Use of human milk oligosaccharides in fattening calves

Abstract

To provide a use of human milk oligosaccharide for feeding a production animal such as a calf; a milk replacer composition containing human milk oligosaccharide; and a method of preventing and remedying a gastrointestinal disease, a gastrointestinal infectious disease in particular, of a young production animal, a calf in particular, by administering an effective dose of one or more kinds of human milk oligosaccharide.SOLUTION: Especially effective saccharide among the one or more kinds of human milk saccharide is 2'-fucosyllactose (2-FL).SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to the use of human milk oligosaccharides for feeding production animals, such as calves. The invention further relates to milk replacer compositions containing human milk oligosaccharides. A further subject of the invention is a method for preventing and treating gastrointestinal diseases, in particular gastrointestinal infections, in young production animals, especially calves, by administering an effective amount of one or more human milk oligosaccharides. Particularly useful in the context of the present invention is 2'-fucosyllactose (2-FL). [Background technology]

[0002] Raising healthy calves is the foundation for successful dairy farming. Healthy calves, achieved through optimal farm management and care, early development of gastroesophageal antral function, and economically prudent husbandry, are some of the goals of calf rearing (Steinwunder et al. (2005) Milchviehfutterung, Tier- und Leistungsgerecht. Leopold Stocker Verlag, Graz; Drochner, W. (2008): Futterung der Rinder. in: Jeroch et al. (eds.) Ernahrung landwirtschaftlicher Nutztiere, 2nd ed. Eugen Ulmer KG, Stuttgart, pp. 385-467).

[0003] Successful rearing is related to the minimization of animal losses, which is considered the most critical issue. In Germany, rearing losses have been in the range of 8-14% for several years (see, for example, Roehrmoser (1995): Aufzucht des Rindes. in: Matzke et al. (eds.) Wirtschaftliche Milchviehhaltung und Rindermast. 3rd ed., Frankfurt am Main, Verlag Union Agrar, pp. 221-261). The goal is to achieve losses of around 5%. Optimized calf feeding can contribute to this goal. Several preventive measures have been proposed in relation to feeding, for example to reduce diarrhea in calves (Schrag et al. (1984) Gesunde Kaelber - Gesunde Rinder. Die wichtigsten Krankheiten in Aufzucht und Mast. Erkennung, Vorbeuge, Behandlung. 3rd ed. Henbersberg, Schober Verlags-GmbH, pp 249-276). The focus of these measures is a well-developed intestinal flora and intestinal health. Various prebiotics have been proposed for inclusion in milk replacers to improve and maintain intestinal health (Dohms (2004) Aspekte der Darmgesundheit and Chancen fuer den Einsatz von Probiotic, 4th ed.).

[0004] Human milk oligosaccharides (HMOs) are a diverse family of non-conjugated glycans that are abundant and unique to human milk, as reviewed for example in Bode (2012) Glycobiology 22 (9), pp. 1147-1162.

[0005] WO-A-2012 / 158517 discloses the use of human milk oligosaccharides, particularly 2'-fucosyllactose, to promote the growth of bacteria found in the feces of infants. This prior art also contemplates the use of human milk oligosaccharides as prebiotics for the nutritional supplementation of various mammals. However, since no experimental data other than the promotion of the growth of intestinal bacteria is presented, the use of human milk oligosaccharides for feeding animals remains speculative. Summary of the Invention [Problem to be solved by the invention]

[0006] The technical problem underlying the present invention is to provide improved rearing of young production animals, especially calves, through improvements in the diet of such animals.

[0007] Solutions to the above technical problems are provided by embodiments of the present invention as described herein and defined in the claims. [Means for solving the problem]

[0008] In particular, the present invention relates to novel milk replacer compositions containing at least one human milk oligosaccharide.

[0009] According to the present invention, a "human milk oligosaccharide" is a sugar molecule composed of at least three carbohydrate entities, which sugar molecule is found in human milk or premilk from women. Preferably, the HMO is an oligosaccharide composed of 3, 4, 5, 6, 7, 8, 9, 10, or more sugar entities, whereby oligosaccharides containing four or more entities can be linear or branched oligomers. HMOs are typically composed of the monosaccharides glucose, galactose, N-acetylglucosamine, N-acetylgalactosamine, fucose, and N-acetylneuraminic acid. Most HMOs for use in the present invention are based on the disaccharides lactose or N-acetyllactosamine, with lactose-based ones being particularly preferred.

[0010] Preferred human milk oligosaccharides in the context of the present invention are 2'-fucoyl lactose (2-FL), 3'-fucosyllactose (3-FL), 3'-sialyllactose (3-SL), 6' These include, but are not limited to, sialyllactose (6-SL), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N-hexaose (LNH), iso-lacto-N-octaose, iso-lacto-N-neooctaose, para-lacto-N-octaose, lacto-N-fucopentaose I (LNFP I), lacto-N-fucopentaose II (LNFP II), lacto-N-fucopentaose III (LNFP III), lacto-N-fucopentaose V (LNFP V), LS-tetrasaccharide a (LST a), LS-zetrasaccharide b (LST b), LS-zetrasaccharide c (LST c), and disialyllacto-N-tetraose (DSLNT).

[0011] Particularly preferred HMOs for use in the present invention are the human milk trisaccharides 3-FL and 2-FL. Recently, biotechnological production of 2-FL has been provided (see WO-A-2010 / 070104), making this basic HMO available on an industrial scale (Jennewein Biotechnologie GmbH, Rheinbreitbach, Germany). Therefore, the HMO in the milk replacer composition is preferably a synthetic product, particularly prepared in bacterial culture using genetically modified bacteria as taught in WO-A-2010 / 070104, particularly the synthetic 2-FL described above; higher HMOs based on 2-FL are generally preferred in the context of the present invention, with 2-FL being the most preferred HMO for implementing the present invention.

[0012] The present invention also relates to milk replacer compositions containing more than one specific HMO. Thus, mixtures of two or more of the above HMOs are preferred. Particularly preferred are mixtures of HMOs, whereby one of the HMOs of the mixture contains both 2-FL and 3-FL, together with a third, fourth, fifth, etc. additional HMO. Most preferred in this context of the present invention is a combination of 2-FL and 3-FL.

[0013] The milk replacer compositions of the present invention can, of course, contain other sugars in addition to HMOs. In this context, lactose and N-acetyllactosamine should be mentioned as preferred further oligosaccharides.

[0014] "Milk replacer" or "milk replacer composition" refers to a nutritional composition for feeding production animals, preferably selected from cows, goats, sheep, pigs, deer and horses, in particular infants and young production animals. The terms "milk replacer" and "milk replacer composition" according to the present invention also include the definition according to Article 3(2) of Regulation (EC) No. 767 / 2009 of the European Parliament and of the Council, according to which "milk replacer" means "a compound feed administered in dry form or diluted with a given amount of liquid to supplement or replace milk, or to feed young animals, such as calves, lambs or kids intended for slaughter."

[0015] Thus, the milk replacer compositions of the present invention typically contain one or more HMOs as described above in addition to a basic milk replacer composition. The term milk replacer composition according to the present invention includes the composition in dry form as well as its liquid form, which is typically obtained by reconstituting said dry composition with water. Basic nutritional compositions for providing the milk replacer compositions of the present invention are known in the art (for a review of calf milk replacers, see, for example, online at: https: / / www.aphis.usda.gov / animaLheaIth / nahms / dairy / downIoads / bamn / BAGuideMilkRepl.pdf Bovine Alliance on Management and Nutrition (BAMN), 2008, A GUIDE TO CALF MILK REPLACERS; and Kamphues et al.

[0016] Thus, milk replacer compositions according to the invention generally comprise at least a protein and fat source, optionally reconstituted in an aqueous liquid (wherein the ingredients may be in the form of a suspension, emulsion and / or solution in an aqueous base), typically in admixture with further ingredients such as carbohydrates, fibre, vitamins, mineral supplements etc., and further additives such as medicinals, emulsifiers, thickeners, trace elements, antioxidants and flavourings.

[0017] Milk replacer compositions are usually classified according to the source of their protein and / or fat components. Typical protein sources for milk replacer compositions, particularly for use in feeding calves, include skim milk powder, whey powder, and vegetable protein sources, such as soy protein, soy flour, wheat gluten, or wheat isolate. The fat component of the milk replacer can be derived from animal fat or vegetable oil.

[0018] Both protein and fat levels are important characteristics of the milk replacer compositions for use in the present invention. The preferred protein level in a calf milk replacer is typically in the range of about 18 to about 22% (w / w), most preferably about 20% (w / w), and the fat level is preferably in the range of about 10 to about 28% (w / w). A fat level of about 18 to about 23% (w / w) is more preferred. The ingredient levels also vary depending on the type of animal being fed. For example, for breeding calves, the fat level typically ranges from about 13 to about 20% (w / w), while the fat content in the milk replacer composition should be increased to about 23% (w / w) for fattening calves. The calves were intended for slaughter. Another particular consideration in the preparation of milk replacer compositions is the carbohydrate-to-protein ratio. For example, pure dry whey has a lactose content of about 70% (w / w) and a protein content of about 12% (w / w). To implement the present invention, the content of carbohydrates (excluding HMO content), in particular lactose, glucose and sucrose, should preferably not exceed a value of 50% (w / w) in order to prevent high transit rates which would lead to colonic mis-fermentation.

[0019] A typical basic milk replacer composition for use in the present invention contains about 22% (w / w) or more crude protein, about 20% (w / w) or more crude fat, about 0.15% (w / w) or less crude fiber, calcium in an amount of about 0.75% (w / w) to about 1.75% (w / w), at least about 0.7% (w / w) phosphorus, at least about 20,000 lU / lb of vitamin A, at least about 5,000 lU / lb of vitamin D3, and about 100 lU / lb of vitamin E.

[0020] Milk replacer compositions according to the present invention typically contain HMOs (which may be a single type of HMO such as 2-FL, or a mixture of two or more different HMOs) in an amount of about 0.5-10.0% (w / w), preferably about 1-5% (w / w), and most preferably 4% (w / w), based on the total weight of the composition.

[0021] The present invention also relates to the use of one or more HMOs for feeding production animals, particularly young production animals such as calves, lambs, kids and foals, said HMOs being particularly useful in fattening calves.

[0022] The present invention also relates to a method for feeding production animals, particularly young production animals such as calves, lambs, kids, and foals. The method comprises feeding the production animals with the milk replacer composition of the present invention. The feeding method of the present invention improves the feed intake and performance parameters of the production animals, particularly with regard to calf fattening. As taught herein, a particular advantage of using HMOs as ingredients in milk replacer compositions is the improvement of the overall condition of the fed production animals, particularly calves, lambs, kids, and foals. As a result, the performance parameters of animals fed with the milk replacer of the present invention are improved. The milk replacer compositions of the present invention reduce animal losses, particularly by preventing gastrointestinal diseases, such as bacterial or viral intestinal infections that cause diarrhea. Without wishing to be bound by any theory, it is believed that the HMOs improve the growth of favorable intestinal bacteria, thereby reducing the relative number of pathogenic bacteria, while simultaneously preventing or at least impeding the binding of pathogenic substances, such as pathogenic intestinal bacteria and viruses, to intestinal receptors. HMOs are also thought to improve the animals' intestinal flora, modulate mucosal immunity, and enhance the animals' resistance to atopic conditions.

[0023] In the context of the present invention, HMOs are particularly useful for improving the health of production animals, such as calves, lambs, kids, and foals. In particular, HMOs (which can be administered alone or as a mixture of HMOs, as described above) are used to prevent and treat, and at least reduce the incidence of, gastrointestinal diseases, particularly bacterial and viral gastrointestinal diseases, such as diarrhea, in said production animals (or at least shorten the duration of such diseases). HMOs are also useful for preventing and treating, in production animals, preferably those defined above, atopic diseases, i.e., conditions associated with hypersensitivity to substances foreign to the body. Furthermore, HMOs are useful for improving mucosal immunity in production animals, particularly those mentioned above. According to the present invention, HMOs also improve the intestinal flora of production animals, such as calves, lambs, kids, and foals. HMOs can be administered alone or in the form of a composition, preferably in an oral dosage form, which can also take the form of a milk replacer composition as defined herein. The pharmaceutical composition can also take the form of a tablet or capsule that is given separately from any feed composition. Accordingly, the present invention is also directed to a method for preventing or treating gastrointestinal diseases, such as bacterial and viral infections in the gastrointestinal system, in a production animal, preferably a young production animal as outlined above. The method comprises administering to the production animal a safe and effective amount of a composition containing at least one HMO, or two or more HMOs. The present invention further relates to the use of a composition containing at least one HMO, or two or more HMOs, for the manufacture of a medicament for preventing or treating the above conditions. DETAILED DESCRIPTION OF THE INVENTION

[0024] The present invention is further illustrated by the following non-limiting examples.

[0025] Example Example 1: Feeding breeding calves with milk replacer containing HMOs Materials and Methods: Sixty Deutsche Holstein calves were divided into two groups (control and experimental, 30 each) with equal numbers of male (15 / 30) and female (15 / 30) animals. The average age of the calves was 7 days. Each animal in both groups was single-housed. At 14 days of age, the calves were divided into two groups, each housed in a different but otherwise identical stable. The animals were fed a milk replacer composition via an automatic water dispenser. The animals had free access to water from a water dispenser. In addition, each animal was given 150 g of hay per day. From the 8th week onwards, concentrates were provided via an automated dispenser. Both groups, with the exception of the HMO, received the same milk replacer composition. The experimental group received a basic maternal milk replacer composition plus 4% (w / w) 2-FL. The control group received an additional 4% (w / w) whey powder instead of the HMO. One liter of liquid milk replacer composition contains 125 g of dry milk replacer concentrate.

[0026] The following table shows the feeding schedule: [Table 1]

[0027] Experimental period: 77 days

[0028] Data collection: Feeding by automatic dispenser with single-animal recognition, measurement of food intake by each individual; hay and feed concentrate data collected by weighing; daily weighing of each animal; sublingual measurement of body temperature at the automatic feed dispenser and weekly rectal measurement for comparison and control; health monitoring and medication use; weekly analysis of feces for enteric bacterial colonization.

[0029] Feed analysis, milk replacer, hay and feed concentrate analysis.

[0030] Example 2: Feeding fattening cattle with milk replacer containing HMOs Materials and Methods: Sixty Fleckvieh calves were divided into two groups (control / experimental) of 30 calves each. Both groups contained an equal number of male (15 / 30) and female (15 / 30) calves. The average age of the animals was 14 days (live weight 50-60 kg). Animals in each group were housed in identical stables. The animals were fed a milk replacer composition via an automatic water dispenser. The animals had free access to water. In addition, each animal received 300 g of hay per day. Both groups, except for HMO, received the same milk replacer composition. The experimental group received a basic maternal milk replacer composition plus 4% (w / w) 2-FL. The control group received an additional 4% (w / w) whey powder instead of HMO. At the start of the experiment, 1 liter of liquid feed composition contained 125 g of dry milk replacer concentrate. At the end of the experiment, the concentration of the liquid feed composition is increased to 250 g per liter.

[0031] The feeding plan is as follows: [Table 2]

[0032] Duration of the experiment: The experiment will begin at approximately 14 days of age and will end with the animals being killed at a weight of approximately 230-240 kg (22nd week of the experiment), for a duration of approximately 140 days.

[0033] Data collection: Feeding by automatic dispensers with single animal recognition, measurement of food intake by each individual; hay and feed concentrate data collected by weighing; daily weighing of each animal; sublingual measurement of body temperature at the automatic feed dispenser and weekly rectal measurement for comparison and control; health monitoring and medication use; weekly analysis of feces for enteric colonization. After sacrifice, each animal's body is evaluated.

[0034] Feed analysis, milk replacer and hay analysis.

Claims

1. A 2'-fucosyllactose-containing milk replacer composition for use in preventing gastrointestinal diseases in a production animal selected from the group consisting of calves, lambs, kids and foals, wherein the 2'-fucosyllactose improves the growth of intestinal bacteria, thereby reducing the relative number of pathogenic bacteria, thereby preventing or at least interfering with the binding of pathogenic intestinal bacteria to intestinal receptors in the production animal, wherein the 2'-fucosyllactose is prepared by bacterial culture, and the content of carbohydrates excluding human milk oligosaccharides in the 2'-fucosyllactose-containing milk replacer composition is 50% (w / w) or less.

2. 2'-fucosyllactose-containing milk replacer composition according to claim 1, which is used for fattening calves.

3. Use of the 2'-fucosyllactose-containing milk substitute composition described in claim 1.

4. The use according to claim 3, which is used for fattening calves.

5. A method for treating or preventing gastrointestinal diseases in a production animal, comprising feeding the production animal the 2'-fucosyllactose-containing milk replacer composition described in claim 1.

6. A method for feeding a production animal, comprising feeding the production animal the 2'-fucosyllactose-containing milk replacer composition described in claim 1.

7. 7. The method of claim 5 or 6, wherein the production animals are calves used for fattening.

8. 2'-fucosyllactose-containing milk substitute composition according to claim 1, wherein 2'-fucosyllactose is contained in an amount of 0.5 to 10.0% by mass of the total mass of the milk substitute composition.

9. 2'-fucosyllactose-containing milk substitute composition according to claim 1, wherein 2'-fucosyllactose is contained in an amount of 1.0 to 5.0% by mass of the total mass of the milk substitute composition.

10. 2'-fucosyllactose-containing milk substitute composition according to claim 1, wherein 2'-fucosyllactose is contained in an amount of 4.0% by mass of the total mass of the milk substitute composition.

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