Method for improving the nutritional status of immune-stressed animals

Abstract

Disclosed is a composition comprising β-glucan, yeast cell wall, direct-feeding microorganism (yeast+DFM) and L-carnitine, and a method of using the composition to improve nutritional status, growth performance and survival in animals by administering the composition to animals.Importantly, administering yeast+DFM in combination with L-carnitine results in synergistic restoration of insufficient levels of circulating vitamin A in animals.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Provisional Application No. 63 / 290,876, filed December 17, 2021, the entire contents of which are incorporated herein by reference.

[0002] FIELD OF THEINVENTION Compositions and methods of using the compositions for improving the nutritional status of animals are disclosed. [Background technology]

[0003] With an increasing population, the demand for food and food products from livestock is expected to increase significantly. In commercial pig farming operations, fast growing animals are more profitable and weight gain is directly affected by the nutritional status of the animals.

[0004] Specifically, in pigs, retinol nutritional status, as measured by serum concentration of vitamin A, is positively correlated with growth rate and viability in lactating pigs before weaning and in pigs after weaning. However, while dietary supplementation of nutrients such as vitamin A is sufficient based on nutritional requirements determined by the National Research Council (NRC; 2012), nutritional deficiencies still occur under immunological challenges, including but not limited to physical, psychological and environmental stresses, viral infections such as PRRS and SIV, and bacterial infections such as E. coli and Salmonella. Pigs respond to these immunological stresses by mounting an immune response (which redirects nutrients from growth to the immune system) and reducing feed consumption (which further reduces nutrient intake). These physiological responses cause nutritional deficiencies under immunological stress. In many cases, simply increasing dietary nutrient supply is not enough to overcome these challenges.

[0005] To address these challenges, feed additives are needed to restore vitamin A status and counter the negative effects on growth and viability of upregulating the immune system. Summary of the Invention

[0006] One aspect of the present disclosure includes a method for improving the nutritional status of a non-human animal undergoing immunological stress that requires improved nutritional status.The method includes orally administering to the animal a composition comprising β-glucan, yeast cell wall, direct-feeding microorganism (yeast+DFM) and L-carnitine, and improving the nutritional status of the animal includes restoring the animal's insufficient level of circulating vitamin A to a sufficient level of circulating vitamin A, and administering yeast+DFM in combination with L-carnitine results in a synergistic restoration of the animal's insufficient level of circulating vitamin A.

[0007] In some embodiments, an insufficient level of vitamin A is less than about 0.15 ppm and a sufficient level of vitamin A is greater than or equal to about 0.15 ppm, between about 0.15 ppm and about 0.2 ppm, or greater than or equal to about 0.2 ppm.

[0008] The animal may be an animal that is immunologically stressed in response to a challenge. In some embodiments, the animal is immunologically stressed in response to a stressor selected from microbial infection, induced inflammation (vaccination), emotional trauma (weaning) and physical trauma. In some embodiments, the animal is immunologically stressed in response to weaning. In some embodiments, the animal is immunologically stressed in response to vaccination.

[0009] The composition can be administered to animals at the beginning of weaning.In some embodiments, administering yeast+DFM in combination with L-carnitine to animals improves the growth and survival performance of animals.In some embodiments, growth performance includes ADG and feed conversion ratio.

[0010] In some embodiments, the animal is a pig. When the animal is a pig, the feed composition may contain yeast, DFM, and L-carnitine in the supplement at about 89%, about 1%, and about 10%, respectively. In some embodiments, the composition is administered in the feed composition at a content rate of about 0.3 lbs / ton to about 0.6 lbs / ton or at a content rate of about 0.9 lbs / ton to about 1.1 lbs / ton.

[0011] Another embodiment of the present disclosure includes a method for improving the growth and viability of an animal that requires improvement of growth and viability.The method includes orally administering to the animal a composition that includes β-glucan, yeast cell wall, direct-feeding microorganism (yeast+DFM) and L-carnitine, and the improvement of the growth and viability of the animal includes restoring the insufficient level of circulating vitamin A of the animal to a sufficient level of circulating vitamin A, and administering yeast+DFM in combination with L-carnitine results in synergistic restoration of the insufficient level of circulating vitamin A of the animal.In some embodiments, the animal is under immunological stress.

[0012] Further embodiments of the present disclosure include a method for reducing immunological stress in an animal in need of immunological stress reduction. The method includes orally administering a composition comprising β-glucan, yeast cell wall, direct-feed microorganism (yeast+DFM) and L-carnitine to the animal, and reducing the immunological stress of the animal includes restoring the animal's insufficient level of circulating vitamin A to a sufficient level of circulating vitamin A, and administering yeast+DFM in combination with L-carnitine results in synergistic restoration of the animal's insufficient level of circulating vitamin A. In some embodiments, the animal is immunologically stressed.

[0013] One aspect of the present disclosure includes a method for predicting the growth potential and viability of an animal. The method includes measuring the level of circulating vitamin A and correlating the level of circulating vitamin A with growth potential. The level of circulating vitamin A is positively correlated with growth potential and viability. [Brief description of the drawings]

[0014] The patent or application file contains at least one drawing in color. Copies of any color drawing(s) in this patent or patent application publication will be provided by the Office upon request and payment of the necessary fee.

[0015] [Figure 1] FIG. 1 is a plot showing serum vitamin A concentrations in pigs before and after weaning.

[0016] [Diagram 2] FIG. 2 is a plot showing the correlation between serum vitamin A and C-reactive protein concentrations at weaning.

[0017] [Diagram 3] FIG. 3 is a plot showing the change in serum vitamin A concentration in pigs before and after weaning according to dietary treatment.

[0018] [Figure 4] FIG. 4 is a plot showing the correlation between serum vitamin A and feed efficiency in growing pigs (60-200 lbs BW).

[0019] [Diagram 5] FIG. 5 is a plot showing the correlation between serum vitamin A and clearance rate in growing pigs (60-200 lbs BW).

[0020] [Figure 6] FIG. 6 is a plot showing the change in serum vitamin A concentration in fattening pigs fed all or part of the β-glucan / yeast cell wall / direct-fed microorganisms / L-carnitine Combo from weaning to the end of the fattening period. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0021] The present disclosure is based on the discovery that orally administering a composition comprising beta-glucan, yeast cell walls, direct-fed microorganisms (yeast+DFM) and L-carnitine to a non-human animal undergoing immunological stress improves the nutritional status, increases growth performance and reduces mortality in the non-human animal undergoing immunological stress.

[0022] Importantly, the inventors have surprisingly discovered that administering yeast+DFM in combination with L-carnitine to non-human animals undergoing immunological stress synergistically improves the nutritional status, growth performance and survival of the animals, as animals receiving yeast+DFM in combination with L-carnitine exhibit a higher level of improvement than would be expected if yeast+DFM or L-carnitine were administered separately.

[0023] I. Feed composition One aspect of the present disclosure includes a feed composition for non-human animals. The composition includes a basal animal diet supplemented with formulated yeast and "direct-fed microorganisms" (yeast + DFM) in combination with L-carnitine. The concentrations of yeast, DFM, and L-carnitine are 89%, 1%, and 10%, respectively, in the supplement.

[0024] (a) Direct Fed Microbial (DFM) As used herein, the term "direct-fed microorganisms" (DFM) is used to refer to live probiotic or prebiotic microorganisms that provide a health benefit when ingested by an animal.

[0025] As non-limiting examples, yeast DFMs include Saccharomyces bisporus, Saccharomyces boulardii, Saccharomyces cerevisiae, Saccharomyces capsularis, Saccharomyces delbrueckii, Saccharomyces fermentati, Saccharomyces lugwigii, Saccharomyces microellipsoides, Saccharomyces pastorianus, Saccharomyces rosei, and the like. rosei, Candida albicans, Candida cloaceae, Candida tropicalis, Candida utilis, Geotrichum candidum, Hansenula americana, Hansenula anomala, Hansenula wingei, and Aspergillus oryzae.

[0026] Non-limiting examples of bacterial DFM include Lactobacillus acidophilus, Bifedobact thermophilum, Bifedobacter longhum, Streptococcus faecium, Bacillus pumilus, Bacillus subtilis, Bacillus licheniformis, Lactobacillus acidophilus, Lactobacillus casei, Enterococcus faecium, Bifidobacterium bifidum, and the like. bifidium, Propionibacterium acidipropionici, Propionibacterium freudenreichii and Bifidobacterium pscudolongum.

[0027] The amount of DFM in the feed composition may vary depending on variables such as the DFM, the type of non-human animal receiving the feed composition, the weight, sex and health of the non-human animal, and can be determined empirically. Preferably, a DFM suitable for the feed composition of the present disclosure is Bacillus licheniformis. When the DFM of the feed composition is Bacillus licheniformis, the concentration of Bacillus licheniformis in the feed composition is about 1 x 10 1 cfu / g feed ~ approx. 1×10 10 cfu / g feed, approx. 1×10 1 cfu / g feed ~ approx. 1×10 6 cfu / g feed, approx. 1×10 5 cfu / g feed ~ approx. 1×10 10 cfu / g feed, or approximately 1 × 10 3 cfu / g feed ~ approx. 1×108 cfu / g feed. Preferably, the Bacillus licheniformis concentration is about 1 x 10 4 ~Approx. 1×10 6 cfu / g feed.

[0028] (b) Formulated Yeast As used herein, the yeast preparation may include a combination of Saccharomyces cerevisiae yeast extract, which comprises about 25-100% by weight of the total yeast preparation, hydrolyzed yeast, which comprises about 0-40% by weight of the total yeast preparation, and yeast culture, which comprises about 0-50% by weight of the total yeast preparation. The yeast preparation may also include limestone, which comprises about 0-50% by weight of the total yeast preparation.

[0029] The compounded yeast can be any yeast that is generally considered safe for use in food or pharmaceutical applications.Non-limiting examples of compounded yeast-derived products can include yeast cell wall-derived components such as β-glucans, arabinoxylan isomaltose, agarooligosaccharides, lactosucrose, cyclodextrin, lactose, fructooligosaccharides, laminariheptaose, lactulose, β-galactooligosaccharides, mannanoligosaccharides, raffinose, stachyose, oligofructose, glucosylsucrose, sucrose thermooligosaccharides, isomaltulose, caramel, inulin and xylooligosaccharides.In one embodiment, compounded yeast can include β-glucans and / or mannanooligosaccharides. Sources of yeast cell wall derived components include Saccharomyces bisporus, Saccharomyces boulardii, Saccharomyces cerevisiae, Saccharomyces capsularis, Saccharomyces delbrueckii, Saccharomyces fermentati, Saccharomyces ludwigi, Saccharomyces microellipsoides, Saccharomyces pastorianus, Saccharomyces rosei, Candida albicans, Candida cloaceae, Candida tropicalis, Candida utilis, Geotrichum candidum, Hansenula americana, Hansenula anomala, Hansenula winningei, and Aspergillus oryzae.

[0030] The yeast preparation may also contain bacterial cell wall-derived materials such as peptidoglycan and other components from gram-positive bacteria with high peptidoglycan content. Exemplary gram-positive bacteria include Lactobacillus acidophilus, Bifedobacter thermophilum, Bifedobacter longum, Streptococcus faecium, Bacillus pumilus, Bacillus subtilis, Bacillus licheniformis, Lactobacillus acidophilus, Lactobacillus casei, Enterococcus faecium, Bifidobacterium bifidum, Propionibacterium acidipropionici, Propionibacterium freudenreichii and Bifidobacterium pseudolongum.

[0031] The concentration of the formulated yeast in the feed composition of the present disclosure may vary depending on variables such as the formulated yeast, the type of non-human animal to which the feed composition is administered, the weight, sex and health of the non-human animal, and can be determined empirically. For example, the concentration of the formulated yeast in the feed composition may range from about 0.01 lbs / ton feed to about 1 lbs / ton feed, about 0.1 lbs / ton feed to about 2 lbs / ton feed, about 0.5 lbs / ton feed to about 1 lbs / ton feed, or about 0.1 lbs / ton feed to about 1 lbs / ton feed. In some embodiments, the concentration of the pepper product in the feed composition may range from about 0.3 lbs / ton feed to about 1.0 lbs / ton feed.

[0032] (c) Basal animal diet The basal animal diet suitable for the feed compositions of the present disclosure may vary depending on variables such as the target animal, the weight of the animal, and the developmental stage of the animal.

[0033] The terms "feed", "food" and "feed formulation" are used interchangeably herein and may refer to any feed composition that is typically fed to an animal. Basal animal diets that are typically fed to animals are known in the art. A basal animal diet may include one or more components of an animal feed. Non-limiting examples of feed substances or animal feed substances include corn or corn components, such as corn meal, corn fiber, corn hulls, corn DDGS (distillers dried grains with solubles), silage, ground corn, corn germ, corn gluten, corn oil, or other parts of a corn plant; soybeans or soybean components, such as soybean oil, soybean meal, soybean hulls, soybean silage, ground soybeans, or other parts of a soybean plant; wheat or wheat components, such as wheat meal, wheat fiber, wheat hulls, wheat hulls, ground wheat, wheat germ, or other parts of a wheat plant; rice or rice components, such as rice meal, rice fiber, rice hulls, rice hulls, ground rice, rice germ, or other parts of a rice plant; canola, such as canola oil, canola meal, canola protein, canola oil ... canola husk, ground canola, or other parts of the canola plant; sunflower or components of a sunflower plant; sorghum or components of a sorghum plant; sugar beet or components of a sugar beet plant; sugar cane or components of a sugar cane plant; barley or components of a barley plant; palm oil, palm kernel or components of a palm plant; glycerol; corn steep liquor; waste streams from agricultural processing facilities; lecithin; rumen protected fat; molasses; soybean molasses; flax; peanuts; peas; oats; grasses, such as orchard grass and fescue; fish meal, meat and bone meal; feather meal; and poultry by-product meal; and alfalfa and / or clover used for silage or hay, and various combinations of any of the feed ingredients described herein or other feed ingredients commonly known in the art.As will be appreciated in the art, the basal animal diet may be further supplemented with amino acids, vitamins, minerals, and other feed additives, such as other types of enzymes, organic acids, essential oils, probiotics, prebiotics, antioxidants, pigments, anti-caking agents, etc., as further described below. The basal animal diet may be formulated for administration to any animal subject, as further described below.

[0034] The basal animal diet may optionally contain at least one additional nutritional and / or pharmaceutical substance. For example, the at least one additional nutritional and / or pharmaceutical substance may be selected from the group consisting of vitamins, minerals, amino acids, antioxidants, probiotics, essential fatty acids, and pharma- ceutically acceptable additives. The composition may contain one additional nutritional and / or pharmaceutical component, or any combination of said additional components, in various amounts. Suitable examples of each additional component are detailed below.

[0035] A. Vitamins Optionally, the animal feed formulation may contain one or more vitamins.Vitamins suitable for use in dietary supplements include vitamin C, vitamin A, vitamin E, vitamin B12, vitamin K, riboflavin, niacin, vitamin D, vitamin B6, folic acid, pyridoxine, thiamine, pantothenic acid and biotin.Forms of vitamins include salts of vitamins, derivatives of vitamins, compounds with the same or similar activity as vitamins, and metabolites of vitamins.

[0036] The animal feed formulation may include one or more forms of effective amounts of any of the vitamins described herein or known in the art. Exemplary vitamins include vitamin K, vitamin D, vitamin C and biotin. An "effective amount" of a vitamin typically refers to an amount that is at least about 10% of the US Recommended Daily Intake ("RDA") of a particular vitamin for a subject. However, it is contemplated that an amount of a particular vitamin that exceeds the RDA may be beneficial for a particular animal. For example, the amount of a certain vitamin may exceed the applicable RDA by 100%, 200%, 300%, 400%, 500% or more.

[0037] B. Minerals Generally, animal feed formulations may contain one or more minerals or mineral sources.Non-limiting examples of minerals include, but are not limited to, calcium, iron, chromium, copper, iodine, zinc, magnesium, manganese, molybdenum, phosphorus, potassium and selenium.Suitable forms of any of the above minerals include soluble mineral salts, sparingly soluble mineral salts, insoluble mineral salts, chelated minerals, mineral complexes, non-reactive minerals such as carbonyl minerals and reduced minerals, and combinations thereof.

[0038] Generally speaking, an animal feed formulation may include one or more forms of an effective amount of any of the minerals described herein or known in the art. An "effective amount" of a mineral typically refers to an amount that is at least about 10% of the US Recommended Daily Intake ("RDA") of a particular mineral for a subject. However, it is contemplated that an amount of a particular mineral that exceeds the RDA may be beneficial to a particular subject. For example, the amount of a certain mineral may exceed the applicable RDA by 100%, 200%, 300%, 400%, 500% or more. Typically, the amount of a mineral included in a dietary supplement may range from about 1 mg to about 1500 mg, about 5 mg to about 500 mg, or about 50 mg to about 500 mg per dose.

[0039] C. Essential fatty acids Optionally, the animal feed formulation may include an essential fatty acid source. The essential fatty acid may be isolated or may be an oil or fat source containing the essential fatty acid. In one embodiment, the essential fatty acid may be a polyunsaturated fatty acid (PUFA) having at least two carbon-carbon double bonds, generally in a cis configuration. The PUFA may be a long-chain fatty acid having at least 18 carbon atoms. The PUFA is an omega-3 fatty acid in which the first double bond occurs at the third carbon-carbon bond from the methyl end of the carbon chain (i.e., opposite the carboxyl acid group). Examples of omega-3 fatty acids include α-linolenic acid (18:3, ALA), stearidonic acid (18:4), eicosatetraenoic acid (20:4), eicosapentaenoic acid (20:5, EPA), docosatetraenoic acid (22:4), n-3 docosapentaenoic acid (22:5, n-3 DPA), and docosahexaenoic acid (22:6, DHA). PUFA can also be an omega-5 fatty acid, in which the first double bond occurs at the fifth carbon-carbon bond from the methyl end. Representative omega-5 fatty acids include myristoleic acid (14:1), myristoleic acid ester, and cetyl myristoleate. PUFA can also be an omega-6 fatty acid, in which the first double bond occurs at the sixth carbon-carbon bond from the methyl end. Examples of omega-6 fatty acids include linoleic acid (18:2), gamma linoleic acid (18:3), eicosadienoic acid (20:2), dihomo-gamma linolenic acid (20:3), arachidonic acid (20:4), docosadienoic acid (22:2), adrenic acid (22:4), and n-6 ​​docosapentaenoic acid (22:5). The fatty acids can also be omega-9 fatty acids, such as oleic acid (18:1), eicosenoic acid (20:1), mead acid (20:3), erucic acid (22:1), nervonic acid (24:1).

[0040] In another embodiment, the essential fatty acid source can be oil from marine products. Marine products can be vertebrate fish or marine organisms, and oil can be fish oil or marine oil. Long-chain (20C, 22C) omega-3 and omega-6 fatty acids are found in marine products. The ratio of omega-3 fatty acids to omega-6 fatty acids in marine products ranges from about 8:1 to 20:1. Marine products from which oil rich in omega-3 fatty acids can be obtained include, but are not limited to, abalone, scallops, albacore tuna, anchovies, catfish, clams, cod, gemfish, herring, lake trout, mackerel, menhaden, orange roughy, salmon, sardines, mullet, sea bass, shark, shrimp, squid, trout and tuna.

[0041] In yet another embodiment, the essential fatty acid source can be an oil derived from a plant. Plant and vegetable oils are rich in omega-6 fatty acids. Some plant-derived oils, such as flaxseed oil, are particularly rich in omega-3 fatty acids. Vegetable oils or vegetable oils are generally extracted from the seeds of plants, but can also be extracted from other parts of plants. Vegetable oils commonly used for cooking or flavoring include acai oil, almond oil, amaranth oil, apricot seed oil, argan oil, avocado seed oil, babassu oil, ben oil, blackcurrant seed oil, Borneo taro nut oil, borage seed oil, buffalo pumpkin oil, canola oil, carob pod oil, cashew oil, castor oil, coconut oil, coriander seed oil, corn oil, cottonseed oil, evening primrose oil, camellia oil, flaxseed oil, grapeseed oil, hazelnut oil, and oleaginous oil. Examples of suitable vegetable oils include, but are not limited to, corn oil, hemp seed oil, kapok seed oil, lalemantia oil, linseed oil, macadamia oil, meadowfoam seed oil, mustard seed oil, okra seed oil, olive oil, palm oil, palm kernel oil, peanut oil, pecan oil, peki oil, perilla seed oil, pine nut oil, pistachio oil, poppy seed oil, prune kernel oil, pumpkin seed oil, quinoa oil, ramucil oil, rice bran oil, safflower, sesame oil, soybean oil, sunflower oil, tea oil, thistle oil, walnut oil or wheat germ oil. The vegetable-derived oils may also be hydrogenated or partially hydrogenated.

[0042] In yet another embodiment, the source of essential fatty acids can be derived from algae. Commercially available algae-derived oils include Crypthecodinium cohnii and Schizochytrium sp. Other suitable species of algae from which oil may be extracted include Aphanizomenon flos-aquae, Bacilliarophy sp., Botryococcus braunii, Chlorophyceae sp., Dunaliella tertiolecta, Euglena gracilis, Isochrysis galbana, Nannochloropsis salina, Nannochloris sp., Neochloris oleoabundans, Phaeodactylum tricornutum, and the like. tricornutum, Pleurochrysis carterae, Prymnesium parvum, Scenedesmus dimorphus, Spirulina sp. and Tetraselmis chui.

[0043] D. Amino Acids Animal feed formulations may optionally contain one to several amino acids. Suitable amino acids include alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine and valine, or their hydroxylated analogues. In certain embodiments, the amino acid is selected from essential amino acids. Essential amino acids are generally described as amino acids that cannot be synthesized de novo by organisms and therefore must be provided in the diet. As a non-limiting example, essential amino acids for humans include L-histidine, L-isoleucine, L-leucine, L-lysine, L-methionine, L-phenylalanine, L-valine and L-threonine.

[0044] E. Antioxidants Animal feed formulations may include one or more suitable antioxidants. As will be appreciated by those skilled in the art, the suitability of a given antioxidant will vary depending on the species to which the dietary supplement is administered. Non-limiting examples of antioxidants include ascorbic acid and its salts, ascorbyl palmitate, ascorbyl stearate, anoxomers, N-acetylcysteine, benzyl isothiocyanate, o-, m-, or p-aminobenzoic acid (o for anthranilic acid, p for PABA), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), caffeic acid, canthaxanthin, alpha-carotene, beta ... -caraotene), β-apocarotenic acid, carnosol, carvacrol, catechin, cetyl gallate, chlorogenic acid, citric acid and its salts, p-coumaric acid, curculin, 3,4-dihydroxybenzoic acid, N,N'-diphenyl-p-phenylenediamine (DPPD), dilauryl thiodipropionate, distearyl thiodipropionate, 2,6-di-tert-butylphenol, dodecyl gallate, edetic acid, ellagic acid, erythorbic acid, Sodium erythorbate, esculetin, esculin, 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline, ethyl gallate, ethyl maltol, ethylenediaminetetraacetic acid (EDTA), eugenol, ferulic acid, flavonoids, flavones (e.g. apigenin, chrysin, luteolin), flavonols (e.g. dathisitin, myricetin, daemfero), flavanones, fraxetin, fumaric acid, gallic acid, gentian extract , gluconic acid, glycine, guaiacum gum, hesperetin, α-hydroxybenzylphosphinic acid, hydroxycinnamic acid, hydroxyglutaric acid, hydroquinone, N-hydroxysuccinic acid, hydroxytyrosol, hydroxyurea, lactic acid and its salts, lecithin, lecithin citrate; R-α-lipoic acid, lutein, lycopene, malic acid, maltol, 5-methoxytryptamine, methyl gallate, monoglyceride citrate; monoisopropyl citrate;Morin, β-naphthoflavone, nordihydroguaiaretic acid (NDGA), octyl gallate, oxalic acid, palmityl citrate, phenothiazine, phosphatidylcholine, phosphoric acid, phosphate salts, phytic acid, phytyl bichromel, propyl gallate, polyphosphate salts, quercetin, trans-resveratrol, rosmarinic acid, sesamol, silymarin, sinapic acid, succinic acid, stearyl citrate, syringic acid, tartaric acid, thymol, tocopherols (i.e., α-, β-, γ-, and δ-tocopherol), tocotrienols (i.e., α-, β-, γ-, and δ-tocotrienol), tyrosol, vanillic acid, 2,6-di-tert-butyl-4-hydroxymethylphenol (i.e., Ionox 100), 2,4-(tris-3',5'-bi-tert-butyl-4'-hydroxybenzyl)-mesitylene (i.e. Ionox 330), 2,4,5-trihydroxybutyrophenone, ubiquinone, tert-butylhydroquinone (TBHQ), thiodipropionic acid, trihydroxybutyrophenone, tryptamine, tyramine, uric acid, vitamin K and its derivatives, vitamin Q10, zeaxanthin, or combinations thereof;

[0045] Natural antioxidants that may be included in the dietary supplement include, but are not limited to, apple peel extract, blueberry extract, carrot juice powder, clove extract, coffee berry, coffee bean extract, cranberry extract, eucalyptus extract, ginger powder, grape seed extract, green tea, olive leaf, parsley extract, peppermint, pimento extract, pomace, pomegranate extract, rice bran extract, rose hips, rosemary extract, sage extract, tart cherry extract, tomato extract, turmeric, and wheat germ oil.

[0046] F. Anti-inflammatory Drugs The animal feed formulation may optionally include at least one anti-inflammatory drug. In one embodiment, the anti-inflammatory drug may be a synthetic nonsteroidal anti-inflammatory drug (NSAID), such as acetylsalicylic acid, diclofenac, indomethacin, oxamethacin, ibuprofen, indoprofen, naproxen, ketoprofen, mefenamic acid, metamizole, piroxicam, and celecoxib. In another embodiment, the anti-inflammatory drug may be a prohormone that regulates the inflammatory process. Suitable prohormones with this property include prohormone convertase 1, proopiomelanocortin, prohormone B-type natriuretic peptide, SMR1 prohormone, and the like. In another embodiment, the anti-inflammatory drug may be an enzyme that has an anti-inflammatory effect. Examples of anti-inflammatory enzymes include bromelain, papain, serrapeptidase, and proteolytic enzymes, such as pancreatin (a mixture of trypsin, amylase, and lipase).

[0047] In yet another embodiment, the anti-inflammatory drug can be a peptide with anti-inflammatory effects. For example, the peptide can be an inhibitor of phospholipase A2, such as antiflamin 1, a peptide corresponding to amino acid residues 246-254 of lipocortin, antiflamin 2, a peptide corresponding to amino acid residues 39-47 of uteroglobin, S7 peptide that inhibits the interaction of interleukin 6 with the interleukin 6 receptor, RP1, a prenyl protein inhibitor, and similar peptides. Alternatively, the anti-inflammatory peptide can be cortistatin, a cyclic neuropeptide related to somatostatin, or an N-terminal fragment of SV-IV protein, a peptide corresponding to a conserved region of E-, L-, and P-selectin, and the like. Other suitable anti-inflammatory preparations include collagen hydrolysates and milk micronutrient concentrates (e.g., MicroLactin® available from Stolle Milk Biologics, Inc., Cincinnati, OH), as well as milk protein hydrolysates, casein hydrolysates, whey protein hydrolysates, and vegetable protein hydrolysates.

[0048] In a further embodiment, the anti-inflammatory agent can be a probiotic that has been shown to regulate inflammation.Suitable immunomodulatory probiotics include lactic acid bacteria, such as Lactobacillus acidophilus, Lactobacillus and Bifidobacterium.In yet another embodiment, the anti-inflammatory agent can be a plant extract with anti-inflammatory properties.Non-limiting examples of suitable plant extracts with anti-inflammatory effects include blueberry, boswellia, acacia catechu and scutellaria, celery seed, chamomile, cherry, devil's claw, eucalyptus, evening primrose, ginger, hawthorn fruit, horsetail, Kalopanax pictus bark, licorice root, turmeric, white clover, willow bark and yucca.

[0049] G. Medicinal Herbs The animal feed formulation may optionally include at least one herb or herb derivative. Suitable herbs and herb derivatives as used herein refer to, but are not limited to, herb extracts and substances derived from plants and plant parts, such as leaves, flowers and roots. Non-limiting exemplary herbs and herb derivatives include agrimony, alfalfa, aloe vera, amaranth, angelica, anise, barberry, basil, bayberry, bee pollen, birch, bistote, blackberry, black cohosh, black walnut, blessed thistle, blue cohosh, blue vervain, boneset, borage, buchu, buckthorn, ragweed, burdock, capsicum, cayenne, caraway, cascara sagrada, catnip, and the like. , celery, centaury, chamomile, chaparral, chickweed, chicory, chinchona, cloves, coltsfoot, comfrey, corn silk, couch grass, cramp bark, culver's root, siamese, cornflower, damiana, dandelion, devil's claw, dong quai, echinacea, elecampane, ephedra, eucalyptus, evening primrose, eyebright, false unicorn, fennel, fenugreek, fig, flaxseed, garlic , gentian, ginger, ginseng, goldenseal, gotu kola, gumweed, hawthorn, hops, holyhound, horseradish, horsetail, hyssop, hydrangea, hyssop, Iceland moss, Irish moss, jojoba, juniper, kelp, lady's slipper, lemongrass, licorice, lobelia, mandrake, marigold, marjoram, marshmallow, mistletoe, mullein, mustard, myrrh, nettle, oatstraw, Oregon grape , Papaya, Parsley, Passion Flower, Peach, Pennyroyal, Peppermint, Periwinkle, Plantain, Pluripotent Root, Pockweed, Prickly Ash, Psyllium, Queen of the Meadow, Red Clover, Red Raspberry, Redmond Clay, Rhubarb, Rose Hips, Rosemary, Rue, Safflower, Saffron, Sage, St. John's Wort, Sarsaparilla, Sassafras, Saw Palmetto, Skullcap, Senega, Senna, Shepherd's Purse,Slippery elm, spearmint, spikenard, squavine, stillingia, strawberry, taheebo, thyme, uva ursi, valerian, violet, watercress, white oak bark, white pine bark, wild cherry, wild lettuce, wild yam, willow, wintergreen, witch hazel, wood betony, wormwood, yarrow, yellow dock, yerba santa, yucca, and combinations thereof.

[0050] H. Pigment The animal feed formulation may optionally include at least one pigment. Suitable non-limiting pigments include actinoerythrin, alizarin, alloxanthin, β-apo-2'-carotenal, apo-2-lycopenal, apo-6'-lycopenal, astacein, astaxanthin, azafulinaldehyde, bacterioruberin, aixin, α-carotene, β-carotene, γ-carotene, β-carotenone, canthaxanthin, capsanthin, capsorubin, citranaxanthin, citroxanthin, crocetin, crocetin semialdehyde, crocin, and crutaxan. tin, cryptocapsin, α-cryptoxanthin, β-cryptoxanthin, cryptomonaxanthin, scinthiaxanthin, decaprenoxanthin, dehydroadonirubin, diadinoxanthin, 1,4-diamino-2,3-dihydroanthraquinone, 1,4-dihydroxyanthraquinone, 2,2'-diketospirilloxanthin, eschscholzxanthin, eschscholzxanthon, flexanthin, foliachrome, fucoxanthin, gazaniaxanthin, hexahydrolycopene, hopkinsiaxanthin, hydroxyxanthin Ferriodenone, isofucoxanthin, roloxanthin, lutein, luteoxanthin, lycopene, lycopersene, lycoxanthin, molindone, mutatoxanthin, neochrome, neoxanthin, nonaprenoxanthin, OH-chlorobactene, okenone, osilaxanthin, paracentrone, pectenolone, pectenoxanthin, peridinin, flexanthophyll, pheniconone, phenicopterone, phoenicoxanthin, physariene, phytofluene, pyroxanthininol, quinone, rhodopin, rhodopinal, rhodopinol, Examples of such carotenoids include rhodovibrin, rhodoxanthin, rubixanthon, saproxanthin, semi-α-carotenone, semi-β-carotenone, syntaxanthin, siphonaxanthin, siphonanein, spheroidene, tangeraxanthin, torularhodin, torularhodin methyl ester, torularhodin aldehyde, torulene, 1,2,4-trihydroxyanthraquinone, triphasiaxanthin, trolichrome, baukeliaxanthin, violaxanthin, wammingon, xanthin, zeaxanthin, α-zeacarotene, or combinations thereof.

[0051] I. Pharmaceutically Acceptable Drugs The animal feed formulation may optionally contain at least one pharma- ceutically acceptable drug. Suitable non-limiting pharma-ceutically acceptable drugs include drugs that are acid / alkali unstable, pH-dependent, or weak acids or bases. Examples of acid-labile drugs include statins (e.g., pravastatin, fluvastatin, and atorvastatin), antibiotics (e.g., penicillin G, ampicillin, streptomycin, erythromycin, clarithromycin, and azithromycin), nucleoside analogs (e.g., dideoxyinosine (ddI or didanosine), dideoxyadenosine (ddA), dideoxycytosine (ddC), salicylates (e.g., aspirin), digoxin, bupropion, pancreatin, midazolam, and methadone. Drugs that dissolve only at acidic pH include nifedipine, emonapride, nicardipine, amosulalol, noscapine, propafenoic acid, and nifedipine. Weak acid drugs include phenobarbital, phenytoin, zidovudine (AZT), salicylates (e.g., aspirin), propionic acid compounds (e.g., ibuprofen), indole derivatives (e.g., indomethacin), fenamic acid compounds (e.g., meclofenamic acid), pyrrolacic acid compounds (e.g., tolmetin), cephalosporins (e.g., cephalothin, cephalaxin, cefazolin, cephradine, cephapirin, cefamandole, and cefoxitin), 6-fluoroquinolones, and prostaglandins.Weak base drugs include adrenergic agonists (e.g., ephedrine, deoxyephedrine, phenylephrine, epinephrine, salbutamol, and terbutaline), cholinergic agonists (e.g., physostigmine and neostigmine), antispasmodics (e.g., atropine, methantheline, and papaverine), curare-like drugs (e.g., chlorisondamine), tranquilizers and muscle relaxants (e.g., fluphenazine, thioridazine, trifluoperazine, chlorpromazine, and triflupromazine), antidepressants (e.g., amitriptyline and nortriptyline), antihistamines (e.g., diphenazine, In another embodiment, the drug may be a biphosphonate or another drug used to treat osteoporosis. Non-limiting examples of biphosphonates include alendronate, ibandronate, risedronate, zoledronate, pamidronate, neridronate, olpadronate, etidronate, clodronate and tiludronate.Other suitable drugs include estrogen, selective estrogen receptor modulator (SERM) and parathyroid hormone (PTH) drugs.In yet another embodiment, the drug can be an antibacterial drug.Suitable antibiotics include aminoglycosides (e.g., amikacin, gentamicin, kanamycin, neomycin, netilmicin, streptomycin, and tobramycin), carbacephems (e.g., loracarbef), carbapenems (e.g., sertapenem, imipenem, and meropenem), cephalosporins (e.g., cefadroxil, cefazolin, cephalexin, cefaclor, cefamandole, cephalexin, cefoxitin, cefprozil, cefuroxime, cefixime, cefdinir, cefditoren, cefoperazone, cefotaxime, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, and ceftriaxone), macrolides (e.g., azithromycin, clarithromycin, dirithromycin, erythromycin, and troleandomycin), monobactams, These include penicillins (e.g., amoxicillin, ampicillin, carbenicillin, cloxacillin, dicloxacillin, nafcillin, oxacillin, penicillin G, penicillin V, piperacillin, and ticarcillin), polypeptides (e.g., bacitracin, colistin, and polymyxin B), quinolones (e.g., profloxacin, enoxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, and trovafloxacin), sulfonamides (e.g., mafenide, sulfacetamide, sulfamethizole, sulfasalazine, sulfisoxazole, and trimethoprim-sulfamethoxazole), and tetracyclines (e.g., demeclocycline, doxycycline, minocycline, and oxytetracycline). In another embodiment, the drug can be an antiviral protease inhibitor (e.g., amprenavir, fosamprenavir, indinavir, lopinavir / ritonavir, ritonavir, saquinavir, and nelfinavir). In yet another embodiment, the drug can be a cardiovascular drug.Examples of suitable cardiovascular drugs include inotropes (e.g., digitalis (digoxin), ubidecarenone, and dopamine), vasodilators (e.g., nitroglycerin, captopril, dihydralazine, diltiazem, and isosorbide dinitrate), antihypertensives (e.g., α-methyldopa, chlorthalidone, reserpine, syrosingopine, resinamine, prazosin, phentolamine, felodipine, propanolol, pindolol, labetalol, clonidine, captopril, enalapril, and lisonopril), beta-blockers (e.g., levobunol, lol, pindolol, timolol maleate, bisoprolol, carvedilol and butoxamine), calcium channel blockers (e.g. amlodipine, felodipine, nicardipine, nifedipine, nimodipine, nisoldipine, nitrendipine, lacidipine, lercanidipine, verapamil, gallopamil and diltiazem), monensin, avilamycin, salinomycin, narasin, dicraserol, tylosin, bacitracin, bacitracin zinc and anticoagulants (e.g. dipyrimadol).

[0052] J. Additives Various additives commonly used in animal feed formulations can be selected based on their compatibility with the active ingredient.Non-limiting examples of suitable additives include substances selected from the group consisting of non-effervescent disintegration agents, colorants, flavor improvers, oral dispersion agents, stabilizers, preservatives, diluents, compression agents, lubricants, excipients, binders, taste masking agents, effervescent disintegration agents, and any combination of these substances.

[0053] In one embodiment, the additive is a binder.Suitable binders include starch, pregelatinized starch, gelatin, polyvinylpyrrolidone, cellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamide, polyvinyloxoazolidone, polyvinyl alcohol, C12-C18 fatty acid alcohol, polyethylene glycol, polyol, sugar, oligosaccharide, polypeptide, oligopeptide, and combinations thereof.Polypeptide can be any sequence of amino acids ranging from about 100 daltons to about 300,000 daltons.

[0054] In another aspect, the additive can be an excipient.Suitable excipients include carbohydrates, inorganic compounds and polyvinylpyrrolidone.As non-limiting examples, excipients can be dibasic and tribasic calcium sulfate, starch, calcium carbonate, magnesium carbonate, crystalline cellulose, dibasic calcium phosphate, magnesium carbonate, magnesium oxide, calcium silicate, talc, modified starch, lactose, sucrose, mannitol and sorbitol.

[0055] The additives may include non-effervescent disintegrants. Suitable examples of non-effervescent disintegrants include starches such as corn starch, potato starch, pregelatinized and modified starches thereof, sweeteners, clays such as bentonite, crystalline cellulose, alginic acid, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pectin and tragacanth.

[0056] In another embodiment, the additive can be an effervescent disintegration agent. By way of non-limiting example, suitable effervescent disintegration agents include a combination of sodium bicarbonate and citric acid, and a combination of sodium bicarbonate and tartaric acid.

[0057] Additives may include preservatives. Suitable examples of preservatives include antioxidants such as a-tocopherol or ascorbic acid, and antibacterial agents such as parabens, chlorobutanol or phenol.

[0058] In another embodiment, the additive may include a diluent. Suitable diluents include pharma- ceutically acceptable sugars, such as sucrose, dextrose, lactose, microcrystalline cellulose, fructose, xylitol and sorbitol; polyhydric alcohols; starch; preformulated direct compression diluents; and mixtures of any of the above.

[0059] The additive may include flavoring agents. The flavoring agents incorporated in the outer layer may be selected from synthetic flavor oils and flavoring aromatics and / or natural oils, extracts from plants, leaves, flowers, fruits, and combinations thereof. By way of example, they may include cinnamon oil, wintergreen oil, peppermint oil, clover oil, hay oil, anise oil, eucalyptus, vanilla, lemon oil, orange oil, citrus oils such as grape and grapefruit oil, fruit essences including apple, peach, pear, strawberry, raspberry, cherry, plum, pineapple and apricot.

[0060] In another embodiment, additives may include sweeteners.As non-limiting examples, sweeteners may be selected from glucose (corn syrup), dextrose, invert sugar, fructose, and their mixtures (when not used as carrier); saccharin and its various salts, such as sodium salt; dipeptide sweeteners, such as aspartame; dihydrochalcone compounds, glycyrrhizin; stevia (stevioside); chloro derivatives of sucrose, such as sucralose; sugar alcohols, such as sorbitol, mannitol, syritol, etc.

[0061] In another embodiment, the additive can be a lubricant. Suitable non-limiting examples of lubricants include magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, Sterotex, polyoxyethylene monostearate, talc, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and light mineral oil.

[0062] The additive may be a dispersing aid. Suitable dispersing agents may include starch, alginic acid, polyvinylpyrrolidone, guar gum, kaolin, bentonite, refined wood cellulose, sodium starch glycolate, isoamorphous silicate and crystalline cellulose as emulsifying surfactants with high HLB.

[0063] Depending on the embodiment, it may be desirable to provide a colorant in the outer layer. Suitable color additives include Food, Drug, and Cosmetic Colorants (FD&C), Drug, Cosmetic Colorants (D&C), or External Drug and Cosmetic Colorants (Ext. D&C). These colorants or dyes, along with corresponding lakes and certain natural and derived colorants, may be suitable for use in the present invention depending on the embodiment.

[0064] The additives may include taste masking agents. Taste-masking substances include, for example, hydroxypropyl ethers of cellulose (HPC), such as Klucel®, Nisswo HPC and PrimaFlo HP22; low-substituted hydroxypropyl ethers (L-HPC); hydroxypropyl methyl ethers of cellulose (HPMC), such as Seppifilm-LC, Pharmacoat®, Metolose SR, Opadry YS, PrimaFlo, MP3295A, Benecel MP824 and Benecel MP843; methylcellulose polymers, such as Methocel® and Metolose®; ethylcellulose (EC) and mixtures thereof, such as E461, Ethocel®, Aqualon®-EC, Surelease; polyvinyl alcohol (PVA), such as Opadry AMB; hydroxyethylcellulose, such as Natrosol®; carboxymethylcellulose and salts of carboxymethylcellulose (CMC), such as Aualon®-CMC; polyvinyl alcohol and polyethylene glycol copolymers, such as Kollicoat®. IR®; monoglycerides (Myverol), triglycerides (KLX), polyethylene glycol, modified food starch, acrylic polymers and mixtures of acrylic polymers and cellulose ethers such as Eudragit® EPO, Eudragit® RD100 and Eudragit® E100; cellulose acetate phthalate; sepifilm, such as a mixture of HPMC and stearic acid, cyclodextrin, and mixtures of these materials. In other embodiments, further contemplated taste-masking materials are those described in U.S. Patent Nos. 4,851,226; 5,075,114; and 5,876,759, each of which is incorporated herein by reference in its entirety.

[0065] In various embodiments, the additive may include a pH adjuster. In certain embodiments, the pH adjuster may include sodium carbonate or sodium bicarbonate.

[0066] The amounts and types of ingredients (i.e., metal chelates, chondro protectants, vitamins, minerals, amino acids, antioxidants, yeast cultures, and essential fatty acids) and other additives useful in animal feed formulations are described herein and throughout the examples.

[0067] II. Feed additive composition One aspect of the present disclosure includes a feed additive composition for a non-human animal. The composition includes a basal animal diet supplemented with formulated yeast and "direct-fed microorganisms" (yeast+DFM) in combination with L-carnitine. Other optional additives may be further included. The feed additive composition may be added to the basal animal diet for administration to the non-human animal. The feed additive composition may be combined with the basal animal diet to produce a feed composition as described in Section I.

[0068] The amount of the formulated yeast in the feed additive composition may vary depending on the type, weight, sex, and health condition of the non-human animal to which the formulated yeast, the feed additive composition containing the formulated yeast, and the feed additive composition are administered. In general, the feed additive composition may contain about 30% to about 95% of the formulated yeast, about 40% to about 90% of the formulated yeast, or about 55% to about 90% of the formulated yeast. In some embodiments, the feed additive composition may contain about 88% to about 90% or about 89%.

[0069] The amount of DFM in the feed additive composition of the present disclosure can range from about 0.05% to about 15%, from about 0.1% to about 10%, from about 0.5% to about 5%, from about 0.9% to about 1.1%. In some embodiments, the amount of DFM in the feed additive composition of the present disclosure ranges from about 0.9% to about 1.1%.

[0070] The amount of L-carnitine in the feed additive composition of the present disclosure is 10%, about 1% to about 20%, about 5% to about 15%, about 7% to about 13%, about 9% to about 11%. In some embodiments, the amount of L-carnitine in the feed additive composition of the present disclosure ranges from about 9% to about 11%.

[0071] In various embodiments, the feed additive composition can be introduced into the basal animal diet in various ways, depending on whether the feed additive composition is in liquid or solid form. Non-limiting examples of introducing the feed additive composition into the basal animal diet can be blending the feed additive composition into the basal animal diet, top dressing the basal animal diet with a solid composition, spraying the basal animal diet with a liquid feed additive composition, or combinations thereof. When introducing the feed additive into the basal animal diet, it is recognized that the amount of feed additive introduced into the basal animal diet is sufficient to provide a therapeutically effective amount of the combination of the formulated yeast and the capsicum product in the animal's diet.

[0072] In addition to yeast products, DFM and L-carnitine, the feed additive composition may further comprise at least one additional ingredient such as vitamins, minerals, amino acids, antioxidants, probiotics, etc., other than those that may be present in the DFM, essential fatty acids and pharma- ceutically acceptable additives. Such ingredients may be as described in Section I(e) above. In some embodiments, the feed additive composition further comprises rice hulls, mineral oil and calcium stearate.

[0073] III. How to use Another aspect of the present disclosure includes a method of using the feed composition. The method includes administering an animal feed composition or feed additive of the present disclosure to a non-human animal. In some embodiments, the feed or feed additive composition is orally administered to the non-human animal. The feed composition can be as described in section (I) and the feed additive composition can be as described in section (II) herein above.

[0074] In some embodiments, the non-human animal is immunologically stressed. The term "immunologically stressed animal" as used herein refers to a non-human animal that is stressed in response to inflammation or stressors, such as microbial infection, induced inflammation, such as from vaccination, emotional trauma, such as weaning, and physical trauma. Immunologically stressed animals generally have poor nutritional status, as measured by a lack of circulating vitamin A. Stressors and lack of vitamin A can lead to reduced growth performance and mortality in animals. Thus, in some embodiments, the method of the present disclosure includes improving the nutritional status of a non-human animal that is immunologically stressed. In some embodiments, the method of the present disclosure includes improving the growth and survival performance of the animal. In some embodiments, the method of the present disclosure includes reducing inflammation in the animal.

[0075] The timing and duration of administering the composition of the present invention to an animal can vary. The feed composition can be administered throughout the entire period of feeding the animal. Alternatively, the feed composition can be administered at a specific period during the growth and development of the animal. For example, the feed composition can be administered during periods when the animal is more susceptible to infection, such as infancy. The composition can also be administered after a microbial infection is detected and during the period of infection. The composition can also be administered at various intervals. For example, the composition can be administered daily, weekly, monthly, or over several months. In some embodiments, the composition is administered weekly. In other embodiments, the composition is administered monthly. In some embodiments, the composition is administered daily. As recognized in the art, the duration of treatment can vary depending on the growth and health of the animal.

[0076] (a) Non-human animals A non-human animal may be broadly defined as any animal that exhibits improved growth, improved health, improved intestinal health, and reduced microbial pathogen counts after administration of the feed additive composition. In various embodiments, the non-human animal may be a livestock mammal of different ages and health conditions. Non-limiting examples of suitable livestock mammals may be beef cattle, horses, dairy cows, veal calves, pigs, goats, sheep, bison, llamas, or alpacas. In other embodiments, the non-human animal may be a bird of different ages and health conditions. Non-limiting examples of suitable birds or poultry may be chickens, including meat chickens, laying hens, and breeding hens, ducks, game hens, geese, pheasants, guinea fowl, quail, turkeys, and ratites, such as emus and ostriches, and aquaculture. In another embodiment, the non-human animal may be a pet animal of different ages and health conditions. Non-limiting examples of pet animals may be dogs, cats, birds, hamsters, or guinea pigs. In some embodiments, the non-human animal is selected from the group including growing pigs, calves, foals, kids, cria, chickens, poultry, ducklings, baby dogs, kittens, or combinations thereof. In some embodiments, the non-human animal is a pig. In some embodiments, the non-human animal is an immunologically stressed pig. In some embodiments, the non-human animal is an immunologically stressed nursery pig.

[0077] (b) Improved Performance In some embodiments, the method includes using the feed additive to improve animal productivity. "Improved productivity" as defined herein refers to a positive change in size and / or maturity over a period of time in a non-human animal. In various embodiments, the non-human animal shows improved growth performance, including, for example, weight gain, feed intake, increased average daily weight gain (ADG), reduced feed conversion ratio (FCR), increased average daily food intake (ADFI), improved overall body weight, and F / G ratio (F / G ratio is defined as ADFI / ADG).

[0078] The non-human animals may exhibit a decrease in feed conversion rate of about 2% to about 5%, about 2% to about 5%, or about 3.0% or more compared to a control group not supplemented with the feed additive composition. The non-human animals may exhibit a decrease in mortality rate of about 0.5% to about 10%, about 1% to about 8%, about 1% to about 5%, or at least 2.0% or more compared to a control group not supplemented with the feed additive composition. The non-human animals may exhibit an improvement in weight gain, defined as the percentage of gain, of about 1% to about 10%, about 3% to about 5%, or at least 3.0%, compared to a control group not supplemented with the feed additive composition.

[0079] (c) Improved Health Yet another aspect of the present disclosure includes a method for improving the health of a non-human animal. As used herein, "improved health" refers to a reduction in the incidence of diarrhea, a reduction in the number of days with diarrhea, a reduction in mortality, improved gut health, a reduction in microbial pathogens in the intestinal tract of the animal, a reduction in a cytokine panel measuring TNF-α, a reduction in immunocrit levels, or a combination thereof, in a non-human animal compared to a control group.

[0080] (d) Reducing the impact of microbial pathogens Yet another aspect of the present disclosure includes a method of reducing the impact of a microbial pathogen in a non-human animal. Reducing the impact of a microbial pathogen includes improving gut health and reducing the microbial pathogen in the non-human animal. Reducing the impact of a microbial pathogen also includes improving the overall health and productivity of the non-human animal exposed to the microbial pathogen.

[0081] The term "microbial pathogen" as defined herein refers to a microorganism capable of causing disease. Infection is the invasion and proliferation of a pathogenic microorganism into a subject. Disease is the damage caused by infection to a vital function or system of a subject.

[0082] "Improved gut health" and "reduced microbial pathogens" refer to a reduction in pathogen numbers and reduced inflammation caused by microbial pathogens in a non-human animal compared to a control group. Non-limiting examples of pathogenic bacteria that can be controlled using the feed additive composition of the present disclosure include Clostridium perfringens, Eimeria maxima, Aeromonas hydrophila, Yersinia enterocolitica, Vibrio spp., Leptospira spp., Mycobacterium ulcerans, Listeria spp., pathogenic strains of E. coli, Pseudomonas spp., e.g. aeruginosa, Enterococcus spp., Salmonella spp., and the like. spp., Campylobacter spp., Staphylococcus spp. such as epidermidis, S. aureus (MRSA), M. smegmatis, Streptococcus sp., Clostridia and M. marinum.

[0083] In another preferred embodiment, reducing the impact of microbial pathogens comprises reducing the impact of C. perfringens in broiler chickens. In another embodiment, reducing the impact of microbial pathogens comprises controlling necrotic enteritis in chickens. In another embodiment, reducing the impact of microbial pathogens comprises controlling the impact of C. perfringens in combination with coccidiosis burden in diseased pullets.

[0084] definition Unless otherwise defined, all technical and scientific terms used herein have the meanings commonly understood by those skilled in the art to which this invention belongs. The following references provide those skilled in the art with general definitions of many terms used in this invention: Singleton et al., Dictionary of Microbiology and Molecular Biology (2nd ed. 1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The Glossary of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). The following terms used herein have the meanings ascribed to them unless otherwise specified.

[0085] When referring to elements of the disclosure or preferred embodiments thereof, the articles "a," "an," "the," and "said" are intended to mean that there are one or more elements. The terms "comprising," "including," and "having" are intended to be inclusive and mean that there may be additional elements other than the listed elements.

[0086] Since various modifications can be made in the cells and methods described above without departing from the scope of the present invention, it is intended that all matter contained in the above description and the following examples be interpreted in an illustrative and not a limiting sense. EXAMPLES

[0087] All patents and publications mentioned in this specification are indicative of the levels of those skilled in the art to which this disclosure pertains. All patents and publications are herein incorporated by reference to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference. The publications discussed throughout are provided solely for their disclosure prior to the filing date of the present application, and nothing herein is to be construed as an admission that the disclosure is not entitled to antedate such disclosure by virtue of prior invention.

[0088] The following examples are included to demonstrate the present disclosure. Those skilled in the art should understand that the techniques disclosed in the following examples represent the techniques that the inventor has discovered to work well in implementing the present disclosure. However, those skilled in the art will understand in light of the present disclosure that many changes can be made in the present disclosure and still obtain the same or similar results without departing from the spirit and scope of the present disclosure, and therefore all matters described should be interpreted as illustrative and not limiting.

[0089] Example 1. Increasing circulating vitamin A concentrations and improving growth performance in postweaned fattening pigs by feeding a combination of β-glucan / yeast cell wall / direct-fed microorganisms / L-carnitine (Combo) A study was conducted to evaluate the effect of feeding a combination of beta-glucan / yeast cell wall / direct-fed microorganisms / L-carnitine. A total of 36 pens were used in the study, with 27 mixed-sex pigs per pen. Pigs were weighed per pen upon arrival. Pens were divided into blocks by weight, and pens within blocks were randomly assigned to one of three dietary treatments in a randomized complete block design, with 12 pens per treatment (Table 1). [Table 1]

[0090] Combo analysis suggested that the concentrations of β-glucan, total glucan, and mannose were greater than 5.7%, 10.0%, and 9.0%, respectively. The concentration of DFM was 7.5 × 10 8 cfu / g preparation or less.

[0091] The study was conducted for 49 days in a four-stage feeding program immediately after weaning. The composition of the commercial control diets is shown in Table 2. Feed was provided through a FeedLogic® system, allowing feed intake data to be collected by pen.

[0092] Pigs were weighed by pen upon arrival and until the majority of the pens had completed their stage. On the same day that the pigs were weighed, the remaining feed in each pen was also weighed. Data from the FeedLogic® system was stored for each feeding event. The data was used to calculate the ADG, ADFI and F / G for each pen.

[0093] Blood samples were taken from two pigs per pen at four time points: 2 days before weaning in the sow unit and at 0 (immediately after weaning), 7 and 48 days in the fattening unit. Serum samples were stored at -20°C until analysis. A subjective fecal score for each pen was measured on days 3, 5 and 7 in fattening using a scale of 0=none, 1=mild, 2=substantial, 3=severe signs of diarrhea. [Table 2-1] [Table 2-2]

[0094] result: Part 1. Preweaning vaccination and weaning reduce circulating vitamin A concentrations Vaccination (PRRS / PCV2 / Mycoplasma) given to pigs 2 days before weaning in combination with the stress of the weaning process caused a 27% decrease (P<0.001) in serum vitamin A concentrations on the day of weaning (Figure 1). At 48 days after weaning, serum vitamin A concentrations gradually recovered to levels similar to those measured 2 days before weaning. In many cases, inadequate serum vitamin levels are considered a symptom of dietary / ingestion deficiencies. However, this is not always the case. In this and the following examples, vitamin A was added as retinol acetate to provide 8,819.4 IU / kg of dietary vitamin A, which was four times the required vitamin A concentration (2,200 IU / kg) for 5-25 kg fattening pigs by the National Research Council (NRC; 2012). The data suggest that serum vitamin A concentration at weaning is inversely correlated with serum C-reactive protein (CRP), one of the major acute phase proteins elevated in serum as a result of loading in pigs (Figure 2).

[0095] Part 2. Feeding a combination of β-glucan / yeast cell wall / direct-fed microorganisms / L-carnitine (Combo) restores circulating vitamin A concentrations after weaning As pigs recovered from postweaning immune stress, circulating vitamin A concentrations gradually recovered to levels similar to those measured preweaning (Figure 3). Data from a subset of sampled pigs suggest that compared with pigs fed the control and yeast + DFM treatments, pigs fed diets containing the combination of β-glucan / yeast cell wall / direct-fed microorganisms / L-carnitine (Combo) had the greatest increases in serum vitamin A concentrations from weaning to day 7 postweaning (38.4%) and from weaning to day 48 postweaning (64.3%; Table 3), respectively.

[0096] The increase in serum vitamin A concentration from weaning in pigs fed the yeast + DFM treatments was intermediate (25.8% and 60.1%, respectively). In addition, pigs fed the Combo treatment had a 20% significantly higher finisher ADG compared to pigs fed the control diet (0.76 vs. 0.64 lbs / day, P=0.01), whereas pigs fed the yeast + DFM treatment had only a slight improvement in pig ADG (0.73 vs. 0.64 lbs / day, P=0.10). [Table 3]

[0097] Distribution of vitamin A in serum was also evaluated. Pigs assigned to the Combo treatment started with the lowest percentage of pigs (95%) that were vitamin A sufficient (≥0.15 ppm) before weaning, but feeding Combo during fattening resulted in the highest percentage of pigs that were vitamin A sufficient at the end of the 49-day fattening period (95.2%) compared with the control and yeast + DFM treatments (95.0% and 91.7%, respectively; Table 4). At day 48, serum concentrations of CRP in pigs fed Combo were 21% lower than those fed the control diet (368.3 vs. 467.5 μg / ml, P = 0.10; Table 3). These data suggest that dietary supplementation with Combo efficiently restored circulating vitamin A concentrations after weaning, which represents the greatest recovery from the immune stress of weaning. [Table 4]

[0098] Part 3. Correlation between circulating vitamin A concentrations and pig growth performance Linear correlation analyses were performed to evaluate the correlation between serum vitamin A concentrations measured before and after weaning and individual pig growth performance during the fattening period (ADG and BW). Of 24 pairs of correlation analyses, numerically or significantly positive correlations were found (Table 5). In particular, serum vitamin A at weaning was positively correlated with pig ADG and BW throughout the remainder of the fattening period. Pig BW at the end of the fattening period was positively correlated with serum vitamin A before and after weaning (P<0.052). The high number of positive correlations between serum vitamin A and pig ADG / BW suggests that circulating vitamin A may be an indicator of performance. [Table 5]

[0099] Part 4. Feeding a combination of β-glucan / yeast cell wall / direct-fed microorganisms / L-carnitine (Combo) improved growth and survival performance of postweaned finishing pigs As shown in Table 6, when the productivity data of all pigs was analyzed, feeding the feed diet containing Combo resulted in significantly higher pig ADG and BW at the end of the 49-day feed phase compared to pigs fed the control diet (0.69 vs. 0.65 lbs / day, P<0.05, 45.5 vs. 43.4 lbs / day, P<0.05, respectively). Pigs fed yeast + DFM had intermediate ADG and BW, which were not significantly different from pigs fed the control treatment. In addition, feeding Combo and yeast + DFM resulted in lower mortality compared to the control treatment (1.85 vs. 3.41%). Pigs fed Combo also tended to require fewer individual antibiotic treatments compared to those fed the control diet (6.5 vs. 10.5%, P<0.10). These results suggest that feeding Combo improved pig growth and survival performance after weaning. [Table 6-1] [Table 6-2]

[0100] Example 2. Improving feed efficiency in growing pigs by feeding a combination of β-glucan / yeast cell wall / direct-fed microorganisms / L-carnitine (Combo) An 11-week trial was conducted to evaluate the effect of feeding Combo and Yeast + DFM to immunologically stressed growing pig groups on growth performance and viability. The immunologically stressed pig groups were characterized by PRRS and SIV positive and relatively high mortality and morbidity rates compared to production standards. Upon arrival, pigs (approximately 35 lbs) were distributed into pens containing 17-26 pigs per pen, with sex balance as close as possible. Pigs were fed a common diet until the start of the study approximately 2-3 weeks later. On day 1 of the study, pens were weighed and blocked by mean BW, and pens within blocks were randomly assigned to one of three dietary treatments (Table 7) in a randomized complete block design. This resulted in 11 pens per treatment for evaluation of growth performance and health. [Table 7]

[0101] Pigs were weighed per pen every 2 weeks (± 1 day) except between the shed top and run outs. When each pen was weighed, the remaining feed was measured. This allowed the calculation of ADG, ADFI and F / G per pen. The composition of the basal diet is shown in Table 8.

[0102] Blood samples were taken from two average-sized castrated pigs per pen prior to study initiation as baseline measurements. These sampled pigs were tagged for blood collection on days 32 and 76 after study initiation. Serum samples were stored at -20°C until analysis for vitamin A was performed. [Table 8-1] [Table 8-2]

[0103] result: Part 1. Feeding a combination of β-glucan / yeast cell wall / direct-fed microorganisms / L-carnitine (Combo) improved feed efficiency and survival in immunologically stressed growing pigs The results in Table 9 show that pigs fed Combo had a 5-point reduction in F / G at completion compared to pigs fed the control (2.22 vs. 2.27, P=0.28). However, pigs fed yeast + DFM showed no effect on feed efficiency. Furthermore, feeding Combo tended to reduce mortality (0.82 vs. 2.98%, P=0.09) and significantly reduced the total removal rate of poorly-healthy pigs (2.47 vs. 2.98%, P=0.04) compared to feeding the control diet. These results suggest that feeding Combo improved feed efficiency and survival in growing pigs undergoing immunological stress. [Table 9]

[0104] Part 2. Feeding a combination of β-glucan / yeast cell wall / direct-fed microorganisms / L-carnitine (Combo) improved circulating vitamin A concentrations, which correlated with better pig performance Serum vitamin A concentrations were evaluated for 22 pigs sampled per treatment on days 0 (baseline), 32, and 76 of the study (Table 10). Feeding Combo numerically improved serum vitamin A concentrations by 0.9% and 4.1% on days 32 and 76, respectively, compared to control. However, feeding yeast + DFM provided no improvement or only intermediate improvement. [Table 10]

[0105] A general linear model was performed using the mean of each treatment's completion F / G, total clearance rate and serum vitamin A. Serum vitamin A at day 32 was inversely related to pig F / G, as follows: F / G(BW 60-200 lbs)=-26.096 x serum vitamin A (D32) + 7.2606, R2=0.99 could be used to predict pig F / G using the formula (Figure 4). Serum vitamin A on day 76 was negatively correlated with the removal rate, and was calculated using the following formula: Total removal rate (%) = -480.75 x serum vitamin A (D76) + 101.26, R2 = 1.00 could be used to predict pig total removal rate (Figure 5). The strong linear correlation and predictability of serum vitamin A between pig F / G and removal rate suggests that serum vitamin A may be an indicator of productivity in growing pigs undergoing immunological stress. Feeding Combo improved the feed conversion ratio, nutritional status and health status of immunologically stressed pigs.

[0106] Example 3. Dose response of feeding a combination of β-glucan / yeast cell wall / direct-fed microorganisms / L-carnitine (Combo) to fattening and growing pigs To evaluate the dose response of feeding Combo to finishing pigs, high (1.0 lb / ton) and low (0.5 lb / ton) dietary concentrations of Combo were fed to weaner pigs in the study described in Example 1. In relatively healthy finishing pigs with no major health problems, feeding Combo at the low dose of 0.5 lb / ton resulted in better growth performance (Table 11) and a greater increase in serum vitamin A after weaning (Table 12) compared to feeding Combo at the high dose of 1.0 lb / ton. Feeding the high dose of Combo showed intermediate improvement compared to feeding the control treatment.

[0107] To evaluate the dose response of feeding Combo to growing pigs, high (1.0 lb / ton) and low (0.5 lb / ton) dietary concentrations of Combo were fed to growing pigs in the study described in Example 2. Feeding Combo at a low dose of 0.5 lb / ton resulted in better feed efficiency and survival in growing pigs undergoing immunological stress compared to feeding Combo at a high dose of 1.0 lb / ton (Table 13). The dose response of feeding Combo in fattening and growing pigs may depend on the health and immune status of the pigs. [Table 11-1] [Table 11-2] [Table 12-1] [Table 12-2] [Table 13]

[0108] Example 4. Feeding the full component combination of β-glucan / yeast cell wall / direct-fed microorganisms / L-carnitine (Combo) resulted in better growth performance, viability, and increased circulating vitamin A concentrations compared to feeding partial components to finishing pigs weighing 8-45 lbs. To evaluate the effect of dietary supplementation with all and some components of the Beta Glucan / Yeast Cell Wall / Direct-Fed Microorganisms / L-Carnitine Combination (Combo), a study was designed to feed finishing pigs weighing 8-45 lbs BW after weaning the dietary treatments shown in Table 14. Specifically, a total of 216 mixed-sex pigs were randomly placed into pens containing 27 pigs per pen at weaning. Pens were divided into blocks based on weaning weight, and pens within blocks were randomly assigned to one of four dietary treatments, with two pens per treatment. The study was conducted for 65 days immediately after weaning with a four-stage feeding program. The composition of the basal diet is shown in Table 15. Vitamin A was added as retinol acetate in a vitamin and trace mineral premix to provide 8,819.4 IU / kg of vitamin A in the diet, four times the recommended vitamin A concentration (2,200 IU / kg) for finishing pigs weighing 5–25 kg as recommended by the National Research Council (NRC; 2012).

[0109] Combo analysis suggested that the concentrations of β-glucan, total glucan, and mannose were greater than 5.7%, 10.0%, and 9.0%, respectively. The concentration of DFM was 7.5 × 10 8 cfu / g formulation. Dietary concentrations of β-glucan, yeast cell wall, DFM, and carnitine, when included in the diet, were the same for each treatment. [Table 14] [Table 15-1] [Table 15-2]

[0110] Serum samples were collected from two randomly selected pigs per pen (total of four pigs per treatment) at weaning (before ingestion of the experimental diets) and at the end of the fattening period when the pigs reached approximately 45 lb BW. Serum samples were analyzed for vitamin A concentration.

[0111] The results in Figure 6 show that the mean serum vitamin A concentration at weaning was 0.08 ppm, 47% lower than the adequate serum vitamin A level (0.15 ppm) described by R. Puls (1994). The nutritional vitamin A deficiency state at weaning is likely due to the immune stress experienced by the pigs during the weaning process. Pigs fed Combo had the highest serum vitamin A concentration at the end of fattening (0.541 ppm) compared to pigs fed the control (0.461 ppm), yeast / DFM (0.491 ppm) or carnitine (0.503 ppm) treatments. The increase in serum vitamin A concentration from weaning to the end of fattening was 117, 72, 114 and 140% for the control, yeast / DFM, carnitine and Combo treatments, respectively (Figure 6). Furthermore, feeding Combo improved serum vitamin A concentration range the most at the end of the fattening period (0.175-0.189 ppm) compared to all other treatments (Table 16). Except for the Combo treatment, the other three treatments all had minimum serum vitamin A concentrations below the sufficient level of 0.15 ppm at the end of the fattening period, suggesting that pigs may develop vitamin A deficiency despite being fed a vitamin A sufficient diet. These results suggest that dietary supplementation with Combo best restored vitamin A nutritional status after weaning compared to the control, yeast / DFM and carnitine treatments. [Table 16]

[0112] Restoring vitamin A status by feeding Combo to weaned pigs resulted in synergistic effects on growth and viability compared to feeding Combo components. Results in Table 17 suggest that feeding all Combo components improved finish ADG and finish G / F by 129% and 108%, respectively, compared to the control. These improvements were greater than the additive effects of feeding yeast / DFM (79% and 41%, respectively) or carnitine (29% and 29%, respectively) individually. Additionally, pigs fed all Combo components had the lowest mortality rate (P=0.14) compared to pigs fed Combo components and the control treatment. Improvements in viability appear to be greatest during the first 22 days after weaning when circulating vitamin A status is low due to immunological stress at weaning (Figure 6). [Table 17]

[0113] Example 5. Meta-analysis of feeding a combination of β-glucan / yeast cell wall / direct-fed microorganisms / L-carnitine (Combo) to 12-53 lb finishing pigs on growth performance and viability Three trials were conducted following the same procedure to evaluate feeding a combination of β-glucan / yeast cell wall / direct-fed microorganisms / L-carnitine (Combo) to weaned finishing pigs weighing 12-53 lbs on growth and viability. In each experiment, weaned pigs (starting BW=12.0±0.3 lbs) were housed in pens containing 27 pigs per pen and randomly assigned to either a control diet (Control) or a diet containing Combo at an inclusion level of 0.5 lbs / ton feed. This resulted in a total of 809 pigs in 30 pens in the control treatment group and 811 pigs in 30 pens in the Combo treatment across the three trials. Feed-grade pharmaceuticals, pharmacological levels of Zn (3,000 ppm) and Cu (150 ppm), were included in all trials.

[0114] The data in Table 18 suggest that consistent and repeated feeding of diets containing Combo at an inclusion level of 0.5 lb / ton feed to weaner pigs weighing 12-53 lbs BW improved pig growth and survival performance. Specifically, the growing ADG of pigs fed Combo improved by an average of 4.1% in each of the three studies compared to controls in the meta-analysis (0.76 vs. 0.73 lb / day; P<0.10). Growing feed conversion improved by an average of 1.2% in two of the three studies compared to controls (1.59 vs. 1.61; P=0.81). Increased ADG resulted in pigs fed Combo having an average of 1.3 lb heavier BW at the end of growing compared to controls (P=0.03). Additionally, total pigs removed (the sum of dead and stunted pigs) were reduced from 12.9% to 10.6% in the Combo treatment compared to the control (P=0.19), and medically treated pigs were reduced from 19.0% to 15.7% (P=0.10). This meta-analysis suggests that feeding Combo consistently and repeatedly improves survival and growth performance in finishing pigs weighing 12-53 lbs. These beneficial effects in finishing pigs are likely due to the restoration of vitamin A nutritional status after weaning as shown in the example above. [Table 18-1] [Table 18-2]

Claims

1. A method for improving the nutritional status of a non-human animal undergoing immunological stress in need of improved nutritional status, the method comprising orally administering to the animal a composition comprising beta-glucan, yeast cell walls, direct-fed microorganisms (yeast+DFM) and L-carnitine, wherein improving the nutritional status of the animal comprises restoring the animal's insufficient levels of circulating vitamin A to sufficient levels of circulating vitamin A, and administering the yeast+DFM in combination with L-carnitine results in a synergistic restoration of the animal's insufficient levels of circulating vitamin A.

2. 2. The method of claim 1, wherein the insufficient level of vitamin A is less than about 0.15 ppm and the sufficient level of vitamin A is greater than or equal to about 0.15 ppm, between about 0.15 ppm and about 0.2 ppm, or greater than or equal to about 0.2 ppm.

3. The method of claim 1, wherein the animal is undergoing immunological stress in response to a challenge.

4. 10. The method of claim 1, wherein the animal is immunologically stressed in response to a stressor selected from microbial infection, induced inflammation (vaccination), emotional trauma (weaning) and physical trauma.

5. The method of claim 1, wherein the animal is undergoing immunological stress in response to weaning.

6. The method of claim 1, wherein the animal is undergoing immunological stress in response to vaccination.

7. The method of claim 3, wherein the composition is administered to the animal at the onset of weaning.

8. 2. The method of claim 1, wherein administering yeast plus DFM in combination with L-carnitine to an animal improves the growth and survival performance of the animal.

9. 2. The method of claim 1, wherein the growth performance comprises ADG and feed conversion ratio.

10. The method of claim 1, wherein the animal is a pig.

11. 2. The method of claim 1, wherein the feed composition comprises yeast, DFM, and L-carnitine in the supplement in proportions of about 89%, about 1%, and about 10%, respectively.

12. 10. The method of claim 1, wherein the composition is administered at an inclusion rate of about 0.3 lbs / ton to about 0.6 lbs / ton or at an inclusion rate of about 0.9 lbs / ton to about 1.1 lbs / ton in a feed composition.

13. A method for improving the growth and viability of an animal in need thereof, the method comprising orally administering to the animal a composition comprising beta-glucan, yeast cell walls, direct-fed microorganisms (yeast+DFM) and L-carnitine, wherein improving the growth and viability of the animal comprises restoring the animal's insufficient levels of circulating vitamin A to sufficient levels of circulating vitamin A, wherein administering the yeast+DFM in combination with L-carnitine results in a synergistic restoration of the animal's insufficient levels of circulating vitamin A.

14. The method of claim 13, wherein the animal is subjected to immunological stress.

15. A method for reducing immunological stress in an animal in need thereof, the method comprising orally administering to the animal a composition comprising beta-glucan, yeast cell walls, direct-fed microorganisms (yeast+DFM) and L-carnitine, wherein reducing the immunological stress in the animal comprises restoring the animal's insufficient levels of circulating vitamin A to a sufficient level of circulating vitamin A, wherein administering the yeast+DFM in combination with L-carnitine results in a synergistic restoration of the animal's insufficient levels of circulating vitamin A.

16. The method of claim 15, wherein the animal is subjected to immunological stress.

17. A method for predicting the growth potential and viability of an animal, the method comprising measuring the level of circulating vitamin A and correlating the level of circulating vitamin A with growth potential, wherein the level of circulating vitamin A is positively correlated with growth potential and viability.

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