CN113367243A - 一种保护仔猪肠道健康的添加剂 - Google Patents
一种保护仔猪肠道健康的添加剂 Download PDFInfo
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- CN113367243A CN113367243A CN202110654948.9A CN202110654948A CN113367243A CN 113367243 A CN113367243 A CN 113367243A CN 202110654948 A CN202110654948 A CN 202110654948A CN 113367243 A CN113367243 A CN 113367243A
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Abstract
本发明公开了一种保护仔猪肠道健康的添加剂，添加剂为微胶囊包被的组合物，组合物包含丁酸或/和丁酸盐与烟酸或/和烟酰胺组成，组合物中组份的质量之比为100:1‑100:8，且在微胶囊中的质量比为20%‑40%。组合物复合包被后，比单一添加任意一种单一成分，效果更好，从而减少每一种添加剂的用量，节约成本。使用该添加剂预混料能显著保护仔猪肠道健康、抑制仔猪肠道炎症，从而提高仔猪生长性能。
Description
技术领域
本发明涉及仔猪饲料添加剂领域，具体涉及一种保护仔猪肠道健康的饲料添加剂。
背景技术
仔猪断奶后由于肠道功能发育不完全，肠道免疫力较低，肠细胞能量供给不足，从而导致仔猪肠道粘膜损伤、肠道功能紊乱，易发生严重腹泻和生长受阻，常常出现食欲不振、消化功能减弱，致使仔猪对养分的消化吸收率降低，免疫力下降，饲料报酬随之降低，而影响仔猪的生产性能。目前研究保护和提高仔猪肠道健康的技术很多，有采用添加益生菌方案的，专利申请CN202010338893.6公开一种提高断奶仔猪肠道健康的复合饲料，包括甘露寡糖、由枯草芽孢杆菌、酿酒酵母、丁酸梭菌和解淀粉芽孢杆菌组成复合益生菌和基础饲料，该饲料对仔猪肠道菌群结构有正面影响；有采用中草药方案的，专利申请CN201710139850.3公开一种调节仔猪肠道健康中草药组合物包括苍术、白术、干姜、陈皮、焦山楂、焦神曲、焦麦芽组成，结果显示添加二术三仙散，可以改善仔猪肠道形态和肠道菌群，促进肠道健康效果显著。有增加基础营养方案的，专利申请CN201210164947.7公开大豆蛋白∶谷物蛋白∶动物蛋白重量比为7∶3∶1蛋白源能够显著提高断奶仔猪的生产性能，改善其机体代谢状况，并有提高仔猪机体合成激素胰岛素水平的趋势，对断奶仔猪肠道空肠粘膜营养物质消化酶活也有一定的影响。
丁酸或丁酸盐能够增强断奶仔猪肠道免疫力，缓解腹泻和促进生长。但在生产实践中丁酸或丁酸盐产品因是否包被应用效果不稳定、差异大，除了产品的生产工艺外，可能还存在其他内在影响因素。饲料中添加烟酸或烟酰胺主要是利用其作为维生素的功能。但丁酸或/和丁酸盐与烟酸或/和烟酰胺，协同调控动物肠道免疫功能缺乏相关的研究。
发明内容
本发明所要解决的技术问题是提供一种保护仔猪肠道健康的饲料添加剂，本发明提供的添加剂能够很好的保护仔猪的肠道健康，提高仔猪采食量和日增重，降低其腹泻率，保障了仔猪的健康和正常生长，提高养殖场的经济效益。
为解决上述问题，本发明提供了一种保护仔猪肠道健康的添加剂，所述添加剂为微胶囊包被的组合物，其组合物包含丁酸或/和丁酸盐与烟酸或/和烟酰胺，其质量之比为100:1-100:8，且在微胶囊中的质量比为20%-40%。微胶囊包被的组合物中丁酸盐中金属离子为锂、钠、钾。按照现有方法制备微胶囊组合物。本发明提供的添加剂利用复合包被技术，能够保证丁酸或/和丁酸盐与烟酸或/和烟酰胺按照最佳添加比例到达后肠，特别是大肠，能够安全、高效地保护仔猪肠道健康，改善肠道菌群。
烟酸-丁酸协同通过三种方式调控动物肠道免疫功能，一是GPR109A介导烟酸-丁酸调控肠道免疫，烟酸-丁酸对肠道粘膜免疫功能具有重要的调控作用，烟酸是肠道微生物的重要代谢产物，控制着体内烟酰胺腺嘌呤二核苷酸浓度，在肠道能量代谢和免疫功能方面发挥重要作用，能够降低DSS诱导结肠炎小鼠肠道MPO、TNF-α等炎症因子的表达,添加烟酰胺或烟酸显著提高小肠上皮细胞抗菌肽的表达，缓解色氨酸缺乏或者ACE2敲除小鼠肠道炎症和腹泻。烟酸和丁酸在肠道粘膜中共用GPR109A，且肠上皮细胞和免疫细胞均存在GPR109A。GPR109A在肠道抗原呈递细胞中具有抗炎作用，敲除GPR109A的小鼠易患结肠炎。研究发现，烟酸-丁酸通过GPR109A识别后提高树突状细胞和巨噬细胞产生抗炎因子IL-10，进而诱导调节性T细胞产生和抑制Th17细胞，同时在肠道上皮细胞经GPR109A受体识别后提高IL-18表达，从而促进肠道粘膜损伤修复；二是通过能量代谢影响肠道免疫，烟酸-丁酸在肠细胞能量代谢中发挥重要作用。丁酸可在结肠中被大量吸收，约占结肠耗氧量的60%-70%，可作为结肠上皮细胞的能量来源。丁酸也能通过提高胰岛素敏感性，加剧脂肪酸氧化，通过“肠-脑轴”激活肠道糖异生作用等途径调节能量代谢。烟酸是辅酶NAD+和NADP的组成成分，参与细胞脂质代谢、呼吸的氧化过程和糖类无氧分解等过程。研究表明，丁酸处理后的巨噬细胞胞外酸化率降低，能量代谢得到改善，诱导具有较强抗菌活性的巨噬细胞分化，调节机体免疫；三是调控组蛋白乙酰化影响肠道免疫，蛋白是染色质重复单元核小体的重要组成部分，组蛋白修饰能够精准调控固有免疫反应和相应防御基因的表达。在组蛋白修饰方式中，组蛋白乙酰化对细胞炎症因子、抗菌肽等转录调控发挥关键作用。研究发现，HDACs抑制剂可以显著提高染菌与正常的人结肠Caco-2细胞中的抗菌肽AMP的表达，且不影响促炎细胞因子基因的表达。丁酸盐作为组蛋白去乙酰化酶抑制剂，通过抑制HDAC3促进单核细胞向巨噬细胞分化，诱导小肠巨噬细胞产生抗菌活性物质，增强对肠道致病菌的抵抗力。SIRTs是NAD+依赖的去乙酰酶，广泛表达于小肠和结肠等肠上皮细胞，能够调控组蛋白和非组蛋白的乙酰化，包括NF-κB、AP-1、MAPK等蛋白的乙酰化，进而调控肠道免疫因子的转录。烟酸或烟酰胺可通过调节NAD/NADH比值而调控SIRTs的活性。在应激状态下，增加NAD+合成可以激活SIRT1，促进肠道干细胞更新，改善肠道粘膜屏障损伤修复。HDACs与SIRTs在调控细胞免疫反应中存在交互作用。
本发明提供的添加剂，其组合物丁酸或/和丁酸盐与烟酸或/和烟酰胺，按照复合包被，保证组份中成分能到达至指定位置按照最佳比例释放，通过GPR109A受体、能量代谢、组蛋白乙酰化修饰等途径协同调控仔猪肠道(特别是大肠)微生物和免疫稳态的重要因素，从而达到保护仔猪肠道，提高仔猪的生长性能。
附图说明
图1为应用例的代谢组学及16S生物信息分析结果图。1A：粪便短链脂肪酸代谢统计图；1B：结肠16S分析统计图；1C：粪便16S分析统计图。
图2为实施例的S100A8、TNF-α、IL-4基因qPCR检测分析结果统计图。2A：S100A8基因分析；2B：TNF-α基因分析；2C：IL-4基因分析。
具体实施方式
以下列举具体实施例对本发明进行说明，实施例只用于对本发明作进一步说明，不代表本发明的保护范围，其他人根据本发明做出的非本质的修改和调整，仍属于本发明的保护范围。
实施例1
一种保护仔猪肠道健康的添加剂，按照质量比100:1，丁酸2000mg和烟酰胺20mg，混合均匀。按照现有微胶囊化的方法，将羟丙基甲基纤维素、壳聚糖和二氧化硅混合并在流化床中230℃高温沸腾膨胀，得到混合物，然后将丁酸和烟酰胺的水溶液喷涂到上述混合物上，高温干燥后低温固化，使组合物颗粒固化成型，然后将包膜材料巴西棕榈蜡、棕榈油脂和聚乙二醇溶于有机溶剂，在流化床中进行底喷包衣，得到包膜均匀的丁酸-烟酰胺颗粒，组合物含量20%。
实施例2
一种保护仔猪肠道健康的添加剂，按照质量比100:2，丁酸钠2000mg和烟酸40mg，混合均匀。按照现有微胶囊化的方法，将羟丙基甲基纤维素、壳聚糖和二氧化硅混合并在流化床中230℃高温沸腾膨胀，得到混合物，然后将丁酸钠和烟酸的水溶液喷涂到上述混合物上，高温干燥后低温固化，使组合物颗粒固化成型，然后将包膜材料巴西棕榈蜡、棕榈油脂和聚乙二醇溶于有机溶剂，在流化床中进行底喷包衣，得到包膜均匀的丁酸钠-烟酸颗粒，组合物含量30%。
实施例3
一种保护仔猪肠道健康的添加剂，按照质量比100:4，丁酸1000mg、丁酸锂1000mg和烟酰胺40mg、烟酸40mg，混合均匀。按照现有微胶囊化的方法，将羟丙基甲基纤维素、壳聚糖和二氧化硅混合并在流化床中230℃高温沸腾膨胀，得到混合物，然后将丁酸、丁酸钠、烟酰胺和烟酸的水溶液喷涂到上述混合物上，高温干燥后低温固化，使组合物颗粒固化成型，然后将包膜材料巴西棕榈蜡、棕榈油脂和聚乙二醇溶于有机溶剂，在流化床中进行底喷包衣，得到包膜均匀的丁酸-丁酸锂-烟酰胺-烟酸颗粒，组合物含量40%。
实施例4
一种保护仔猪肠道健康的添加剂，按照质量比100:8，丁酸钠2000mg和烟酰胺80mg、烟酸80mg，混合均匀。按照现有微胶囊化的方法，将羟丙基甲基纤维素、壳聚糖和二氧化硅混合并在流化床中230℃高温沸腾膨胀，得到混合物，然后将丁酸、丁酸钠、烟酰胺和烟酸的水溶液喷涂到上述混合物上，高温干燥后低温固化，使组合物颗粒固化成型，然后将包膜材料巴西棕榈蜡、棕榈油脂和聚乙二醇溶于有机溶剂，在流化床中进行底喷包衣，得到包膜均匀的丁酸钠-烟酰胺-烟酸颗粒，组合物含量30%。
实施例5
一种保护仔猪肠道健康的添加剂，按照质量比100:6，丁酸1000mg、丁酸钾1000mg和烟酰胺120mg混合均匀。按照现有微胶囊化的方法，将羟丙基甲基纤维素、壳聚糖和二氧化硅混合并在流化床中230℃高温沸腾膨胀，得到混合物，然后将丁酸、丁酸钠、烟酰胺和烟酸的水溶液喷涂到上述混合物上，高温干燥后低温固化，使组合物颗粒固化成型，然后将包膜材料巴西棕榈蜡、棕榈油脂和聚乙二醇溶于有机溶剂，在流化床中进行底喷包衣，得到包膜均匀的丁酸-丁酸钾-烟酰胺颗粒，组合物含量40%。
应用例
试验选择72头健康状况良好、体重相近的断奶仔猪，随机分成6组，每组6重复，每重复2头仔猪。试验使用复合包被法，1-6组处理分别为，1组：基础日粮；2组：基础日粮+2%复合包被丁酸钠-烟酸（100:1）；3组：基础日粮+2%复合包被丁酸钠-烟酸（100:2）；4组：基础日粮+2%复合包被丁酸钠-烟酸（100:4）；5组：基础日粮+2%未包被丁酸钠和未包被烟酸（100:2）40mg/kg；6组：基础日粮+2%单独包被丁酸钠和包被烟酸（100:2），基础日粮按表1组成。
表1 基础日粮配方及营养组成
自由采食和饮水，试验第14天，称重，每组屠宰6头，采集血清、肝脏、大肠内容物以及各肠段组织等样品。生产性能如表2所示：
表2：日粮添加复合包被烟酸-丁酸对断奶仔猪生长性能的影响
（0-14d）
试验结果显示，饲料添加复合包被的烟酸-丁酸可以促进仔猪生长，当复合包被添加比例为100：2（试验3组）时效果最佳，且烟酸-丁酸复合包被添加的效果要优于单独包被添加的效果，若普通添加反而会抑制仔猪的生产性能、加剧腹泻。因此丁酸、烟酸的添加比例及其添加方法是其联合使用的关键。
对1、2、3、4组的粪便、结肠内容物样品进行16S生物信息分析，见图1。结果表明：试验3组中包被添加100：2的丁酸、烟酸，显示粪便中丁酸浓度显著升高（图1A）；结肠16S分析显示，随着丁酸、烟酸的添加，链杆菌的菌群相对丰度逐渐升高，但乳酸菌的菌群相对丰度逐渐下降，链杆菌、乳酸菌可通过代谢产生丁酸、烟酸（图1B）；粪便16S分析显示，随着丁酸、烟酸的添加，乳酸菌的菌群相对丰度逐渐升高（图1C）。以上说明该发明可改善仔猪肠道菌群及其代谢。
对1、2、3、4组的回肠组织样品的S100A8、TNF-α、IL-4等基因进行qPCR检测，见图2。结果显示包被添加烟酸和丁酸能有效抑制肠道炎症因子的表达，可调控肠道免疫功能。
Claims (4)
1.一种保护仔猪肠道健康的添加剂，所述添加剂为微胶囊包被的组合物，其特征在于组合物包含丁酸或/和丁酸盐与烟酸或/和烟酰胺。
2.根据权利要求1所述的一种保护仔猪肠道健康的添加剂，其特征在于微胶囊包被的组合物中丁酸或/和丁酸盐与烟酸或/和烟酰胺质量之比为100:1-100:8，且在微胶囊中的质量比为20%-40%。
3.根据权利要求1或2所述的一种保护仔猪肠道健康的添加剂，其特征在于微胶囊包被的组合物中丁酸盐中金属离子为锂、钠、钾。
4.根据权利要求1或2所述的一种保护仔猪肠道健康的添加剂使用方法，按照添加量0.5-3%添加到全价料使用。
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| CN114521617B (zh) * | 2022-03-21 | 2023-11-07 | 江苏农牧科技职业学院 | 预防猪腹泻的饲料添加剂及其制备方法 |
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