (2002) evaluated leukocyte numbers and the macrophage activity in chicks fed diets containing graded levels (0, 2.5, 5.0 and 10%) of NuPro®. The author observed increases in leukocyte numbers and in the activity of macrophages when NuPro® was fed up to 5% of the diet. The effect of nucleotides on the immune system of several species is well documented (Grimble and Westwood, 2000).

In swine such a response could be important, especially at weaning (21–28 days of age), which is very stressful and coincides with a period in which maternal immunity is declining and the piglet has not yet formed its own immunity. Westwood (1999) stated that immune cells respond to rapid cell division to produce many identical clones. Therefore, in normal lymphocytes, there is a massive turnover of nucleic acids to service the rapid mitotic division that occurs in response to antigen stimulation. The efficiency of lymphocyte activation is sensitive to blood purines and pyrimidines that depend partly on dietary intake (Grimble and Westwood, 2000).


Conclusion

Nucleotides are crucial for the maintenance of animal health, especially during periods of rapid growth, sanitary challenge, injuries, and stress. Furthermore, nucleotides promote the growth of nonpathogenic bacteria, such as lactobacillus and bifidobacteria. Nucleotides can be synthesized through de novo or salvage pathways. De novo synthesis of nucleotides requires substantially greater amounts of metabolic energy compared with synthesis of nucleotides via salvage pathways.

NuPro® is a non-GMO product, not of animal origin, and is available in large amounts.

It is rich in nucleotides, protein, inositol, minerals and vitamins, and has a role in intestinal function and immune response. For these reasons, NuPro® offers an excellent alternative to animal origin feed sources and to antibiotic growth promoters.


References

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Authors: FERNANDO RUTZ, EDUARDO GONÇALVES XAVIER, JOSÉ LUIZ RECH, MARCOS ANTONIO ANCIUTI and VICTOR FERNANDO B. ROLL
Universidade Federal de Pelotas, Pelotas, RS, Brazil