JP2018537441A - A nutritional composition comprising LGG and a compound for stimulating the formation of food butyrate and / or endogenous butyrate - Google Patents

Abstract

Nutritional compositions comprising a combination of ingredients that stimulate butyrate production in the human intestine, such as Lactobacillus rhamnosus GG, a probiotic, food butyrate and / or a combination of polydextrose and galactooligosaccharides are provided. Further disclosed is a method of promoting tolerance to milk in a pediatric subject by providing said nutritional composition to the intended subject.
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Description

  The present disclosure relates generally to nutritional compositions comprising polydextrose (PDX), galactooligosaccharide (GOS) and Lactobacillus rhamnosus GG (LGG), or a combination of compositions comprising LGG and a food butyrate source. The nutritional composition is suitable for administration to pediatric subjects. Further disclosed is a method for reducing the risk of allergic sensitization / prevention of allergic diseases, promoting resistance to milk allergy and dietary management of food allergies by administering the compositions disclosed herein. The disclosed nutritional compositions can provide beneficial and beneficial health effects additively and / or synergistically.

  Food allergies such as allergies to milk protein, soy protein, rice protein and peanuts are a problem. Milk protein allergy (CMA) is the most common food allergy in early childhood and affects 2-3% of infants with immunoglobulin (IgE) and non-IgE-mediated syndromes. Food allergies continue to increase health concerns with increased morbidity and severity, potential increases in atopic diseases in later life, persistent risks, and functional gastrointestinal disorders. Therefore, there is a strong need to develop effective methods to support such allergy resistance.

  Typically, the first stage of treatment for CMA is rapid resolution of symptoms, and removal of milk protein from the diet is the only proven treatment. Certain hydrolyzed protein formulations have been used to circumvent CMA, but there is a need for nutritional compositions, particularly infant compositions, that contain ingredients that can further promote the acquisition of resistance to milk Has been.

  Accordingly, provided herein are nutritional compositions that promote tolerance to milk allergy. Further provided is a composition for food allergy diet management.

  Briefly, the present disclosure relates in one embodiment to a nutritional composition comprising a symbiotic combination of a prebiotic composition comprising PDX and GOS in combination with LGG. Furthermore, the present disclosure provides in one embodiment a nutritional composition comprising food butyrate and LGG. In some embodiments, the nutritional composition comprises ingredients that can stimulate the production of endogenous short chain fatty acids (SCFA), including butyrate in the human intestine. In some embodiments, the food butyrate may be provided directly by nutrition in the form of encapsulated butyrate or a concentrated lipid fraction from milk.

  The present disclosure further provides a method for promoting tolerance to milk allergy in a target subject by administering to the target subject a nutritional composition disclosed herein. Further provided is a method for dietary management of allergies, such as milk allergies, by administering to a target subject the nutritional composition disclosed herein.

  It is understood that both the foregoing general description and the following detailed description are intended to present embodiments of the present disclosure and to provide an overview or framework for understanding the nature and features of the present disclosure. I want. This description serves to explain the principles and operations of the claimed subject matter. Other and further features and advantages of the present disclosure will be readily apparent to those skilled in the art upon reading the following disclosure.

  Reference will now be made in detail to the embodiments of the present disclosure, one or more examples of which are set forth herein below. Each example is provided as an illustration of a nutritional composition of the present disclosure, but is not limited thereto. In fact, it will be apparent to those skilled in the art that various modifications and variations can be made to the teachings of the present disclosure without departing from the scope of the disclosure. For example, features illustrated or described as part of one embodiment can be used with another embodiment to obtain a further embodiment.

  Accordingly, the present disclosure is intended to embrace such modifications and variations that fall within the scope of the appended claims and their equivalents. Other objects, features and aspects of the present disclosure are disclosed in or are apparent from the following detailed description. It will be appreciated by those skilled in the art that this discussion is merely a description of exemplary embodiments and is not intended to limit the broader aspects of the present disclosure.

  The present disclosure relates generally to nutritional compositions comprising a probiotic comprising food butyrate and LGG. In some embodiments, prebiotics comprising PDX and GOS, and nutritional compositions comprising LGG are provided. Furthermore, the present disclosure relates to a method for promoting resistance to milk allergy or a method for dietary management of allergies in a target subject.

  “Allergy” as used herein is defined as “abnormal hypersensitivity to a substance that is normally accepted and generally considered harmless”. There are two basic stages in an allergic reaction. The first stage involves the development of an early stage of immediate hypersensitivity reaction to allergen. When an allergen first encounters the immune system, no allergic reaction occurs. Instead, the immune system prepares to encounter allergens in the future. Macrophages, which are scavenger cells, surround and degrade invading allergens. Macrophages then present allergen fragments on their cell walls to T lymphocytes, the main orchestrator of the body's immune response. This cognitive signal and some non-cognitive signals (eg cytokines) activate naive T cells and direct T cell differentiation to the T cell effector subpopulation. The main player of the allergy cascade is the Th-2 phenotype T cell (TH-2). TH-2 type T cells are characterized by the secretion of several cytokines including interleukin-4 (IL-4), IL-5 and IL-13. Cytokines IL-4 and IL-13 then activate B lymphocytes that produce antibodies of subclass E (IgE). IgE antibodies are directed against specific allergens. The interaction of specific IgE antibodies on the surface of effector cells (mast cells and basophils) with allergens triggers an early stage of immediate hypersensitivity.

  This activation of mast cells usually occurs within minutes after the second allergen exposure. IgE antibodies on mast cells constructed during the sensitization period recognize allergens and bind to invaders. When the allergen binds to the receptor, the mast cell granules release their contents. These contents or mediators are inflammatory substances such as histamine, platelet activating factor, prostaglandins, cytokines and leukotrienes. These mediators actually induce allergic attacks. Histamine stimulates mucus production and causes redness, swelling, and inflammation. Prostaglandins narrow the airways and enlarge blood vessels.

  The second stage of the allergic immune response is characterized by the infiltration of inflammatory cells such as eosinophils into the respiratory tract after allergen exposure. An important relationship between sensitization and inflammation is represented by T cells not only involved in IgE synthesis but also secrete mediators involved in eosinophil recruitment, activation and survival. Tissue mast cells and adjacent cells produce chemical mediators that help circulating basophils, eosinophils, and other cells migrate to the tissue and fight foreign bodies. Eosinophils secrete unique chemicals that sustain inflammation, cause tissue damage, and recruit more immune cells. This phase can occur anywhere from hours to days after allergen exposure and can last from hours to days.

  “Nutritional composition” means a substance or formulation that meets at least some of the nutritional requirements of a subject. The terms “nutrition (s)”, “nutritional preparation (s)”, “intestinal nutrition (s)” and “nutritional supplement (s)” Throughout this disclosure, it is used as a non-limiting example of a nutritional composition (s). Further, the “nutritional composition (s)” may be an intestinal formula, an oral formula, an infant formula, a pediatric formula, a pediatric formula, a growing-up milk, and / or an adult. A formula, liquid, powder, gel, paste, solid, concentrate, suspension, or ready-to-use form.

  “Pediatric subject” means a human under 13 years of age. In some embodiments, a pediatric subject refers to a human subject that is 8 years old from birth. In other embodiments, a pediatric subject refers to a human subject aged 1-6 years. In a further embodiment, a pediatric subject refers to a human subject aged 6-12 years. The term “pediatric subject” may refer to an infant (premature or full term) and / or a child, as described below.

  “Infant” means a human subject ranging in age from birth to 1 year of age and includes infants with an age adjusted to 0-12 months. The phrase “corrected age” refers to the infant's calendar age that reduced the amount of time the infant was born prematurely. Therefore, when the baby is held until full term, the corrected age is the age of the baby. The term infant includes low birth weight infants, very low birth weight infants, and preterm infants. “Early” means an infant born before the end of 37 weeks of gestation. “Maturity” means an infant born after the 37th week of pregnancy.

  “Child” means a subject in the range of 12 months to 13 years of age. In certain embodiments, the child is a subject between 1 and 12 years old. In other embodiments, the term “children” or “children” refers to a subject from 1 year to about 6 years old, or from about 7 years old to about 12 years old. In other embodiments, the terms “children” or “children” refer to any range of age from 12 months to about 13 years of age.

  “Infant formula” means a composition that meets at least some of the infant's nutritional requirements. In the United States, the content of infant formula is 21 C.I. F. R. Defined by federal regulations set forth in sections 100, 106 and 107.

  The term “medical food” refers to an enteral composition formulated or intended for dietary management of a disease or disorder. The medical food may be a food for oral intake or tube feeding (nasal gastric tube) and can be labeled for dietary management of a specific medical disorder, disease or condition, The nutritional requirements are clear and may be intended to use medical foods under medical supervision.

  As used herein, the term “peptide” describes a linear molecular chain of amino acids comprising a single chain molecule or fragment thereof. The peptides described herein contain no more than 50 total amino acids. Peptides can further form oligomers or multimers consisting of at least two identical or different molecules. Furthermore, peptidomimetics of such peptides in which amino acids and / or peptide bonds are replaced by functional analogs are also encompassed by the term “peptide”. Such functional analogs can include, but are not limited to, all known amino acids other than the 20 gene encoded amino acids such as selenocysteine.

  As used herein, the term “peptide” describes a linear molecular chain of amino acids comprising a single chain molecule or fragment thereof. The peptides described herein contain no more than 50 total amino acids. Peptides can further form oligomers or multimers consisting of at least two identical or different molecules. Furthermore, peptidomimetics of such peptides in which amino acids and / or peptide bonds are replaced by functional analogs are also encompassed by the term “peptide”. Such functional analogs can include, but are not limited to, all known amino acids other than the 20 gene encoded amino acids such as selenocysteine.

  The term “molar mass distribution” when used in reference to a hydrolyzed protein or protein hydrolyzate relates to the molar mass of each peptide present in the protein hydrolysate. For example, a protein hydrolyzate having a molar mass distribution greater than 500 daltons means that each peptide contained in the protein hydrolyzate has a molar mass of at least 500 daltons. Thus, in some embodiments, the peptides disclosed in Table 1 and Table 2 are derived from protein hydrolysates having a molar mass distribution greater than 500 Daltons. To produce a protein hydrolyzate having a molar mass distribution greater than 500 Daltons, the protein hydrolyzate is used to remove peptides, amino acids and / or other proteinaceous materials having a molar mass of less than 500 Daltons. It may be subjected to certain filtration procedures or any other procedure known in the art. For the purposes of this disclosure, any method known in the art can be used to produce a protein hydrolyzate having a molar mass distribution in excess of 500 Daltons.

  The term “protein equivalent” or “protein equivalent source” includes any protein source such as soybean, egg, whey or casein, as well as non-protein sources such as peptides or amino acids. Furthermore, the protein equivalent source may be any of those used in the art such as non-fat milk, whey protein, casein, soy protein, hydrolyzed protein, amino acid and the like. Useful milk protein sources for practicing the present disclosure include milk protein powder, milk protein concentrate, milk protein isolate, nonfat milk solid, skim milk, skim milk powder, whey protein, whey protein isolate, Whey protein casein, acid casein, casein salt (eg, sodium caseinate, calcium caseinate, calcium caseinate), soy protein, and any combination thereof are selected. In some embodiments, the protein equivalent source may include hydrolyzed proteins including partially hydrolyzed proteins and extensively hydrolyzed proteins. The protein equivalent source may, in some embodiments, include an intact protein. More particularly, the protein source comprises a) about 20% to about 80% of the peptide component described herein, and b) about 20% to about 80% of intact protein, hydrolyzed protein, or combinations thereof May be included.

  The term “protein equivalent source” also encompasses free amino acids. In some embodiments, the amino acids include, but are not limited to, histidine, isoleucine, leucine, lysine, methionine, cysteine, phenylalanine, tyrosine, threonine, tryptophan, valine, alanine, arginine, asparagine, aspartic acid, glutamic acid, glutamine, glycine, Proline, serine, carnitine, taurine and mixtures thereof. In some embodiments, the amino acid may be a branched chain amino acid. In certain other embodiments, small amino acid peptides can be included as the protein component of the nutritional composition. Such small amino acid peptides may be naturally occurring or synthesized.

  A “fractionation procedure” includes any process that divides a certain amount of a mixture into several smaller amounts known as fractions. These fractions may be different in composition from both the mixture and other fractions. Examples of fractionation procedures include, but are not limited to, melt fractionation, solvent fractionation, supercritical fluid fractionation, and / or combinations thereof.

  “Milk fat globule membrane” includes, but is not limited to, milk fat globule membrane protein, such as mucin 1, butyrophilin, adipophilin, CD36, CD14, lactadherin (PAS 6/7), xanthine oxidase and fatty acid binding protein, etc. Contains ingredients found in milk fat globule membrane. Furthermore, the “milk fat globule membrane” may contain phospholipids, cerebrosides, gangliosides, sphingomyelin and / or cholesterol.

  The term “glowing up milk” is a broad category of nutrition that is intended to be used as part of a variety of diets to support the normal growth and development of children aged about 1 to about 6 years of age. Refers to the composition.

  “Milk” means a component drawn or extracted from the mammary gland of a mammal. In some embodiments, the nutritional composition comprises dairy ingredients derived from livestock ungulates, ruminants or other mammals or any combination thereof.

  "Nutritionally complete" is the only nutritional supply that provides essentially all the required daily doses of trace elements in combination with vitamins, minerals and / or proteins, carbohydrates and lipids It means a composition that can be used as a source. In fact, “nutritionally complete” means the proper amount of carbohydrates, lipids, essential fatty acids, proteins, essential amino acids, conditional essential amino acids, vitamins, minerals, necessary to support the normal growth and development of the subject. And nutritional compositions that provide energy are described.

  A nutritionally complete nutrition composition for term infants, by definition, includes all qualitatively and quantitatively appropriate amounts of all carbohydrates, lipids, essential fatty acids, proteins, essential amino acids necessary for the growth of term infants. Provide conditional essential amino acids, vitamins, minerals, and energy.

  A nutritional composition that is “nutrientally complete” for a child, by definition, includes all qualitatively and quantitatively appropriate amounts of all carbohydrates, lipids, essential fatty acids, proteins, essential amino acids necessary for child growth. Provide conditional essential amino acids, vitamins, minerals, and energy.

  “Exogenous butyrate” or “food butyrate” refers to butyrate or butyrate derivatives that are intentionally included in the nutritional compositions of the present disclosure, rather than being produced in the intestine.

  “Endogenous butyrate” or “butyrate from an endogenous source” is not added as such, but is present in the intestine as a result of ingestion of the disclosed composition that is present as a result of other components or components of the composition. Refers to butyrate present. The presence of such other components or components of the composition stimulates intestinal butyrate production.

  The term “milk allergy” refers to food allergies, ie immune adverse reactions to one or more proteins contained in milk in human subjects. The main symptoms are gastrointestinal, dermatological, and respiratory symptoms. These can be converted into skin rashes, urticaria, vomiting, diarrhea, constipation and pain. The clinical spectrum covers various diseases such as anaphylactic reactions, atopic dermatitis, wheezing, infant colic, gastroesophageal reflux disease (GERD), esophagitis, colitis, gastroenteritis, headache / migraine, constipation.

  “Probiotic” means a low or non-pathogenic microorganism that has a beneficial effect on the health of the host.

  The term “non-viable probiotic” means a probiotic in which the metabolic activity or fertility of the reference probiotic is reduced or destroyed. More specifically, “non-viable” or “non-viable probiotic” means a non-viable probiotic microorganism, its cellular components and / or its metabolites. Such non-viable probiotics may have been sterilized by heat or otherwise inactivated. However, a “non-viable probiotic” refers to the cellular structure or other structures associated with the cell, such as exopolysaccharides and at least some of its biological glycol-protein and DNA / RNA structures at the cellular level. Retains and thus retains the ability to positively affect the health of the host. Conversely, the term “viability” means a living microorganism. As used herein, the term “non-viable” is synonymous with “inactivation”.

  A “prebiotic” is an indigestible food ingredient that favors the host by selectively activating the growth and / or activity of one or a limited number of bacteria that can improve the health of the host in the digestive tract. Means.

  The nutritional composition of the present disclosure may be any ingredient or selected as described herein as long as the remaining nutritional composition still contains all of the required ingredients or characteristics described herein. The starting material may not be substantially contained. In this context, and unless otherwise specified, the term “substantially free” includes any ingredient whose composition selected is less than a functional amount, typically less than 0.1% by weight. It is also meant to include 0 weight percent of any such or selected ingredients.

  All percentages, parts by weight and ratios used herein are by weight of the total composition unless otherwise specified.

  All references to unique features or limitations of the present disclosure are intended to include the corresponding pluralities or limitations unless otherwise indicated, or unless clearly indicated to the contrary by the referenced context, The reverse is also true.

  All combinations of methods or process steps used herein may be performed in any order, unless otherwise indicated, or unless the context clearly indicates the opposite, depending on the context in which the combination is referenced. it can.

  The methods of the present disclosure, and compositions comprising components thereof, of the embodiments described herein as well as any additional or optional ingredients described herein or useful in nutritional compositions. It may include, consist of, or consist essentially of essential elements and limitations.

  As used herein, the term “about” should be construed to refer to both numbers designated as the end point (s) of any range. Any reference to a range should provide support for any subset within that range.

  The present disclosure relates to a nutritional composition comprising butyrate and LGG. Non-limiting examples of butyrate as used herein include butyric acid, butyrate, and glycerol esters of butyric acid. The nutritional composition may further comprise a carbohydrate source, a protein source, and a fat or lipid source. In some embodiments, the nutritional composition may include an ingredient that can stimulate endogenous butyric acid production, and in other embodiments, the nutritional composition may include both food and endogenous butyrate. .

  The advantage of providing both exogenous and endogenous butyrate is to promote the acquisition of tolerance to milk. Furthermore, the advantage of providing both exogenous and endogenous butyrate with Lactobacillus rhamnosus GG (LGG) is to promote the acquisition of tolerance to milk. Traditional dietary management of milk allergies involves the use of formulations containing protein hydrolysates and amino acids rather than intact proteins. However, the inclusion of certain probiotics (eg, LGG) in combination with either endogenous or exogenous butyrate butyrate may contribute to promoting tolerance acquisition to milk.

  In some embodiments, the nutritional composition comprises a food butyrate source present in an amount of about 5 g / 100 kcal to about 500 g / 100 kcal. In some embodiments, the nutritional composition comprises a food butyrate source present in an amount of about 15 g / 100 kcal to about 450 g / 100 kcal. In some embodiments, the nutritional composition comprises a food butyrate source present in an amount of about 20 g / 100 kcal to about 400 g / 100 kcal. In some embodiments, the nutritional composition comprises a food butyrate source present in an amount of about 25 g / 100 kcal to about 350 g / 100 kcal. In some embodiments, the nutritional composition comprises a food butyrate source present in an amount of about 30 g / 100 kcal to about 280 g / 100 kcal.

  In some embodiments, the nutritional composition comprises about 0.01 g to about 10 g food butyrate per 100 g total fat in the nutritional composition. In some embodiments, the nutritional composition comprises about 0.1 g to about 8 g food butyrate per 100 g total fat in the nutritional composition. In some embodiments, the nutritional composition comprises about 0.4 g to about 7 g food butyrate per 100 g total fat in the nutritional composition. In some embodiments, the nutritional composition comprises from about 0.7 g to about 6.5 g food butyrate per 100 g total fat in the nutritional composition. In some embodiments, the nutritional composition comprises about 1.2 g to about 5.1 g food butyrate per 100 g total fat in the nutritional composition.

  In some embodiments, the food butyrate is a butyric acid; butyrate salt such as sodium butyrate, potassium butyrate, calcium butyrate, and / or magnesium butyrate; a glycerol ester of butyric acid; and / or a pharmaceutically acceptable base or acid. Are provided by one or more of the corresponding mixtures and corresponding salts, pure diastereomeric and enantiomeric forms or mixtures thereof.

  Food butyrate is provided by any suitable source known in the art. Animal source fats and derived products such as but not limited to milk, milk fat, butter, buttermilk, butter serum, cream, microbial fermentation derived products such as yogurt, fermented buttermilk, cheese, beverages, pineapples, And / or seed products derived from plants such as pineapple oil, apricot and / or apricot oil, barley, oats, brown rice, bran, mung beans, legumes, chlorophyll, apples, kiwi, oranges. In some embodiments, the food butyrate is produced synthetically. In embodiments where food butyrate is synthetically produced, the chemical structure of food butyrate may be altered as needed. Further, the synthesized food butyrate may be purified by any means known in the art to produce a purified food butyrate additive that can be incorporated into the nutritional compositions disclosed herein. it can. Food butyrate may be provided by dairy lipids and / or triglyceride-bound forms of butyrate.

  In some embodiments, the food butyrate may be provided in encapsulated form. In certain embodiments, food butyrate encapsulation can provide longer storage stability and can provide improved sensory stimulation properties of the nutritional composition. For example, in some embodiments, the food butyrate is mono- and di-glycerides, sugar and acid esters of glycerides, fat-derived materials such as phospholipids, starch, maltodextrin, gelatin, pectin, glucan, casein, It may be encapsulated or coated by the use or combination of plant, animal and microbial derived proteins and hydrocolloids such as soy protein and / or whey protein.

  Dietary butyric acid may also be provided in a coated form. For example, certain glycerol esters of butyric acid and / or amide derivatives of butyric acid, fat-derived substances such as mono- and diglycerides; sugar and glyceride acid esters; phospholipids; starch, maltodextrin, gelatin, pectin, glucan, casein, soybean Coating with protein and / or protein and hydrocolloid from plants, animals and microorganisms such as whey protein can improve the storage stability of dietary butyrate and the overall sensory stimulating properties of the nutritional composition Can be further improved.

  In certain embodiments, the food butyrate comprises a glycerol ester of butyric acid and / or an alkyl ester of butyric acid. Glycerol esters of butyric acid can provide minimal complexity when formulated and processed in nutritional compositions. Furthermore, glycerol esters of butyric acid can improve the shelf life of nutritional compositions containing food butyrate, and may have a lower impact on the sensory characteristics of the final product.

  In some embodiments, the food butyrate salt may include butyrate salts such as sodium butyrate, potassium butyrate, calcium butyrate, magnesium butyrate and combinations thereof. In some embodiments, use of selected food butyrate may improve intestinal health when provided to a target subject. In certain embodiments, the food butyrate comprises a suitable butyrate coated with one or more fats or lipids. In certain embodiments where the food butyrate comprises fat-coated butyrate, the nutritional composition may be a dry powder composition incorporating food butyrate.

  In some embodiments, the food butyrate salt may comprise any of the butyric acid compounds disclosed herein formulated to form a complex with chitosan or one or more cyclodextrins. For example, cyclodextrin is a cyclic oligosaccharide consisting of 6 (α-cyclodextrin), 7 (β-cyclodextrin) or 8 (γ-cyclodextrin) units of α-1,4-glucopyranose. Cyclodextrins are further characterized by a hydrophilic outer surface and a hydrophobic core. Without being bound by any particular theory, the aliphatic butyric acid chain forms a complex with the cyclodextrin core, increasing its molecular weight and thus reducing the volatility of the butyric acid compound. Thus, the bioavailability of food butyrate can be improved when the food butyrate comprises one or more cyclodextrins and a complex form of the butyric acid compound. In addition, cyclodextrins are bulky hydrophobic molecules that are resistant to gastric acid and gastrointestinal enzymes, and therefore administration of the butyric acid-cyclodextrin complex described herein facilitates the absorption of food butyrate in the small intestine. To do.

  In some embodiments, the food butyrate is provided from a concentrated lipid fraction derived from milk. For example, milk fat has a butyric acid content that is 20 times higher than the butyric acid content present in human milk fat. Furthermore, among short chain fatty acids (SCFAs) present in human milk, that is, fatty acids having a carbon chain length of 4 to 12, butyric acid (C4) is the most prevalent in milk. Thus, milk fat and / or a concentrated fraction of milk fat can be included in the nutritional composition to provide food butyrate.

  In embodiments where the food butyrate is provided by a milk-derived concentrated lipid fraction, the milk-derived concentrated lipid fraction can be produced by any number of fractionation techniques. These techniques include, but are not limited to, melting point fractionation, organic solvent fractionation, supercritical fluid fractionation, and any variants and combinations thereof.

  In addition, mixtures that can be subjected to fractionation operations to produce a concentrated lipid fraction include whole cow milk, cow cream, goat milk, sheep milk, yak milk and / or mixtures thereof. It is not limited to. In a preferred embodiment, the milk mixture used to produce the concentrated lipid fraction is milk.

  In addition to providing food butyrate, the concentrated lipid fraction comprises saturated fatty acids; trans fatty acids; branched chain fatty acids (BCFAs) including odd branched chain fatty acids (OBCFAs); conjugated linoleic acid (CLA); One of the components of milk fat globule membrane including unsaturated fatty acid; polyunsaturated fatty acid; cholesterol; phospholipid; milk fat globule membrane protein may be included.

In some embodiments, the concentrated lipid fraction is per 100 kcal,
From about 0.1 g to 8.0 g of saturated fatty acids;
From about 0.2 g to 7.0 g of a trans fatty acid;
From about 0.003 g to about 6.1 g of a branched chain fatty acid;
From about 0.026 g to about 2.5 g of conjugated linoleic acid;
From about 0.8 g to about 2.5 g of a monounsaturated fatty acid;
From about 2.3 g to about 4.4 g of a polyunsaturated fatty acid;
From about 100 mg to about 400 mg of cholesterol;
About 50 mg to about 400 mg phospholipid; and / or about 10 mg to about 500 mg milk fat globule membrane;
One or more of the above.

  The following examples illustrate milk fat content having a concentrated concentration of butyric acid (C4) that can be produced by a fractionation operation.

Example 1
The lipid profile of the fractionated milk fat produced by the supercritical carbon extraction fractionation method and the melt fractionation method is shown below.

  The nutritional composition of the present disclosure also includes at least one probiotic; in a preferred embodiment, the probiotic comprises LGG. In certain other embodiments, the probiotic is any Lactobacillus species, Bifidobacterium species, Bifidobacterium longum BB536 (BL999, ATCC: BAA-999), Bifidobacterium Longum AH1206 (NCIMB: 41382), Bifidobacterium breve AH1205 (NCIMB: 41387), Bifidobacterium infantis 35624 (NCIMB: 41003), and Bifidobacterium animalis subspecies lactis BB-12 (DSM No. 10140), or any combination thereof.

The amount of probiotic can vary from about 1 × 10 ⁴ to about 1.5 × 10 ¹² cfu probiotic (s) per 100 kcal. In some embodiments, the amount of probiotics can be from about 1 × 10 ⁶ to about 1 × 10 ⁹ cfu probiotic (s) per 100 kcal. In certain other embodiments, the amount of probiotic can vary from about 1 × 10 ⁷ cfu to about 1 × 10 ⁸ cfu / 100 kcal of probiotic (s) per 100 kcal.

  As described above, in a preferred embodiment, the probiotic comprises LGG. LGG is a probiotic strain isolated from healthy human intestinal flora. US Pat. No. 5,032,399 to Gorbach et al., Which is incorporated herein by reference in its entirety. LGG is resistant to most antibiotics, is stable in the presence of acid and bile, and greedyly adheres to mucosal cells in the human intestinal tract. Most people live 1-3 days, 30% of subjects up to 7 days. In addition to the ability to form colonies, LGG also has a beneficial effect on the mucosal immune response. LGG has been deposited with the depository agency American Type Culture Collection (ATCC) under the deposit number ATCC 53103.

  In one embodiment, the probiotic (s) can be viable or non-viable. Probiotics useful in this disclosure have been developed by genetic manipulation of organisms, whether naturally occurring, synthesized, or whether such sources are now known or later developed It may be a thing.

In some embodiments, the nutritional composition may include a source comprising a probiotic cell equivalent that refers to a level of non-viable, non-replicating probiotics equivalent to an equal number of viable cells. The term “non-replicating” should be understood as the amount of non-replicating microorganisms obtained from the same amount of replicating bacteria (cfu / g) containing inactivated probiotics, DNA fragments, cell walls or cytoplasmic compounds. In other words, the amount of non-viable non-replicating organisms is that all microorganisms are alive, whether they are dead, not replicating, inactivated or fragmented, etc. It is expressed by cfu as follows. When non-viable probiotics are included in the nutritional composition, the amount of probiotic cell equivalents is about 1 × 10 ⁴ to about 1.5 × 10 ¹⁰ cell equivalents of probiotics per 100 kcal. May vary). In some embodiments, the amount of probiotic cell equivalents can be from about 1 × 10 ⁶ to about 1 × 10 ⁹ cell equivalents of probiotic (s) per 100 kcal nutritional composition. . In certain other embodiments, the amount of probiotic cell equivalents varies from about 1 × 10 ⁷ to about 1 × 10 ⁸ cell equivalents of probiotic (s) per 100 kcal of nutritional composition. obtain.

  In some embodiments, the probiotic source incorporated into the nutritional composition may include both viable colony forming units and non-viable cell equivalents.

  Although probiotics may be useful for pediatric patients, the administration of live bacteria to pediatric subjects, particularly infants, may result in impaired gut defense and immature gut barriers due to the risk of bacteremia. The function may be insufficient. Thus, there is a need for compositions that can provide probiotic benefits without introducing viable bacteria into the intestinal tract of pediatric subjects.

  Without wishing to be bound by theory, it is believed that the culture supernatant from a batch culture of probiotic, in certain embodiments, LGG, provides beneficial gastrointestinal benefits. The beneficial effect on intestinal barrier function is due to a mixture of components (including proteinaceous substances and possibly (exo) polysaccharide substances) that are released into the medium later in the exponential (or “log”) phase of LGG batch culture. Hereinafter, this composition is referred to as “culture supernatant”.

  Thus, in some embodiments, the nutritional composition comprises a culture supernatant from the late exponential growth phase of the probiotic batch culture process. Without wishing to be bound by theory, the activity of the culture supernatant is determined by the components (proteinaceous substances, and possibly () that were released into the medium later in the exponential (or “logarithmic”) phase of the probiotic batch culture. The term “culture supernatant” as used herein includes a mixture of components found in a medium. The steps recognized in batch culture of bacteria are known to those skilled in the art. These are the “induction” phase, the “log” phase (logarithmic phase or “exponential” phase), the “stationary” phase and the “death” phase (or “logarithmic decline” phase). In all phases where viable bacteria are present, the bacteria metabolize nutrients from the medium and also secrete (exact and release) substances into the culture medium. The composition of the secretions at a given time point during the growth phase is generally not predictable.

  In one embodiment, the culture supernatant comprises (a) culturing a probiotic such as LGG in a suitable medium using a batch process; (b) between the delayed phase and the stationary phase of the batch culture process. Collecting the culture supernatant at the late exponential growth phase of the culture step, defined with reference to the latter half of the time; (c) optionally keeping the molecular weight component at 5-6 kilodaltons (kDa) or higher And removing the low molecular weight component from the supernatant; (d) removing the liquid contents from the culture supernatant to obtain a composition.

  The culture supernatant may contain secreted material harvested from the late exponential phase. The late exponential phase occurs after the mid-exponential phase (half time of the exponential phase and thus refers to the late exponential phase, which is the latter half of the time between the induction and stationary phases). In particular, the term “late exponential phase” is used herein to refer to the second quarter of the time between the induction and stationary phases of the LGG batch culture process. In some embodiments, the culture supernatant can be harvested at a time between 75% and 85% of the duration of the exponential phase and can be harvested at about 5/6 of the time elapsed during the exponential phase.

  The culture supernatant is believed to contain a mixture of amino acids, oligos and polypeptides, and proteins of various molecular weights. The composition is further believed to include polysaccharide structures and / or nucleotides.

  In some embodiments, the culture supernatants of the present disclosure exclude low molecular weight components that are generally less than 6 kDa, or even less than 5 kDa. In these and other embodiments, the culture supernatant does not include lactic acid and / or lactate. These low molecular weight components can be removed, for example, by filtration or column chromatography.

  The culture supernatants of the present disclosure can be formulated in various ways for administration to pediatric subjects. For example, the culture supernatant can be used as it is. Or it can be incorporated into a liquid nutritional composition, such as a beverage, or it can be processed before further use. Such treatment generally involves separating the compound from the generally liquid continuous phase of the supernatant. This is preferably done by a drying method such as spray drying or freeze drying (freeze drying). Spray drying is preferred. In a preferred embodiment of the spray drying method, a carrier material, such as maltodextrin DE29, is added prior to spray drying.

The LGG culture supernatant of the present disclosure, even when added via a separate dosage form or nutritional product, is generally effective in promoting intestinal regeneration, promoting intestinal maturation and / or protecting intestinal barrier function. Administered in an amount. An effective amount preferably corresponds to 1 × 10 ⁴ to about 1 × 10 ¹² cell equivalents of live probiotic bacteria per kg body weight per day, more preferably 10 ⁸ to 10 ⁹ cell equivalents per kg body weight per day. . In other embodiments, the amount of cell equivalent may vary from about 1 × 10 ⁴ to about 1.5 × 10 ¹⁰ cell equivalents of probiotic (s) per 100 kcal. In some embodiments, the amount of probiotic cell equivalent can be from about 1 × 10 ⁶ to about 1 × 10 ⁹ cell equivalents of probiotic (s) per 100 kcal of nutritional composition. In certain other embodiments, the amount of probiotic cell equivalents varies from about 1 × 10 ⁷ to about 1 × 10 ⁸ cell equivalents of probiotic (s) per 100 kcal of nutritional composition. obtain.

  Without being bound by any theory, the combination of the disclosed food butyrate and probiotics, especially LGG, may result in normal diet, rapid management of CMA symptoms in allergic infants and children It is likely to promote the acquisition of tolerance in infants affected by CMA. It is believed that the unique nutrient combinations in the disclosed nutritional composition can provide new and unexpected benefits to infants and children. Furthermore, the benefits of this nutritional composition are believed to be gained in infancy and are also believed to be gained by including it as part of a variety of meals as the child continues to grow.

  In one embodiment, the nutritional composition further comprises an ingredient for stimulating endogenous butyric acid production. For example, in some embodiments, the component that stimulates endogenous butyric acid production comprises a microbial stimulating component that is a prebiotic that includes both polydextrose (PDX) and galactooligosaccharide (GOS). Prebiotic components, including PDX and GOS, can promote butyric acid production by microorganisms. Butyrate has epigenetics (histone deacetylase inhibitory activity) that lead to regulatory responses such as the generation of regulatory T cells. In the context of milk allergies, these regulatory responses may accelerate the acquisition of resistance to milk proteins.

  In addition to PDX and GOS, the nutritional composition can also include one or more other prebiotics that can provide additional health benefits, and one or more of the beneficial enteric bacteria. It has a positive impact on the selective stimulation of growth and / or activity of a given number, stimulation of growth and / or activity of ingested probiotic microorganisms, selective reduction of intestinal pathogens, and intestinal short chain fatty acid profiles. Such prebiotics are naturally occurring, synthesized, or biological and / or plant genes, whether such new sources are currently known or later developed Developed by operation. Prebiotics useful in the present disclosure may include oligosaccharides, polysaccharides and other prebiotics including fructose, xylose, soybean, galactose, glucose and mannose.

  That is, prebiotics useful in the present disclosure include PDX and GOS, and in some embodiments, PDX powder, lactoseose, lactosucrose, raffinose, gluco-oligosaccharides, inulin, fructooligosaccharide (FOS), isoforms Maltooligosaccharides, soybean oligosaccharides, lactosucrose, xylo-oligosaccharides (XOS), chitooligosaccharides, manno-oligosaccharides, aribono-oligosaccharides, fuco-oligosaccharides, and gentio-oligosaccharides may be included.

  In one embodiment, the total amount of prebiotic present in the nutritional composition may be from about 1.0 g / L to about 10.0 g / L of the composition. More preferably, the total amount of prebiotic present in the nutritional composition may be from about 2.0 g / L to about 8.0 g / L of the composition. In some embodiments, the total amount of prebiotic present in the nutritional composition may be from about 0.01 g / 100 kcal to about 1.5 g / 100 kcal. In certain embodiments, the total amount of prebiotic present in the nutritional composition may be from about 0.15 g / 100 kcal to about 1.5 g / 100 kcal. In some embodiments, the prebiotic component comprises at least 20% w / w of PDX and GOS.

  In one embodiment, the amount of PDX in the nutritional composition may be in the range of about 0.015 g / 100 kcal to about 1.5 g / 100 kcal. In another embodiment, the amount of polydextrose is in the range of about 0.2 g / 100 kcal to about 0.6 g / 100 kcal. In some embodiments, PDX may be included in the nutritional composition in an amount sufficient to provide between about 1.0 g / L and 10.0 g / L. In another embodiment, the nutritional composition comprises PDX in an amount between about 2.0 g / L and 8.0 g / L. In still other embodiments, the amount of PDX in the nutritional composition may be from about 0.05 g / 100 kcal to about 1.5 g / 100 kcal.

  The prebiotic component also includes GOS. In one embodiment, the amount of GOS in the nutritional composition may be from about 0.015 g / 100 kcal to about 1.0 g / 100 kcal. In another embodiment, the amount of GOS in the nutritional composition may be from about 0.2 g / 100 kcal to about 0.5 g / 100 kcal.

  In certain embodiments, GOS and PDX are supplemented to the nutritional composition in a total amount of at least about 0.015 g / 100 kcal or from about 0.015 g / 100 kcal to about 1.5 g / 100 kcal. In some embodiments, the nutritional composition may comprise GOS and PDX in a total amount of about 0.1 to about 1.0 g / 100 kcal.

  In certain embodiments, PDX and GOS containing prebiotics and food butyrate are incorporated into a nutritional composition that is an infant formula. Currently, many infant formulas do not contain food butyrate. One reason that infant formulas contain little or no food butyrate is due to the unpleasant sensory stimulation properties exhibited by the nutritional composition when the butyric acid compound is incorporated into the nutritional composition. For example, many butyrate compounds exhibit an odor that consumes the nutritional composition and incorporates an unpleasant experience therein. Furthermore, children and infant populations will not readily consume nutritional products that have an unpleasant odor, taste and / or mouthfeel. Accordingly, there is a need for a nutritional composition formulated for administration to a pediatric subject or infant that provides butyrate in the intestine but does not have a diminished sensory stimulation property. Incorporation of prebiotics into the intestinal and infant nutritional compositions to stimulate intestinal microflora and certain dietary butyrate compounds disclosed herein, i.e., butyrate production by glycerol esters of butyric acid, It still provides a pleasant sensory experience.

  In some embodiments, the nutritional composition comprises a protein equivalent source, wherein the protein equivalent source is SEQ ID NO: 4, SEQ ID NO: 13, SEQ ID NO: 17, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 30, SEQ ID NO: 31. , SEQ ID NO: 32, SEQ ID NO: 51, SEQ ID NO: 57, SEQ ID NO: 60, and SEQ ID NO: 63. In some embodiments, the peptide component may include additional peptides disclosed in Table1. For example, the composition may comprise at least 10 additional peptides disclosed in Table1. In some embodiments, 20% -80% of the protein equivalent source comprises a peptide component, and 20% -80% of the protein equivalent source comprises intact protein, partially hydrolyzed protein, and combinations thereof. In some embodiments, the term “addition” means selecting a peptide that is different from those listed.

  In another embodiment, 1% to 99% of the protein equivalent source comprises SEQ ID NO: 4, SEQ ID NO: 13, SEQ ID NO: 17, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, sequence A peptide component comprising at least three peptides selected from the group consisting of SEQ ID NO: 51, SEQ ID NO: 57, SEQ ID NO: 60 and SEQ ID NO: 63, and at least five additional peptides selected from Table 1; % To 99% include intact proteins, partially hydrolyzed proteins, or combinations thereof. In some embodiments, 20% -80% of the protein equivalent source comprises SEQ ID NO: 4, SEQ ID NO: 13, SEQ ID NO: 17, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32 A peptide component comprising at least three peptides selected from the group consisting of SEQ ID NO: 51, SEQ ID NO: 57, SEQ ID NO: 60 and SEQ ID NO: 63, and at least five additional peptides selected from Table 1; 20% to 80% of the protein contains intact proteins, partially hydrolyzed proteins, or combinations thereof.

Table 1 below identifies the amino acid sequence of a peptide that can be included in the peptide component of the nutritional composition.

Table 2 below further identifies a subset of Table 1's amino acid sequence that may be included in the peptide components disclosed herein.

  In some embodiments, the peptide component may be present in the nutritional composition in an amount from about 0.2 g / 100 kcal to about 5.6 g / 100 kcal. In other embodiments, the peptide component may be present in the nutritional composition in an amount from about 1 g / 100 kcal to about 4 g / 100 kcal. In yet other embodiments, the peptide component may be present in the nutritional composition in an amount from about 2 g / 100 kcal to about 3 g / 100 kcal.

  The peptide components disclosed herein can be formulated with other components in a nutritional composition to provide the appropriate nutritional level for the target subject. In some embodiments, the peptide component is included in a nutritionally complete formulation suitable to support normal growth.

  The peptide component can be provided as an element of a protein equivalent source. In some embodiments, the peptides identified in Table 1 and Table 2 can be provided by protein equivalent sources derived from milk protein, including but not limited to bovine casein and bovine whey. In some embodiments, the protein equivalent source comprises hydrolyzed bovine casein or hydrolyzed bovine whey. Thus, in some embodiments, the peptides identified in Table 1 and Table 2 can be provided by casein hydrolysates. Such peptides can be obtained by hydrolysis or synthesized in vitro by methods known to those skilled in the art.

  Non-limiting examples of hydrolysis methods are disclosed herein. In some embodiments, this method can be used to obtain protein hydrolysates and peptides of the present disclosure. Protein is hydrolyzed using protease N, protease N. Protease N “Amano” is manufactured by Amano Enzyme US S. A. Co. , Ltd., Ltd. , Elgin, IL. Protease N is a proteolytic enzyme preparation derived from a bacterial species of Bacillus subtilis. Protease powder is identified as “150,000 units / g or more”, meaning that one unit of protease N is the amount of enzyme that produces an amino acid equivalent to 100 micrograms of tyrosine at pH 7.0 for 60 minutes. . Protease N can be used at a level of about 0.5% to about 1.0% by weight of the total protein to be hydrolyzed to produce the infant formula of the present disclosure.

  Proteolysis with protease N is typically performed at a temperature of about 50 ° C. The hydrolysis is performed for a certain time to obtain a degree of hydrolysis of about 4% to 10%. In certain embodiments, the hydrolysis occurs over a period of time to obtain a degree of hydrolysis of about 6% to 9%. In another embodiment, hydrolysis occurs for a period of time to obtain a degree of hydrolysis of about 7.5%. This level of hydrolysis can take from about 30 minutes to about 3 hours.

  A constant pH should be maintained during the hydrolysis. In the disclosed method, the pH is adjusted and maintained at about 6.5-8. In certain embodiments, the pH is maintained at about 7.0.

  In order to maintain an optimum pH of the whey protein, casein, water and protease N solution, a sodium hydroxide and / or potassium hydroxide caustic solution can be used to adjust the pH during hydrolysis. When adjusting the pH with sodium hydroxide, the amount of sodium hydroxide added to the solution should be controlled to a level comprising less than about 0.3% of the total solids in the final protein hydrolysate. . In order to maintain the optimum pH, a 10% potassium hydroxide solution can also be used to adjust the pH of the solution to the desired value before adding the enzyme or during the hydrolysis process.

  The amount of caustic solution added to the solution during protein hydrolysis can be controlled by pH-stat or by adding caustic solution continuously and proportionally. The hydrolyzate can be produced by standard batch or continuous processes.

  In order to ensure a more consistent quality of the partial protein hydrolyzate, the hydrolyzate is enzyme-inactivated to terminate the hydrolysis process. The enzyme deactivation step can be performed by a heat treatment at a temperature of about 82 ° C. for about 10 minutes. Alternatively, the enzyme can be inactivated by heating the solution to a temperature of about 92 ° C. for about 5 seconds. After enzyme deactivation is complete, the hydrolyzate can be stored in a liquid state at temperatures below 10 ° C.

  In some embodiments, the protein equivalent source comprises a hydrolyzed protein including partially hydrolyzed proteins such as casein and extensively hydrolyzed proteins. In some embodiments, the protein equivalent source comprises a hydrolyzed protein comprising a peptide having a molar mass distribution greater than 500 Daltons. In some embodiments, the hydrolyzed protein comprises a peptide having a molar mass distribution ranging from about 500 daltons to about 1,500 daltons. Further, in some embodiments, the hydrolyzed protein may comprise a peptide having a molar mass distribution range of about 500 Daltons to about 2,000 Daltons.

  In some embodiments, the protein equivalent source may include peptide components, intact proteins, partially hydrolyzed proteins and / or hydrolyzed proteins including extensively hydrolyzed proteins, and combinations thereof. In some embodiments, 20% to 80% of the protein equivalent source comprises a peptide component disclosed herein. In some embodiments, 30% to 60% of the protein equivalent source comprises a peptide component disclosed herein. In yet other embodiments, 40-50% of the protein equivalent source comprises a peptide component.

  In some embodiments, 20% -80% of the protein equivalent source comprises intact protein, partially hydrolyzed protein, extensively hydrolyzed protein, or combinations thereof. In some embodiments, 40% to 70% of the protein equivalent source comprises intact protein, partially hydrolyzed protein, extensively hydrolyzed protein, or combinations thereof. In further embodiments, 50% to 60% of the protein equivalent source may comprise intact protein, partially hydrolyzed protein, extensively hydrolyzed protein, or combinations thereof.

  In some embodiments, the protein equivalent source comprises a partially hydrolyzed protein having a degree of hydrolysis of less than 40%. In yet other embodiments, the protein equivalent source may comprise a partially hydrolyzed protein having a degree of hydrolysis of less than 25%, or less than 15%.

  In some embodiments, the nutritional composition comprises about 1 g to about 7 g of protein source per 100 kcal. In other embodiments, the nutritional composition comprises from about 3.5 g to about 4.5 g protein per 100 kcal.

  Without being bound by any particular theory, administration of the nutritional compositions disclosed herein can reduce allergic reactions and improve tolerance to milk allergy in certain subjects. In some embodiments, a combination of a probiotic such as LGG, a food butyrate and a protein equivalent source provides a synergistic health benefit.

  The nutritional composition of the present disclosure may also include a carbohydrate source. The carbohydrate source can be any used in the art, such as lactose, glucose, fructose, corn syrup solids, maltodextrin, sucrose, starch, rice syrup solids, and the like. The amount of carbohydrate in the nutritional composition typically can vary between about 5 g to about 25 g / 100 kcal. In some embodiments, the amount of carbohydrate is from about 6 g to about 22 g / 100 kcal. In other embodiments, the amount of carbohydrate is from about 12 g to about 14 g / 100 kcal. In some embodiments, corn syrup solids are preferred. In addition, hydrolyzed, partially hydrolyzed and / or extensively hydrolyzed carbohydrates may be desirable to include in the nutritional composition due to their easy digestibility. Specifically, hydrolyzed carbohydrates are unlikely to contain allergenic epitopes.

  Non-limiting examples of carbohydrate materials suitable for use herein include hydrolyzed or intact, natural or chemically modified, waxy or non-derived from corn, tapioca, rice or potato A waxy starch is mentioned. Non-limiting examples of suitable carbohydrates include hydrolyzed corn starch, maltodextrin, maltose, corn syrup, dextrose, corn syrup solids, various hydrolyzed starches characterized as glucose, and various other glucoses Examples include polymers, as well as combinations thereof. Non-limiting examples of other suitable carbohydrates include those often referred to as indigestible oligosaccharides such as sucrose, lactose, fructose, high fructose corn syrup, fructooligosaccharides, and combinations thereof.

  The nutritional composition of the present disclosure may also include a protein source. The protein source may be any of those used in the art, such as skim milk, whey protein, casein, soy protein, hydrolyzed protein, amino acid, and the like. Milk protein sources useful in the practice of the present disclosure include, but are not limited to, milk protein powder, milk protein concentrate, milk protein isolate, skim milk solid, skim milk, skim milk powder, whey protein, whey protein isolate, Examples include whey protein concentrate, sweet whey, acid whey, casein, acid casein, casein salts (eg, sodium caseinate, sodium caseinate calcium, casein calcium), and any combination thereof.

  In one embodiment, the protein of the nutritional composition is provided as an intact protein. In other embodiments, the protein is provided as a combination of both intact and partially hydrolyzed proteins and has a degree of hydrolysis of about 4% to 10%. In certain other embodiments, the protein is more fully hydrolyzed. In yet other embodiments, the protein source includes amino acids. In yet another embodiment, the protein source can be supplemented with a glutamine-containing peptide.

  In certain embodiments of the nutritional composition, the whey: casein ratio of the protein source is similar to that found in human breast milk. In one embodiment, the protein source comprises about 40% to about 80% whey protein and about 20% to about 60% casein.

  In some embodiments, the nutritional composition comprises about 1 g to about 7 g of protein source per 100 kcal. In other embodiments, the nutritional composition comprises from about 3.5 g to about 4.5 g protein per 100 kcal.

  In some embodiments, the nutritional compositions described herein include a fat source. The rich lipid fraction described herein may be the sole fat source or may be used in combination with other suitable fat or lipid sources for nutritional compositions known in the art. Good. In certain embodiments, suitable fat sources include animal sources such as milk fat, butter, butter fat, egg yolk lipid; marine sources such as fish oil, marine oil, single cell oil; corn oil, sunflower oil, soybean oil, palm Vegetable oils such as olein oil, palm oil, high oleic sunflower oil, evening primrose oil, rapeseed oil, olive oil, linseed oil, cottonseed oil, high oleic safflower oil, palm stearin, palm kernel oil, wheat germ oil; medium chain triglyceride oil and emulsion And fatty acid esters; and any combination thereof.

  In some embodiments, the nutritional composition comprises from about 1 g / 100 kcal to about 10 g / 100 kcal fat or lipid source. In some embodiments, the nutritional composition comprises about 2 g / 100 kcal to about 7 g / 100 kcal of fat source. In other embodiments, the fat source may be present in an amount from about 2.5 g / 100 kcal to about 6 g / 100 kcal. In yet other embodiments, the fat source may be present in the nutritional composition in an amount from about 3 g / 100 kcal to about 4 g / 100 kcal.

  In some embodiments, the fat or lipid source comprises about 10% to about 35% coconut oil per total amount of fat or lipid. In some embodiments, the fat or lipid source comprises about 15% to about 30% coconut oil per total amount of fat or lipid. In still other embodiments, the fat or lipid source may comprise about 18% to about 25% palm oil per total amount of fat or lipid.

  In certain embodiments, the fat or lipid source may be formulated to include about 2% to about 16% soybean oil, based on the total amount of fat or lipid. In some embodiments, the fat or lipid source may be formulated to include about 4% to about 12% soybean oil, based on the total amount of fat or lipid. In some embodiments, the fat or lipid source may be formulated to include about 6% to about 10% soybean oil, based on the total amount of fat or lipid.

  In certain embodiments, the fat or lipid source may be formulated to include about 2% to about 16% coconut oil based on the total amount of fat or lipid. In some embodiments, the fat or lipid source may be formulated to include about 4% to about 12% coconut oil based on the total amount of fat or lipid. In some embodiments, the fat or lipid source may be formulated to include about 6% to about 10% coconut oil, based on the total amount of fat or lipid.

  In certain embodiments, the fat or lipid source may be formulated to include about 2% to about 16% sunflower oil, based on the total amount of fat or lipid. In some embodiments, the fat or lipid source may be formulated to include about 4% to about 12% sunflower oil based on the total amount of fat or lipid. In some embodiments, the fat or lipid source may be formulated to include about 6% to about 10% sunflower oil, based on the total amount of fat or lipid.

  In some embodiments, the oils, i.e. sunflower oil, soybean oil, sunflower oil, palm oil, etc. are directed to fortified versions of such oils known in the art. For example, in certain embodiments, the use of sunflower oil may include high oleic sunflower oil. In other examples, the use of such oils can be enriched with certain fatty acids, as is known in the art, and can be used with the fat or lipid sources disclosed herein. .

  In some embodiments, the nutritional composition may also include a source of long chain polyunsaturated fatty acids (LCPUFA). In one embodiment, the amount of LCPUFA in the nutritional composition is at least about 5 mg / 100 kcal and may vary from about 5 mg / 100 kcal to about 100 mg / 100 kcal, more preferably from about 10 mg / 100 kcal to about 50 mg / 100 kcal. Non-limiting examples of LCPUFA include docosahexaenoic acid (DHA), arachidonic acid (ARA), linoleic acid (18: 2n-6), γ-linolenic acid (18: 3n-6), dihomo of the n-6 pathway. -Γ-linolenic acid (20: 3n-6), α-linolenic acid (18: 3n-3), stearidone (18: 4n-3), eicosatetraenoic acid (20: 4n-3), eicosapentaenoic acid (20: 5n-3) and docosapentaenoic acid (22: 6n-3), but are not limited to these.

  In some embodiments, the LCPUFA included in the nutritional composition may include DHA. In one embodiment, the amount of DHA in the nutritional composition is at least about 17 mg / 100 kcal and may vary from about 5 mg / 100 kcal to about 75 mg / 100 kcal, more preferably from about 10 mg / 100 kcal to about 50 mg / 100 kcal.

  In another embodiment, the nutritional composition is supplemented with both DHA and ARA, particularly when the nutritional composition is an infant formula. In this embodiment, the weight ratio of ARA: DHA may be about 1: 3 to about 9: 1. In certain embodiments, the ratio of ARA: DHA is about 1: 2 to about 4: 1.

  DHA and ARA can be in natural form as long as the remainder of the LCPUFA source does not have a substantially detrimental effect on the infant. Alternatively, DHA and ARA can be used in purified form.

  The disclosed nutritional compositions described herein may include a β-glucan source in some embodiments. Glucans are polysaccharides, specifically glucose polymers, that exist in nature and can be found in the cell walls of bacteria, yeast, fungi and plants. Beta glucan (β-glucan) itself is a diverse subset of glucose polymers that are composed of chains of glucose monomers that are joined together through beta-type glycosidic bonds to form complex carbohydrates.

  β-1,3-glucan is a carbohydrate polymer purified from, for example, yeast, mushrooms, bacteria, algae or cereals. (Stone BA, Clark AE. Chemistry and Biology of (1-3) -Beta-Glucans. London: Portland Press Ltd; 1993.) The chemical structure of β-1,3-glucan is that of β-1,3-glucan. Depends on the source. In addition, various physiochemical parameters such as solubility, primary structure, molecular weight and branching play a role in the biological activity of β-1,3-glucan. (Yadomae T., Structure and biologics of fungal beta-1, 3-glucans. Yakugaku Zashishi. 2000; 120: 413-431.)

  β-1,3-glucans are natural polysaccharides with or without β-1,6-glucose side chains found in the cell walls of various plants, yeasts, fungi, and bacteria. β-1,3; 1,6-glucan contains glucose units with (1,3) linkages having side chains attached at the (1,6) position (several cases). The β-1,3; 1,6-glucan has a common structure including a skeleton of linear glucose units linked by β-1,3 bonds with a β-1,6-linked glucose branched chain extending from this skeleton. A heterogeneous group of glucose polymers that share sex. This is the basic structure for the currently described class of β-glucans, but there can be several variations. For example, certain yeast β-glucans have additional regions of β (1,3) branches extending from β (1,6) branches, adding additional complexity to their respective structures.

  Β-glucan derived from Saccharomyces cerevisiae, which is a baker's yeast, is a chain of D-glucose molecules connected at the 1st and 3rd positions with the side chain of glucose attached at the 1st and 6th positions. Composed. Yeast-derived β-glucan generally has a linear general structure of glucose units having a β-1,3 skeleton in which β-1,6 side chains of 6 to 8 glucose units in length are interspersed. It is an insoluble, fiber-like complex sugar. More specifically, β-glucan derived from baker's yeast is poly (1,6) -β-D-glucopyranosyl- (1,3) -β-D-glucopyranose.

  Furthermore, β-glucan is well tolerated and does not cause or cause excessive gas, abdominal distension, swelling, or diarrhea in pediatric subjects. The addition of β-glucan to nutritional compositions for pediatric subjects such as infant formulas, glowing-up milks, or other pediatric nutritional products improves the immune response of the subject by increasing resistance to pathogen invasion. Therefore, maintain or improve overall health.

  In some embodiments, the β-glucan is β-1,3; 1,6-glucan. In some embodiments, the β-1,3; 1,6-glucan is derived from baker's yeast. The nutritional composition comprises whole glucan particles β-glucan, granular β-glucan, PGG-glucan (poly-1,6-β-D-glucopyranosyl-1,3-β-D-glucopyranose) or any mixture thereof May be included.

  In some embodiments, the amount of β-glucan in the nutritional composition is about 3 mg to about 17 mg per 100 kcal. In another embodiment, the amount of β-glucan is from about 6 mg to about 17 mg per 100 kcal.

  The disclosed nutritional compositions described herein may include an effective amount of iron in some embodiments. Iron can be in the form of encapsulated iron, such as encapsulated ferrous fumarate or encapsulated ferrous sulfate, or reactive such as ferric pyrophosphate or ferric orthophosphate. Low iron form may be included.

  One or more vitamins and / or minerals may also be added to the nutritional composition in an amount sufficient to provide the subject's daily nutritional requirements. It should be understood by those skilled in the art that vitamin and mineral requirements vary, for example, based on the age of the child. For example, an infant may have different vitamin and mineral requirements than a 1 to 13 year old child. Thus, the embodiments are not intended to limit the nutritional composition to a particular age group, but rather to provide a range of acceptable vitamin and mineral components.

In embodiments providing a nutritional composition for children, the composition may optionally include, but is not limited to, one or more of the following vitamins or derivatives thereof: vitamin B ₁ (thiamine, thiamine pyrophosphate, TPP, Thiamine triphosphate, TTP, thiamine nitrate, thiamine nitrate), vitamin B ₂ (riboflavin, flavin mononucleotide, FMN, flavin adenine dinucleotide, FAD, lactoflavin, ovoflavin), vitamin B ₃ (niacin, nicotinic acid, nicotinic acid) amide, niacinamide, nicotinamide adenine dinucleotide, NAD, nicotinic acid mononucleotide, NicMN, pyridine-3-carboxylic acid), vitamin B ₃ - precursors tryptophan, vitamin B ₆ (pyridoxine, pyridoxal, pyridoxa Emissions, pyridoxine hydrochloride), pantothenic acid (pantothenate, panthenol), folate (folic acid, folacin, pteroylglutamic acid), vitamin B ₁₂ (cobalamin, methylcobalamin, deoxyadenosyl cobalamin, cyanocobalamin, hydroxy cobalamin, adenosyl cobalamin ), Biotin, vitamin C (ascorbic acid), vitamin A (retinol, retinyl acetate, retinyl palmitate, retinyl ester with other long chain fatty acids, retinal, retinoic acid, retinol ester), vitamin D (calciferol) , cholecalciferol, vitamin D _3, 1,25, - dihydroxyvitamin D), vitamin E (alpha-tocopherol, alpha-tocopherol acetate, alpha-tocopherol succinate, alpha-nicotinate Tokofe Lumpur, alpha-tocopherol), vitamin K (vitamin K _1, phylloquinone, naphthoquinone, vitamin K _2, menaquinone-7, vitamin K _3, menaquinone -4, menadione, menaquinone -8, menaquinone-8H, menaquinone-9, menaquinone -9H, menaquinone-10, menaquinone-11, menaquinone-12, menaquinone-13), choline, inositol, β-carotene, and any combination thereof.

  In embodiments that provide a pediatric nutritional composition, such as glowing-up milk, the nutritional composition may optionally include, but is not limited to, one or more of the following minerals or derivatives thereof: boron, calcium, calcium acetate, Calcium gluconate, calcium chloride, calcium lactate, calcium phosphate, calcium sulfate, chloride, chromium, chromium chloride, chromium picolinate, copper, copper sulfate, copper gluconate, cupric sulfate, fluoride, Iron, carbonyl iron, ferric iron, ferrous fumarate, ferric orthophosphate, iron powder, polysaccharide iron, iodide, iodine, magnesium, magnesium carbonate, magnesium hydroxide, Oxidation Gnesium, magnesium stearate, magnesium sulfate, manganese, molybdenum, phosphorus, potassium, potassium phosphate, potassium iodide, potassium chloride, potassium acetate, selenium, sulfur, sodium, doxate sodium, sodium chloride, sodium selenate, molybdic acid Sodium, zinc, zinc oxide, zinc sulfate, and mixtures thereof. Non-limiting exemplary derivatives of mineral compounds include salts, alkali salts, esters, and chelates of any mineral compound.

  Growing up milk or other pediatric nutritional compositions include calcium phosphate, calcium glycerol phosphate, sodium citrate, potassium chloride, potassium phosphate, magnesium phosphate, ferrous sulfate, zinc sulfate, copper sulfate, manganese sulfate, and Minerals may be added in the form of a salt such as sodium selenite. Additional vitamins and minerals may be added as is known in the art.

  The nutritional composition of the present disclosure optionally includes the following flavors, such as flavored extracts, volatile oils, cocoa or chocolate flavors, peanut butter flavors, cookie crumbs, vanilla, or any commercially available flavor. One or more fragrances may be included. Examples of useful flavors include, but are not limited to, pure anise extract, substitute banana extract, substitute cherry extract, chocolate extract, pure lemon extract, pure orange extract, pure peppermint extract, honey, substitute pineapple extract , Ram extract, strawberry extract, or vanilla extract; or volatile oil such as balm oil, bay oil, bergamot oil, cedarwood oil, cherry oil, cinnamon oil, clove oil, or peppermint oil; peanut butter , Chocolate flavors, vanilla cookie crumbs, butterscotch, toffee, and mixtures thereof. The amount of fragrance may vary greatly depending on the fragrance used. As is known in the art, the type and amount of flavor can be selected.

  The nutritional composition of the present disclosure may optionally include one or more emulsifiers that may be added for the stability of the final product. Examples of suitable emulsifiers include, but are not limited to, lecithin (eg, derived from eggs or soybeans), alpha-lactalbumin, and / or mono- and di-glycerides, and mixtures thereof. Other emulsifiers will be readily apparent to those skilled in the art, and the selection of suitable emulsifier (s) will depend, in part, on the formulation and the final product.

  The nutritional composition of the present disclosure may also optionally include one or more preservatives to extend the shelf life of the product. Suitable preservatives include, but are not limited to, potassium sorbate, sodium sorbate, potassium benzoate, sodium benzoate, disodium calcium EDTA, and mixtures thereof.

  The nutritional composition of the present disclosure may optionally include one or more stabilizers. Suitable stabilizers for use in the practice of the nutritional compositions of the present disclosure include, but are not limited to, gum arabic, gum ghatti, karaya gum, gum tragacanth, agar, far celeran, guar gum, gellan gum, locust bean gum, pectin, low Methoxyl pectin, gelatin, microcrystalline cellulose, CMC (sodium carboxymethylcellulose), methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, DATEM (diacetyl tartaric acid esters of mono- and diglycerides), dextran, carrageenan, and mixtures thereof Can be mentioned.

  The nutritional compositions of the present disclosure may provide minimal nutrition, partial nutrition, or total nutrition. The composition may be a nutritional supplement or a meal substitute. The composition may be nutritionally complete, but not necessarily. In one embodiment, the nutritional composition of the present disclosure is nutritionally complete and comprises suitable types and amounts of lipids, carbohydrates, proteins, vitamins and minerals. The amount of lipid or fat can typically vary from about 1 g / 100 kcal to about 25 g / 100 kcal. The amount of protein typically can vary from about 1 g / 100 kcal to about 7 g / 100 kcal. The amount of carbohydrate typically can vary from about 6 g / 100 kcal to about 22 g / 100 kcal.

  In one embodiment, the pediatric nutritional composition comprises a maximum dietary recommendation for any given country per serving of vitamin A, vitamin C and vitamin E, zinc, iron, iodine, selenium and choline. About 10% to about 50%, or about 10% to about 50% of the average dietary recommendation of a group of countries. In another embodiment, the pediatric nutritional composition is about 10% to 30% of the maximum dietary recommendation of any given country per serving of vitamin B, or about the average dietary recommendation of a group of countries. 10% to 30% may be supplied. In yet another embodiment, the levels of vitamin D, calcium, magnesium, phosphorus and potassium in pediatric nutritional products may correspond to reference values found in milk. In other embodiments, the other nutrients in the pediatric nutritional composition are about 20% of the maximum dietary recommendation for any given country per serving, or about 20 of the average dietary recommendation for a group of countries. % May be present.

  In some embodiments, the nutritional composition is an infant formula. Infant formulas are fortified nutritional compositions for infants. Infant formula content is determined by federal regulations that define macronutrients, vitamins, minerals and other ingredient levels to simulate the nutrition and other properties of breast milk. Infant formulas generally promote health and development in pediatric subjects such as infants and children.

  In some embodiments, the nutritional composition of the present disclosure is a growing up milk. Growing up milk is an enhanced milk-based beverage intended for children over 1 year old (typically 1 to 3 years old, 4 to 6 years old, or 1 to 6 years old). Growing-up milk is not a special diet for the sick and is not intended as a meal replacement or supplement to address specific nutritional deficiencies. Instead, Growing Up Milk achieves a continuous and daily intake of additional functional dietary ingredients such as all essential vitamins and minerals, macronutrients and non-essential nutrients intended for health promoting properties in children. Designed with the intention to serve as a supplement to a variety of diets to provide additional insurance.

  The exact composition of the growing-up milk or other nutritional composition according to the present disclosure may vary from market to market depending on local regulations and target group dietary intake information. In some embodiments, a nutritional composition according to the present disclosure consists of a milk protein source, such as whole milk or skim milk, sugars and sweeteners added to achieve the desired sensory properties, and additional vitamins and minerals. . The fat composition includes a concentrated lipid fraction derived from milk. Total protein can be targeted to match human milk, total milk protein, or lower values. Total carbohydrates are usually targeted to be provided as additional sugars, such as sucrose or fructose, as small as possible to achieve an acceptable taste. Typically, vitamin A, calcium and vitamin D are added at a level consistent with the nutritional contribution of local milk. Alternatively, in some embodiments, vitamins and minerals may be added at a level that provides approximately 20% dietary reference intake (DRI) or 20% daily value (DV) per serving. Also good. Furthermore, nutritional values can vary between markets depending on the intended nutritional requirements of the intended population, ingredient contributions and local regulations.

  The disclosed nutritional composition (s) are available in the art such as powders, gels, suspensions, pastes, solids, liquids, liquid concentrates, reconstitutable milk powder substitutes or ready-to-use products. It may be provided in any form known in the art. The nutritional composition, in certain embodiments, is a nutritional supplement, pediatric nutrition product, infant formula, human milk fortifier, glowing up milk, or any other nutritional composition designed for infant or pediatric subjects. including. The nutritional compositions of the present disclosure include health promoting substances, for example for oral consumption, including, for example, foods, beverages, tablets, capsules, and powders. Further, the nutritional composition of the present disclosure may be standardized to a specific caloric content, and the composition may be provided as a ready-to-use product or may be provided in a concentrated form. In some embodiments, the nutritional composition is in the form of a powder having a particle size in the range of 5 μm to 1500 μm, more preferably in the range of 10 μm to 300 μm.

  The nutritional composition of the present disclosure may be provided in a suitable container system. For example, non-limiting examples of suitable container systems include plastic containers, metal containers, foil pouches, plastic pouches, multilayer pouches, and combinations thereof. In certain embodiments, the nutritional composition may be a powder composition contained within a plastic container. In certain other embodiments, the nutritional composition may be contained in a plastic pouch located inside the plastic container.

  In some embodiments, the nutritional compositions described herein advantageously reduce the incidence of allergic reactions in a subject and improve resistance to milk allergies. Further, in some embodiments, the nutritional composition advantageously reduces the inflammatory response caused by allergies in the subject. Accordingly, the present disclosure relates to a method for improving resistance to milk allergy in a subject. Further, the present disclosure provides for dietary management of allergic diseases and / or allergic reactions in a subject through administration of a nutritional composition comprising a probiotic such as LGG and a food butyrate disclosed herein. Regarding the method.

  In some embodiments, the method includes the steps of taking milk to the target subject and then providing the target subject with the nutritional composition disclosed herein comprising probiotic and food butyrate. In certain embodiments, after feeding the target subject with milk, the target subject may be provided with a nutritional composition comprising probiotics and food butyrate and the protein equivalent source disclosed herein. In certain embodiments, the target subject may be administered a nutritional composition comprising probiotic and food butyrate and a protein equivalent source after exposure to milk or other allergen. In certain embodiments, the protein equivalent source may be substantially free of intact and / or intact proteins. In certain other embodiments, protein equivalent sources may include hydrolyzed proteins, amino acids, peptide components disclosed herein, and combinations thereof. In some embodiments, the nutritional composition includes a protein equivalent source that includes amino acids and does not include hydrolyzed protein or complete / intact protein.

  In some embodiments, the target subject is not provided with milk or allergen prior to administration of the nutritional composition. Thus, in some embodiments, the method provides a nutritional composition disclosed herein comprising food butyrate to a target subject, followed by exposing the target subject to milk or other allergen. The aim is to reduce allergic responses in target subjects.

  In some embodiments, the nutritional compositions described herein advantageously reduce the inflammatory response in the subject. Accordingly, the present disclosure provides a method of reducing a pro-inflammatory response in a subject by administering to the subject a nutritional composition containing a protein equivalent source described herein in combination with a probiotic and a food butyrate About. For example, the method can reduce the production of pro-inflammatory cytokines in the subject.

  In some embodiments, a method of reducing an inflammatory response in a subject comprises administering to the subject a nutritional composition comprising a carbohydrate source, a protein equivalent source, a fat source, PDX / GOS and food butyrate, wherein the protein equivalent The sources are SEQ ID NO: 4, SEQ ID NO: 13, SEQ ID NO: 17, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 51, SEQ ID NO: 57, SEQ ID NO: 60, and SEQ ID NO: 63. Containing peptide components. In some embodiments, the peptide component may include additional peptides disclosed in Table1. For example, the composition may comprise at least 10 additional peptides disclosed in Table1. In some embodiments, 20% -80% of the protein equivalent source comprises a peptide component and 20% -80% of the protein equivalent source comprises intact protein, partially hydrolyzed protein, and combinations thereof.

  In another embodiment, the method comprises administering to the subject a nutritional composition, wherein 20% -80% of the protein equivalent source is SEQ ID NO: 4, SEQ ID NO: 13, SEQ ID NO: 17, sequence Peptide component comprising at least three peptides selected from the group comprising SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 51, SEQ ID NO: 57, SEQ ID NO: 60, and SEQ ID NO: 63 And at least 5 additional peptides selected from Table 1, wherein 20% to 80% of the protein equivalent source comprises intact proteins, partially hydrolyzed proteins, or combinations thereof.

  In yet another embodiment, a method of reducing an inflammatory response includes providing a nutritional composition comprising a peptide component derived from casein hydrolyzate having a molar mass distribution greater than 500 Daltons. In some embodiments, the molar mass distribution of casein hydrolyzate ranges from 500 to 2000 daltons. In other embodiments, a method of reducing an inflammatory response includes providing a nutritional composition comprising a peptide component derived from a casein hydrolyzate that does not comprise a peptide having a molar mass distribution of less than 200 Daltons.

  In some embodiments, the target subject may be a pediatric subject. Further, in one embodiment, the nutritional composition provided to the pediatric subject may be an infant formula. The peptide components, probiotics disclosed herein, and the food butyrate disclosed herein may be added to an infant formula, and each may be selected from a particular source, The concentration may then be adjusted to maximize health benefits. In another embodiment of this method, the nutritional composition comprising the peptide component, probiotic and food butyrate disclosed herein is a growing up milk.

  In embodiments where the nutritional composition is an infant formula, the composition can advantageously reduce the infant's pro-inflammatory response, thereby reducing the occurrence of inflammatory diseases. In addition, the reduction of inflammatory diseases can continue from childhood to adulthood. Similarly, if the nutritional composition is a growing up milk, a child who has taken the growing up milk may experience a reduced incidence of inflammatory diseases in adulthood and childhood.

  In certain embodiments, the present disclosure improves butyrate absorption in a target subject by providing or administering to the target subject a nutritional composition disclosed herein comprising a probiotic and a food butyrate. Regarding the method. In some embodiments, the target subject is a pediatric subject or an infant. In some embodiments, the nutritional composition is an infant formula or growing-up milk.

  All combinations of methods or process steps used herein may be performed in any order, unless otherwise indicated, or unless the context clearly indicates the opposite, depending on the context in which the combination is referenced. it can.

  The methods of the present disclosure, and compositions comprising components thereof, of the embodiments described herein as well as any additional or optional ingredients described herein or useful in nutritional compositions. It may include, consist of, or consist essentially of essential elements and limitations.

  Examples of formulations are provided to illustrate some embodiments of the nutritional composition of the present disclosure, but should not be construed as limiting thereon. Other embodiments within the scope of the claims herein will be apparent to those skilled in the art from consideration of the specification or practice of the nutritional composition or method disclosed herein. This specification, along with examples, is considered to be exemplary only, and the scope and spirit of the disclosure is intended to be indicated by the claims that follow the examples.

Example 2
Table3 provides an exemplary embodiment of a peptide component comprising the eight peptides of Table1.

Table4 provides an exemplary embodiment of a peptide component comprising a specific peptide from Table1.

Table 5, shown below, provides an exemplary embodiment of the nutritional profile of a nutritional composition comprising PDX / GOS and food butyrate and describes the amount of each ingredient included per 100 kcal supply of the nutritional composition .

  All references cited herein include all articles, publications, patents, patent applications, presentations, texts, reports, manuscripts, brochures, books, Internet publications, journal articles, periodicals, etc. , All of which are incorporated herein. The discussion of a reference herein is intended only to summarize the assertions made by its authors, and no reference is admitted to constitute prior art. Applicant reserves the right to challenge the accuracy and validity of the cited documents.

  Although embodiments of the present disclosure have been described using specific terms, devices, and methods, such descriptions are for illustrative purposes only. The language used is a descriptive word, not a limitation. It should be understood that changes and modifications may be made by those skilled in the art without departing from the spirit or scope of the present disclosure as set forth in the appended claims. Further, it should be understood that aspects of the various embodiments may be interchanged in whole or in part. Accordingly, the spirit and scope of the appended claims should not be limited to the description of the versions contained therein.

Claims (20)

A nutritional composition comprising:
Carbohydrate sources;
Protein equivalent source;
Fat or lipid source;
Lactobacillus rhamnosus GG; and (i) food butyrate;
(Ii) an ingredient for stimulating endogenous butyrate; or (iii) a nutritional composition comprising at least one of a combination thereof.   1% to 99% of protein equivalent sources are SEQ ID NO: 4, SEQ ID NO: 13, SEQ ID NO: 17, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 51, SEQ ID NO: 57 , SEQ ID NO: 60, and peptide components comprising SEQ ID NO: 63, wherein 1% to 99% of the protein equivalent source comprises partially hydrolyzed protein, extensively hydrolyzed protein, or combinations thereof The nutritional composition according to claim 1.   2. The peptide component of claim 1, further comprising at least 10 additional peptides selected from Table 1, wherein the peptide component is present in an amount of about 0.2 g / 100 kcal to about 5.6 g / 100 kcal. Nutritional composition.   The nutritional composition of claim 1, wherein the nutritional composition comprises a component for stimulating endogenous butyrate production, and wherein the ingredient for stimulating endogenous butyrate production comprises polydextrose and galactooligosaccharides.   The nutritional composition of claim 1, wherein the nutritional composition comprises food butyrate, and the food butyrate is present in an amount of about 22 mg / 100 kcal to about 280 mg / 100 kcal.   The nutritional composition according to claim 1, wherein the food butyrate comprises sodium butyrate.   The nutritional composition of claim 1, wherein the nutritional composition comprises dietary butyrate provided by a milk-derived concentrated lipid fraction.   The nutritional composition according to claim 7, wherein the milk-derived concentrated lipid fraction further comprises a milk fat globule membrane.   The nutritional composition of claim 1 further comprising one or more long chain polyunsaturated fatty acids.   The nutritional composition of claim 9, wherein the one or more long chain polyunsaturated fatty acids comprises docosahexaenoic acid, arachidonic acid, and combinations thereof.   The nutritional composition according to claim 1, further comprising a prebiotic comprising β-glucan.   The nutritional composition according to claim 1, further comprising a culture supernatant derived from the late exponential growth phase of the probiotic batch culture process.   The nutritional composition of claim 1, wherein the nutritional composition is an infant formula. Per 100 kcal:
(I) from about 6 g to about 22 g of carbohydrate source;
(Ii) about 1 g to about 7 g of protein source;
(Iii) about 1 g to about 10.3 g of fat source;
(Iv) a nutritional composition comprising about 1 × 10 ⁴ CFU to about 1.5 × 10 ¹² CFU of Lactobacillus rhamnosus GG; and (v) about 22 mg to 280 mg of food butyrate.   1% to 99% of protein equivalent sources are SEQ ID NO: 4, SEQ ID NO: 13, SEQ ID NO: 17, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 51, SEQ ID NO: 57 , SEQ ID NO: 60, and peptide components comprising SEQ ID NO: 63, wherein 1% to 99% of the protein equivalent source comprises partially hydrolyzed protein, extensively hydrolyzed protein, or combinations thereof The nutritional composition according to claim 14.   15. The nutritional composition of claim 14, further comprising one or more long chain polyunsaturated fatty acids.   15. A nutritional composition according to claim 14, further comprising one or more prebiotics. A method for improving resistance to milk allergy in pediatric subjects, wherein the nutritional composition comprises a carbohydrate source, a protein equivalent source, a fat or lipid source, a probiotic comprising Lactobacillus rhamnosus GG, and (i) a food butyrate ( ii) a component for stimulating endogenous butyrate; or (iii) providing at least one of a combination thereof.   The method of claim 18, wherein the nutritional composition comprises ingredients for stimulating endogenous butyrate production including polydextrose and galactooligosaccharides.   The method of claim 18, wherein the nutritional composition is an infant formula.