CN109788781A - 人乳低聚糖在犊牛育肥中的用途 - Google Patents
人乳低聚糖在犊牛育肥中的用途 Download PDFInfo
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- CN109788781A CN109788781A CN201780052697.9A CN201780052697A CN109788781A CN 109788781 A CN109788781 A CN 109788781A CN 201780052697 A CN201780052697 A CN 201780052697A CN 109788781 A CN109788781 A CN 109788781A
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- human milk
- calf
- milk oligosaccharides
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- A—HUMAN NECESSITIES
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Landscapes
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Abstract
本发明涉及人乳低聚糖用于饲喂诸如犊牛等生产动物的用途。本发明还涉及含有人乳低聚糖的代乳品组合物。本发明的另一主题是通过施用有效量的一种或多种人乳低聚糖来预防和治疗幼年生产动物(特别是犊牛)的胃肠疾病(特别是胃肠感染)的方法。在本发明的背景下作为一种或所述人乳低聚糖特别有用的是2’‑岩藻糖基乳糖(2‑FL)。
Description
本发明涉及人乳低聚糖用于饲喂诸如犊牛等生产动物的用途。本发明还涉及包含人乳低聚糖的代乳品组合物。本发明的另一主题是通过施用有效量的一种或多种人乳低聚糖来预防和治疗幼年生产动物(特别是犊牛)的胃肠疾病(特别是胃肠感染)的方法。在本发明的背景下作为一种或所述人乳低聚糖特别有用的是2’-岩藻糖基乳糖(2-FL)。
健康犊牛的饲养是乳牛业成功的基础。通过最佳农业和护理获得的健康犊牛、胃食管前庭功能的早期发展和经济合理的饲养是犊牛饲养的几个目标(Steinwunder等(2005)Milchviehfütterung,Tier- und Leistungsgerecht.Leopold Stocker Verlag,Graz；Drochner,W.(2008):Fütterung der Rinder.in:Jeroch等(编)Ernahrunglandwirtschaftlicher Nutztiere,第2版.Eugen Ulmer KG,Stuttgart,385-467页)。
成功饲养与动物损失的最小化有关，这被认为是最关键的问题。在德国，几年来增加的损失在8％至14％之间(参见，例如，(1995):Aufzucht des Rindes.in:Matzke等(编)Wirtschaftliche Milchviehhaltung und Rindermast.第3版,Frankfurtam Main,Verlag Union Agrar,221-261页)。目标应该达到约5％的损失。优化的犊牛饲喂可以有助于实现这一目标。在饲喂方面已经提出了几种预防措施，例如减少犊牛腹泻的情况(Schrag等(1984)GesundeRinder.Die wichtigsten Krankheiten inAufzucht und Mast.Erkennung,Vorbeuge,Behandlung.第3版.Henbersberg,SchoberVerlags-GmbH,249-276页)。这些措施的焦点是发育良好的肠道微生物群和肠道的健康状况。已经提出在代乳品中包含各种益生元以改善和维持肠道健康(Dohms(2004)Aspekteder Darmgesundheit und Chancen fur den Einsatz von Probiotika,第4版)。
人乳低聚糖(HMO)是丰富且对人乳而言是独特的多样未结合的聚糖一族；例如在以下所综述：Bode(2012)Glycobiology 22(9)，1147-1162页。
WO-A-2012/158517公开了人乳低聚糖、特别是2’-岩藻糖基乳糖用于促进婴儿粪便中发现的细菌生长的用途。该现有技术还打算使用人乳低聚糖作为益生元用于多种哺乳动物的营养，然而，除了肠杆菌的生长促进之外，没有提供任何实验数据，因此使用人乳低聚糖饲喂动物仍然是推测性的。
本发明所要解决的技术问题是提供幼年生产动物、特别是犊牛的改善的饲养，特别是通过改善它们的饲喂。
上述技术问题的解决方案由本文所述的本发明的实施方式提供，并且如权利要求中所限定。
特别是，本发明涉及包含至少一种人乳寡糖的新型代乳品组合物。
根据本发明，“人乳低聚糖”是由至少三个碳水化合物实体组成的糖分子，该糖分子存在于女性的乳汁或预乳中。优选地，HMO是由3、4、5、6、7、8、9、10或更多个糖实体组成的低聚糖，其中包含4个以上实体的低聚糖可以是直链或支链低聚物。HMO通常由单糖葡萄糖、半乳糖、N-乙酰葡糖胺、N-乙酰乳糖胺、岩藻糖和N-乙酰神经氨酸组成。用于本发明的大部分HMO基于二糖乳糖或N-乙酰乳糖胺，特别优选基于乳糖的HMO。
在本发明的背景下，优选的人乳低聚糖包括但不限于2’-岩藻糖基乳糖(2-FL)、3’-岩藻糖基乳糖(3-FL)、3’-唾液酸乳糖(3-SL)、6’-唾液酸乳糖(6-SL)、乳-N-四糖(LNT)、乳-N-新四糖(LNnT)、乳-N-六糖(LNH)、异乳-N-八糖、异乳-N-新八糖、对乳-N-八糖、乳-N-岩藻五糖I(LNFP I)、乳-N-岩藻五糖II(LNFP II)、乳-N-岩藻五糖III(LNFP III)、乳-N-岩藻五糖V(LNFP V)、LS-四糖a(LST a)、LS-四糖b(LST b)、LS-四糖c(LST c)和二唾液酸乳-N-四糖(DSLNT)。
用于本发明的特别优选的HMO是人乳三糖3-FL和2-FL。最近，已经提供了2-FL的生物技术生产(参见WO-A-2010/070104)，使得该基础HMO可以工业规模获得(JenneweinBiotechnologie GmbH，Rheinbreitbach，德国)。因此，代乳品组合物中的HMO优选是在细菌培养中制备的合成HMO，特别是使用WO-A-2010/070104中教导的遗传修饰的细菌。在本发明的背景下，2-FL，特别是如前所述的合成2-FL，和基于2-FL的更高HMO通常是优选的，并且2-FL是用于实施本发明的最优选的HMO。
本发明还涉及包含多于一种的特定HMO的代乳品组合物，其中优选两种以上上述HMO的混合物。特别优选的是如下的HMO混合物，其中混合物中的一种HMO是2-FL或3-FL，或者该混合物包含2-FL和3-FL以及第三种、第四种、第五种等其他HMO。在本发明的背景下，最优选的是2-FL和3-FL的组合。
当然，本发明的代乳品组合物还可以包含除HMO外的其他糖。在本文中，提及乳糖和N-乙酰乳糖胺作为优选的其他低聚糖。
“代乳品”或“代乳品组合物”是指用于饲喂生产动物的营养组合物，所述生产动物优选选自牛、山羊、绵羊、猪、鹿和马，尤其是婴儿和幼年生产动物。根据本发明，术语“代乳品”和“代乳品组合物”还包括根据欧洲议会和理事会(EC)767/2009号条例第3(2)条规定的定义，其中“代乳品”是指“复合饲料，其以干燥形式或在给定量的液体稀释后施用，作为后乳汁的补充或替代用于饲喂幼年动物，或用于饲喂诸如用于屠宰的犊牛、羔羊或小山羊等幼年动物”。
因此，本发明的代乳品组合物通常包含一种或多种如上所述的HMO以及基础代乳品组合物。本发明的术语代乳品组合物包含干燥形式以及其液体形式的组合物，液体形式通常通过用水重构干燥组合物而获得。用于提供本发明的代乳品组合物的基础营养组合物是本领域已知的(关于犊牛代乳品的概述，参见，例如Bovine Alliance on Managementand Nutrition(BAMN),2008,A GUIDE TO CALF MILK REPLACERS，在线访问https://www.aphis.usda.gov/animal_health/nahms/dairy/downloads/bamn/BAMN08_GuideMilkRepl.pdf；和Kamphues等(2004)Supplemente zu Vorlesungen und Ubungen inder Tierernahrung,Hannover,Verlag M.&H.Schaper Alfred)。
因此，本发明的代乳品组合物通常至少包含蛋白质和脂肪源，其可选地在含水液体中重构(其中成分可以以悬浮液、乳液和/或溶液的形式存在于水基中)，通常与诸如碳水化合物、纤维、维生素、矿物质补充剂等其他成分以及诸如药物、乳化剂、增稠剂、微量元素、抗氧化剂和调味剂等其他添加剂混合。
代乳品组合物通常根据其蛋白质和/或脂肪成分的来源分类。特别是用于犊牛饲喂的代乳品组合物的典型蛋白质来源包括脱脂奶粉、乳清粉和植物蛋白源如大豆蛋白、大豆粉、小麦面筋或小麦分离物。代乳品的脂肪成分可以来自动物脂肪或植物油。
蛋白质和脂肪水平均是本发明中使用的代乳品组合物的重要特征。犊牛代乳品中优选的蛋白质水平通常为约18％重量％～约22重量％，最优选为约20重量％，脂肪水平优选为约10％重量％～约28重量％，更优选为约18％重量％～约23重量％的脂肪。成分的水平也随待饲喂动物的类型而变化。例如，对于繁殖用犊牛，脂肪水平通常为约13％重量％～约20重量％，而对于育肥犊牛(即用于屠宰的犊牛)，代乳品组合物中的脂肪水平应当提高至约23重量％。生产代乳品组合物的特殊考虑因素还有碳水化合物与蛋白质的比。例如，纯干燥乳清的乳糖含量为约70重量％，蛋白质含量为约12重量％。为了实施本发明，碳水化合物，特别是乳糖、葡萄糖和蔗糖的含量(不包括HMO含量)应当优选不超过约50重量％的值，以防止高通过率导致结肠中的不当发酵(Kamphues(2004)，同上)。
用于本发明的典型的基础代乳品组合物包含约22重量％以上的粗蛋白，约20重量％以上的粗脂肪，不多于约0.15重量％的粗纤维，约0.75重量％～约1.75重量％的量的钙，至少约0.7重量％的磷，至少约20000IU/Ib的维生素A，至少约5000IU/Ib的维生素D3，和约100IU/Ib的维生素E。
基于组合物的总重量，根据本发明的代乳品组合物通常包含约0.5重量％～10.0重量％，优选约1重量％～5重量％，最优选4重量％的量的HMO(其可以是单一类型的HMO，如2-FL，或2种以上不同HMO的混合物)。
本发明还涉及HMO(一种或多种HMO)用于饲喂生产动物特别是诸如犊牛、羊羔、小山羊和马驹等幼年生产动物的用途。HMO在犊牛育肥中特别有用。
本发明还涉及一种饲喂生产动物特别是诸如犊牛、羊羔、小山羊和马驹等幼年生产动物的方法，其包括向生产动物饲喂本发明的代乳品组合物的步骤。本发明的饲喂方法改善了生产动物的采食量和性能参数，特别是在犊牛育肥的情况下。使用HMO作为如本文所教导的代乳品组合物中的成分的特殊益处在于改善了饲喂的生产动物特别是犊牛、羊羔、小山羊和马驹的总体条件，从而用根据本发明的代乳品饲喂的动物的性能参数得到改善。本发明的代乳品组合物减少了动物的损失，特别是通过预防导致腹泻的肠道疾病，例如细菌或病毒肠道感染。不希望受任何理论束缚，据信HMO改善有益肠道细菌的生长，从而减少病原菌的相对数量，同时防止或至少阻碍诸如病原性肠杆菌和病毒等病原体与肠道受体的结合。HMO也被认为改善动物的肠道微生物群，调节粘膜免疫力，并增强动物对特应性病况的抵抗力。
在本发明的背景下，HMO在改善诸如犊牛、羊羔、小山羊和马驹等生产动物的健康中是特别有用的。特别是，HMO(如上所述，其可以单独给予或者可以作为HMO的混合物提供)用于在所述生产动物中预防和治疗并且至少减少胃肠疾病特别是细菌和病毒性胃肠疾病(如腹泻)的发生(或至少缩短这些疾病的时间)。HMO在预防和治疗生产动物(优选如上定义的那些)中的特应性疾病也是有用的，特应性疾病即身体对外来物质的超敏反应相关的病况。此外，HMO对于改善生产动物(特别是前面提到的那些)的粘膜免疫力是有用的。根据本发明，HMO还改善了诸如犊牛、羊羔、小山羊和马驹等生产动物的肠道菌群。HMO可以单独施用或以组合物的形式施用，优选以口服施用形式，其也可以采取如本文定义的代乳品组合物的形式。药物组合物还可以采取与任何饲喂组合物分开给予的片剂或胶囊的形式。因此，本发明还涉及用于在生产动物(优选如上所述的幼年生产动物)中预防或治疗胃肠疾病(例如胃肠系统中的细菌和病毒性感染，例如腹泻)的方法，该方法包括向生产动物施用安全有效量的至少一种HMO或含有两种以上HMO的组合物的步骤。本发明还涉及至少一种HMO或含有两种以上HMO的组合物在制备用于预防或治疗上述病况的药物中的用途。
通过以下非限制性实施例进一步说明本发明：
实施例
实施例1：使用含有HMO的代乳品饲喂繁殖用犊牛
材料和方法：将60只犊牛(Deutsche Holstein)分为两组(对照组和实验组，每组30只)，其具有等量的雄性(15/30)和雌性(15/30)动物。犊牛的平均年龄是7日。两组中的每只动物都保持单独饲喂。在14日龄时，犊牛被分成两组，每组保持在不同但其他方面相同的牛棚中。通过自动饮水机向动物饲喂代乳品组合物。动物可以从饮水机自由取水。此外，每只动物每天给予150g干草。从第8周开始，通过自动分配器给予浓缩饲料。除HMO外，两组都用相同的代乳品组合物饲喂。实验组饲喂基础代乳品组合物加4重量％2-FL。对照组用额外的4重量％乳清粉代替HMO进行饲喂。1升液体代乳品组合物含有125g干代乳品浓缩物。
下表显示了饲喂方案：
| 年龄 | 饲料 | 体积(升) | 牛棚 |
| 第1周 | 初乳 | 单个 | |
| 第2周 | 2×3升代乳品或代乳品+HMO | 42 | 单个 |
| 第3周至第7周 | 2×3升代乳品或代乳品+HMO | 210 | 组 |
| 第8周至第10周 | 2×2升代乳品或代乳品+HMO | 56 | 组 |
| 第10周至第12周 | 1×3升代乳品或代乳品+HMO | 28 | 组 |
| 总计：336 |
实验持续时间：77天
数据收集：通过自动分配器饲喂，其具有单个动物识别，测量每个个体的食物摄入量；通过称重收集干草和饲料浓缩物数据；每只动物每日称重；在自动饲喂分配器处舌下测量体温，每周一次直肠测量，以进行比较和控制；控制健康状况和使用药物；对于肠道细菌定植的粪便每周分析。
饲料分析。代乳品、干草和饲料浓缩物的分析。
实施例2：使用含有HMO的代乳品饲喂育肥犊牛
材料和方法：将60只繁殖用Fleckvieh犊牛分为两组(对照/实验)，每组30只犊牛。两组中均含有等量的雄性(15/30)和雌性(15/30)犊牛。动物的平均年龄为14日(活体重50kg～60kg)。每组动物保持在牛棚中，两个牛棚是相同的。通过自动饮水机向动物饲喂代乳品组合物。动物可以自由地取水。此外，每只动物每天给予300g干草。除HMO外，两组都用相同的代乳品组合物饲喂。实验组饲喂基础代乳品组合物加4重量％2-FL。对照组用额外的4重量％乳清粉代替HMO进行饲喂。在实验开始时，1升液体饲料组合物包含125g干代乳品浓缩物。在实验结束时，液体进料组合物的浓度增加至250g/升。
饲喂方案如下：
实验持续时间：实验在约14日龄开始，最后屠宰重量为约230kg～240kg(约实验的第22周)，持续时间约140天。
数据收集：通过自动分配器饲喂，其具有单个动物识别，测量每个个体的食物摄入量；通过称重收集干草和饲料浓缩物数据；每只动物每日称重；在自动饲喂分配器处舌下测量体温，每周一次直肠测量，以进行比较和控制；控制健康状况和使用药物；对于肠道细菌定植的粪便每周分析。屠宰后，评估每只动物的身体。
饲料分析。代乳品和干草的分析。
Claims (14)
1.代乳品组合物，其含有至少一种人乳低聚糖。
2.如权利要求1所述的组合物，其中，所述低聚糖是2’-岩藻糖基乳糖。
3.如权利要求1或2所述的组合物，基于所述组合物的总重量，其含有0.5重量％～10.0重量％的量的所述人乳低聚糖。
4.如权利要求3所述的组合物，基于所述组合物的总重量，其含有1.0重量％～5.0重量％的量的所述人乳低聚糖。
5.如权利要求4所述的组合物，基于所述组合物的总重量，其含有4.0重量％的量的所述人乳低聚糖。
6.如前述权利要求中任一项所述的组合物，其中，所述人乳低聚糖是在细菌培养中制备的合成低聚糖。
7.一种或多种人乳低聚糖在生产动物的饲喂中的用途。
8.如权利要求7所述的用途，其中，所述人乳低聚糖用于犊牛。
9.如权利要求8所述的用途，其中，所述人低聚糖是2’-岩藻糖基乳糖。
10.一种用于预防生产动物的胃肠疾病的人乳低聚糖或人乳低聚糖的组合物。
11.如权利要求10所述的人乳低聚糖，其中，所述生产动物是犊牛。
12.如权利要求11所述的人乳低聚糖，其中，所述低聚糖是2’-岩藻糖基乳糖。
13.一种饲喂生产动物的方法，其包括向所述生产动物饲喂权利要求1～6中任一项所述的代乳品组合物的步骤。
14.如权利要求13所述的方法，其中，所述动物是犊牛。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP16186533.2 | 2016-08-31 | ||
| EP16186533 | 2016-08-31 | ||
| PCT/EP2017/071606 WO2018041803A1 (en) | 2016-08-31 | 2017-08-29 | Use of human milk oligosaccharides in calves fattening |
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| JP (2) | JP2019528088A (zh) |
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| CA (1) | CA3035290A1 (zh) |
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| US20220226382A1 (en) * | 2019-06-05 | 2022-07-21 | Morinaga Milk Industry Co., Ltd. | Nutritional Composition |
| WO2020246583A1 (ja) * | 2019-06-05 | 2020-12-10 | 森永乳業株式会社 | 組成物 |
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| WO2010120682A1 (en) * | 2009-04-13 | 2010-10-21 | Morrow Ardythe L | Milk oligosaccharide compositions and use thereof in treating infection in animals |
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| US20020019991A1 (en) * | 1998-04-30 | 2002-02-14 | Abbott Laboratories | Compositions containing an alpha 1,2-fucose linkage and uses thereof |
| US20080003329A1 (en) * | 2006-06-30 | 2008-01-03 | Ricardo Rueda | Enriched infant formulas |
| CN102257128A (zh) | 2008-12-19 | 2011-11-23 | 詹内怀恩生物技术股份有限公司 | 岩藻糖化化合物的合成 |
| CA2824960A1 (en) * | 2011-02-04 | 2012-08-09 | The Regents Of The University Of California | Disialyllacto-n-tetraose (dslnt) or variants, isomers, analogs and derivatives thereof to prevent or inhibit bowel disease |
| CA2827313C (en) * | 2011-02-16 | 2023-08-22 | Glycosyn LLC | Biosynthesis of human milk oligosaccharides in engineered bacteria |
| WO2012158517A1 (en) | 2011-05-13 | 2012-11-22 | Glycosyn LLC | The use of purified 2'-fucosyllactose, 3-fucosyllactose and lactodifucotetraose as prebiotics |
| NL2007931C2 (en) * | 2011-12-07 | 2013-06-10 | Friesland Brands Bv | Methods for providing sialylated oligosaccharides and products obtainable thereby. |
| AU2014350156A1 (en) * | 2013-11-15 | 2016-04-14 | Nestec S.A. | Compositions for use in the prevention or treatment of necrotizing enterocolitis in infants or young children born by C-section |
| KR20170052631A (ko) * | 2014-09-12 | 2017-05-12 | 바스프 에스이 | 2＇-o-푸코실락토오스의 제조 방법 |
| SG11201811227QA (en) * | 2016-07-01 | 2019-01-30 | Evolve Biosystems Inc | Method for facilitating maturation of the mammalian immune system |
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- 2017-08-29 KR KR1020247002832A patent/KR20240016454A/ko not_active Application Discontinuation
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- 2017-08-29 BR BR112019003890-6A patent/BR112019003890A2/pt not_active Application Discontinuation
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010120682A1 (en) * | 2009-04-13 | 2010-10-21 | Morrow Ardythe L | Milk oligosaccharide compositions and use thereof in treating infection in animals |
Non-Patent Citations (1)
| Title |
|---|
| CILIEBORG ETC.: "Minimal short-term effect of dietary 2"-fucosyllactose on bacterial colonisation,intestinal function and necrotising enterocolitis in preterm pigs", 《 BRITISH JOURNAL OF NUTRITION》 * |
Also Published As
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| EP3506768A1 (en) | 2019-07-10 |
| KR20190045228A (ko) | 2019-05-02 |
| WO2018041803A1 (en) | 2018-03-08 |
| BR112019003890A2 (pt) | 2019-05-21 |
| US20190183145A1 (en) | 2019-06-20 |
| US20210212342A1 (en) | 2021-07-15 |
| MX2019002386A (es) | 2019-06-20 |
| KR20240016454A (ko) | 2024-02-06 |
| JP2019528088A (ja) | 2019-10-10 |
| JP2023123516A (ja) | 2023-09-05 |
| AU2017318386A1 (en) | 2019-03-21 |
| AU2022204538A1 (en) | 2022-07-21 |
| CA3035290A1 (en) | 2018-03-08 |
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