1. Introduction
Feed additives are materials that are administered to the animal to enhance the effectiveness of nutrients and exert their effects in the gut (Fuller, 2004). The use of antibiotics in animal nutrition, which has been practiced since the 1960s (Schiere and Tamminga, 1996). In addition to antibiotics, a wide variety of feed additives, many of biotechnological origin, are known to modify rumen fermentation. Among such additives are antibiotics, microbes (probiotics), and specific substrates like oligosaccharides (prebiotics) (Fuller, 2004). Moreover, due to advances in biotechnology, more effective enzyme preparations can now be produced in large quantities and relatively inexpensively (McDonald et al., 2010). Therefore, supplementation of the diet as a means of improving nutritive value is becoming commonplace.

Antibiotics are antimicrobial pharmaceutical, usually of plant or fungal origin and are also synthesized in the laboratory (Fuller, 2004). Although the primary use of antibiotics is in the treatment of infections, certain antibiotics are used as feed additives in order to improve growth and feed conversion efficiency. Among antibiotic groups are ionophores (McDonald et al., 2010) which are ion-bearing compounds, which surrounds cations so that the hydrophilic ion can be shuttled across hydrophobic cellular membranes to defeat the normal concentration gradient essential in living cells (Fuller, 2004). Ionophores display diverse structures and profiles of cation selectivity. For example, valinomycin is a cyclic peptide which binds potassium, while monensin is a carboxylic ionophore which displays a binding preference for sodium. Both can act as antibiotics. Ionophores are used in ruminant animals like cattle to improve feed efficiency by shifting rumen fermentation towards the production of more propionic acid, which can be used by the animal and less methane, which is lost. Ionophores hereby change the pattern of rumen microorganisms, reducing the production of acetate, butyrate and methane, and increasing the proportion of propionate (McDonald et al., 2010). Since methane is a waste product, the efficiency of rumen activity is improved. Ionophores also reduce the total mass of bacteria and thereby decrease the amount of dietary protein degraded. Avilomycin is licensed for use in pigs, broiler chickens and turkeys. Salinomycin is an ionophore available for use in pigs and also used to prevent coccidiosis in broiler chickens (Fuller, 2004).

McGuffey et al. (2001) also reviewed that ionophores have general metabolic role within the animal through improving production efficiency by providing a competitive advantage for certain microbes at the expense of others. In general, the metabolism of the selected microorganisms favors the host animal. In another report, broilers receiving the diet supplemented with antibiotic had significantly lower total aerobic bacterial counts in the small intestines compared to those on the other dietary treatments (Sarica et al., 2005) The combined supplementation of the antibiotic and enzyme resulted in a significantly lower E. coli concentration in the small intestines compared to the basal diet and the other dietary treatments.

As a result of advances in biotechnology, more effective enzyme preparations can now be produced in large quantities and relatively inexpensively (McDonald et al., 2010). Therefore, supplementation of the diet as a means of improving nutritive value is becoming commonplace. The enzymes used as food additives act in a number of ways. According to Fuller (2004), enzymes are mainly used in the diets of non-ruminants but are also added to ruminant diets. Their main purpose is to improve the nutritive value of diets, especially when poor-quality, and usually less expensive, ingredients are incorporated. Common example of enzymes is use of phytase feed enzyme in monogastric diets. Phytase feed enzymes have more general application as their substrate is invariably present in pig and poultry diets and their dietary inclusion economically generates bio-available phosphorous and reduces the phosphorous load on the environment. The prohibition of protein meals of animal origin, which also provide phosphorous, has accelerated the acceptance of phytase feed enzymes in certain countries (Fuller, 2004).

Amino acid digestibility may also be improved with phytase supplementation. In a study with finishing pigs, Zhang and Kornegay (1999) reported that the digestibility of all amino acids except proline and glycine increased linearly as phytase supplementation increased. In ruminant nutrition, enzymes improve the availability of plant storage polysaccharides (e.g. starch), oils and proteins, which are protected from digestive enzymes by the impermeable cell wall structures. Thus, cellulases can be used to break down cellulose, which is not degraded by endogenous mammalian enzymes. Enzymes are essential for the breakdown of cell-wall carbohydrates to release the sugars necessary for the growth of the lactic acid bacteria. Although resident plant-enzymes and acid hydrolysis produce simple sugars from these carbohydrates, addition of enzymes derived from certain bacteria, e.g. Aspergillus niger or Trichoderma viridi (Henderson et. al., 1982) increases the amount of available sugars. Commercial hemicellulase and cellulase enzyme cocktails are now available and improve the fermentation process considerably (Hooper et al 1989). However, prices of these products preclude their viability for farm level application, especially in developing countries. Supplementation of a wheat by-product diet with cellulase increased the ileal digestibility of non-starch polysaccharides from 0.192 to 0.359 and crude protein from 0.65 to 0.71(McDonald et al., 2010).

Complete digestion of complex ruminant feedstuffs such as hay or grain requires literally hundreds of enzymes. Enzyme preparations for ruminants are evaluated primarily on the basis of their capacity to degrade plant cell walls. Typically, these enzymes fall into the general classification of cellulases or xylanases (Renaville and Burny, 2001). However, most commercial preparations are not single gene products, containing a single enzyme activity. The diversity of enzyme activities within commercially available enzyme preparations is probably advantageous, in that a single product can target a wide variety of substrates Renaville and Burny (2001).

Probiotics and prebiotics
Probiotics are feed supplements that are added to the diet of farm animals to improve intestinal microbial balance (Fuller, 2004). In contrast to the use of antibiotics as nutritional modifiers, which destroy bacteria, the inclusion of probiotics in foods is designed to encourage certain strains of bacteria in the gut at the expense of less desirable ones (McDonald,2010). Besides, these microorganisms are responsible for production of vitamins of the B complex and digestive enzymes, and for stimulation of intestinal mucosa immunity, increasing protection against toxins produced by pathogenic microorganisms. In ruminants, they are more effective in controlling the diseases of the gastrointestinal tract of young animals, as there is no complication of the rumenmicro-flora. The initial colonization of the small intestine is from the dam's microflora and the immediate surroundings, and usually includes streptococci, E. coli and Clostridium welchii. When milk feeding commences, the lactobacilli become the predominant bacteria present. Calf probiotics contain benign lactobacilli or streptococci and are likely to be valuable only when given to calves that have suffered stress or have been treated with antibiotics that have destroyed the natural microflora (Fuller, 2004). Addition of probiotics to the diet produces variable benefit, depending on whether the animals are in poor health. It is also difficult to determine which bacterial species would be beneficial in any given circumstance. Probiotics have sometimes been found to be beneficial in protecting pigs from infectious diseases. Lactic acid bacteria isolated from the gastrointestinal tract of pigs, such as Enterococcus faecium and L. acidophilus, can inhibit enteric indicator strains, such as Salmonella enteritidis, S. cholera suis, S. typhimurium and Yersinia enterocolitica. Dry yeast (Saccharomyces cerevisiae) has the advantage over bacterial probiotics that it is more tolerant of extreme pH and environmental conditions. Probiotic use is subject to extensive legislation designed to protect farm animals and consumers. In adult ruminants yeasts may be used as probiotics to improverumen fermentation (Fuller, 2004).

Prebiotics are defined as non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and activity of one or a limited number of bacteria in the colon (Gibson and Roberfroid, 1995). The most common prebiotics are oligosaccharides, which are non-digestible carbohydrates. The way in which prebiotics act is by (1) supplying nutrients to beneficial microbes, or (2) tricking pathogenic bacteria into attaching to the oligosaccharide rather than to the intestinal mucosa. This reduces the intestinal colonization thereby decreasing the incidence of infection in the birds. Because the oligosaccharide is non-digestible, the microbes that are attached will travel along the GIT with the ingesta, and are excreted from the bird along with other undigested food.

Live microbial cultures and their extracts, particularly of Aspergillus oryzae and Saccharomyces cereuisiae, have been used as feed additives for many years. Their widespread use as manipulating agents for ruminal fermentation, socalled direct-fed microbials, is more recent, as are most of the research papers (Wallace and Newbold, 1992). The improved feed intake seems to be driven partly by an improved rate of fiber breakdown and partly by an improved duodenal flow of absorbable amino-nitrogen (Williams et al., 1990). These two observations are suggested to arise from a more active microbial population: the most reproducible effect of microbial feed additives is that they increase the viable count of anaerobic bacteria recovered from ruminal fluid. Increases of 50 to 100% are common (Wallace and Newbold, 1993), but increases of more than 10-fold compared with controls have been observed (Dawson et al., 1990). Cellulolytic bacterial numbers are increased (Wallace and Newbold, 1993) and lactic acidutilizing bacteria are stimulated by the dicarboxylic acids present (Martin and Nisbet, 1992), thus explaining in part the improvement in fiber breakdown and increased stability of the fermentation in animals receiving yeast and A. oryzae (Williams et al., 1991). Mehdi et al. (2011) reported that dietary inclusion of probiotic and prebiotic supported a superior performance of chicks and can be applied as antibiotic growth promoter substitutions in broilers diet.

Advances in understanding the regulation of nutrient use in agricultural animals have led to the development of technologies referred to as metabolic modifiers. Metabolic modifiers are a group of compounds that modify animal metabolism in specific and directed ways. They have the overall effect of improving productive efficiency (weight gain or milk yield per feed unit), improving carcass composition (lean:fat ratio) in growing animals, increasing milk yield in lactating animals, and decreasing animal waste per production unit (NRC, 1994). Two classes of compounds have received major focus: somatotropins (STs) and ß-adrenergic agonists. Somatotropin is a protein produced by the pituitary gland that differs slightly in structure among animal species. Thus, commercial application of STs depends on the use of recombinant DNA technology to produce the ST protein specific for a species. ßadrenergic agonists represent a class of compounds called phenethanolamines, and individual compounds differ in their biological effect. The several that affect animal growth are often referred to as repartitioning agents.

Beta-agonists are naturally occurring and synthetic organic compounds that share a common chemical structure of compounds classified as phenethanolamines. Several ß-agonists are used therapeutically in human and animal medicine for specific effects on smooth muscle, whereas others were investigated originally as possible antiobesity agents. Studies revealed that several ß-agonists act as metabolic modifiers with distinctive ability to repartition use of consumed nutrients toward increased skeletal muscle growth and decreased adipose tissue accumulation in growing cattle, swine, broilers, and turkeys (NRC 1994). Beta-agonists are orally active and efficacious at 5-30 parts per million (ppm) of feed when fed for short periods of time (28-42 d) near the end of the finishing period. Beta-agonists act directly through ß-adrenergic receptors on skeletal muscle and adipose cell membranes and generate signals that control metabolic activities in the cells. The rate of fat accumulation or growth in the animal slows, resulting in a leaner animal. The magnitude of these changes is influenced by the dose (amount) and the length of time the ß-agonist is consumed, the type of ß-agonist, and the target species (Beermann, 1993).

Skeletal muscle cells also contain ß-adrenergic receptors. Interaction of a ß-agonist with the receptor stimulates similar signaling pathways as in fat cells, altering muscle metabolism in a dose-dependent manner (Byrem, Beermann, and Robinson, 1996). Direct infusion of the ß-agonist cimaterol, a ß-agonist that has not been approved as a metabolic modifier, into the hind limb of growing steers increases the rate of amino acid extraction from the blood and results in increased rates of muscle protein synthesis and muscle growth (Byrem, Beermann, and Robinson 1998), independent of any systemic endocrine changes. Uncertainty remains regarding direct effects on protein turnover rates. The muscle growth enhancement results from hypertrophy (an increase in cell size) without any increase in cell number. The total number of muscle fibers in a muscle generally is set at birth in most domestic animal species. The changes that occur in skeletal muscle and adipose tissue are progressive over short periods of time, but they are not sustained over long periods because desensitization of receptors on target tissues occurs. For example, there is a marked down-regulation in adipose tissue of swine within 4 d after the commencement of feeding of Paylean (Dunshea and King 1995).Therefore, the recommended time of feeding is near the end of the finishing period. Longer feeding time has little or no effect on muscle or adipose tissue growth and would result in markedly decreased economic benefit.
Less energy per weight is required to grow muscle than to grow adipose tissue. Use of feed for growth in animals fed ß-agonists is more efficient overall.

Somatotropin is a naturally occurring protein hormone produced by the anterior pituitary gland and secreted into the blood circulatory system (Fuller,2004). Originally extracted and purified from pituitary glands, it is now available in much larger quantities due to the use of genetic engineering to enable bacterial production of human (HST), porcine (PST) and bovine (BST) somatotrophin. In pigs, it has been used to increase growth rate and lean carcass mass. In dairy cows, it is used to increase milk yield by as much as 40%. Somatotropin has several important roles in the regulation of development and growth of skeletal muscle, bone, adipose tissue, and the liver in growing animals. It plays an integral role in the coordination of lipid, protein, and mineral metabolism in livestock and other mammalian species. Elevation of ST in the circulation redirects nutrients toward increased muscle and bone growth and decreased adipose tissue growth in meat animals (Etherton and Bauman 1998). It also enhances milk production in lactating dairy cows (Bauman 1999). Efficiency of total body weight gain during growth and of milk production also is improved, resulting in decreased amounts of nutrients excreted per unit of meat and milk produced.

The amounts available using this technology were insufficient to allow scientists to use these technologies for investigations in large animals. Recombinant DNA technology was used in the early 1980s to produce the amounts needed for scientific investigations in food producing animals and is used today to accommodate commercial application. Its use has increased gradually to approximately one-fourth of the dairy cows in the United States. Field performance has demonstrated that increases in milk yield, milk fat, and milk protein were consistent each year in more than 350 herds and more than 800,000 cows administered bST during the first 4 yr after approval (Bauman et al. 1999). Porcine ST is not approved for use in the United States, but it is approved for use in 14 other countries (Dunshea et al. 2002).

The most commonly discussed ST is bovine somatotropin (bST), which has been administered to dairy cows to achieve increased milk yield, unprecedented improvements in productive fficiency (milk/feed), and decreased animal waste (Bauman, 1999). Experiences have demonstrated further that bST supplements result in marked improvements in productive efficiency while maintaining normal cow health and herd life (Etherton and Bauman 1998). Administration of pST to growing pigs results in greater nutrient use for lean tissue and less for body fat. This shift in nutrient partitioning results in substantially improved feed use, and the shift in lean:fat ratio represents an unprecedented improvement in carcass quality. Biological mechanisms that account for the effects of pST have been delineated and involve coordinated changes in lipid, protein, and carbohydrate metabolism (NRC, 1994). Improvements in dietary protein use efficiency with pST are especially significant and represent a decrease in the nutrient requirement per unit of lean tissue gain. Porcine somatotropin is undergoing testing required for FDA approval. Worldwide, pST is approved for commercial use in 14 countries. Supplements of ß-adrenergic agonists to growing animals improve feed use and increase the rate of weight gain, carcass leanness, and dressing percentage (NRC, 1994). Researchers have established that the mode of action involves changes in endocrine and cellular mechanisms (NRC, 1994). The net effect is that these repartitioning agents improve productive efficiency by modifying specific metabolic signals in a coordinated manner to increase nutrient use for lean tissue accretion.

Another key driver that will affect livestock nutrition is the need to mitigate greenhouse gas emissions. Improved feeding practices (such as increased amounts of concentrates or improved pasture quality) can reduce methane emissions per kilogram of feed intake or per kilogram of product, although the magnitude of the latter reduction decreases as production increases. Smith et al.(2007) suggested that many specific agents and dietary additives have been proposed to reduce methane emissions, including certain antibiotics, compounds that inhibit methanogenic bacteria, probiotics such as yeast culture and propionate precursors such as fumarate or malate that can reduce methane formation .Whether these various agents and additives are viable for practical use or not, and what their ultimate impacts could be on greenhouse gas mitigation, are areas that need further research. Improved feeding practices (such as increased amounts of concentrates or improved pasture quality) can reduce methane emissions per kilogram of feed intake or per kilogram of product, although the magnitude of the latter reduction decreases as production increases.

Considerable work is under way to address some of the issues associated with various antinutritional factors. These include methods to reduce the tannin content of tree and shrub material, the addition of essential oils that may be beneficial in ruminant nutrition and the use of other additives such as enzymes that can lead to beneficial effects on livestock performance. Enzymes are widely added to feeds for pigs and poultry, and these have contributed (with breeding) to the substantial gains in feed conversion efficiency that have been achieved. What are the prospects for the future? For the mixed crop-livestock smallholder systems in developing countries, there may be places where these will intensify using the inputs and tools of high-input systems in the developed world. In the places where intensification of this nature will not be possible, there are many ways in which nutritional constraints could be addressed, based on what is locally acceptable and available. One area of high priority for additional exploration, which could potentially have broad implications for tropical ruminant nutrition, is microbial genomics of the rumen, building on current research into the breaking down of lignocellulose for biofuels (NRC, 2009).

Another key driver that will affect livestock nutrition is the need to mitigate greenhouse gas emissions. Future international agricultural trade flows will be influenced by two sets of biotechnology-related factors. First, current and new government regulations, and bilateral and multilateral trade agreements; and, second, the behavior of private actors: private traders, farmers, and consumer demands and preferences (Pinstrup-Andersen, 1999). Future international agricultural trade flows will be influenced by two sets of biotechnology-related factors. First, current and new government regulations, and bilateral and multilateral trade agreements; and, second, the behavior of private actors: private traders, farmers, and consumer demands and preferences (Pinstrup-Andersen, 1999).

Additives used in animal nutrition, such as enzymes, probiotics, single-cell proteins and antibiotics in feed, are already widely used in intensive production systems worldwide to improve the nutrient availability of feeds and the productivity of livestock.

About Author / Additional Info:
Instructor of Animal Nutrition