CN101351124B - 用于改变动物的肠道菌群的方法 - Google Patents
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Abstract
一种方法,通过对具有炎性肠病(IBD)或处于该疾病危险中的动物施用包括至少一种抗氧化剂的组合物,任选地结合益生菌和益生元中的一种或多种,从而增强该动物的胃肠道内的有益菌和有害菌之间的平衡。
Description
技术领域
本发明涉及改变动物,更具体而言是具有炎性肠病(IBD)或处于IBD危险中的动物的胃肠道(肠)的细菌群落,在一些情况中是减少胃肠炎症的方法。在某些实施方案中,这些方法包括饮食干预;因此本发明还涉及用于实施此类方法的食物组合物。本发明进一步还涉及用于实施本发明的试剂盒和传递工具。
背景技术
IBD与肠道菌群的变化有关;然而,正如Marteau et al.(2004),Aliment.Pharmacol.Ther.20(Suppl.4):18-23的评论论文中所总结的,这是一个棘手的课题,需要进行更多的研究。Marteau的论文中所总结的各种研究指出了通过施用益生菌(probiotic)来改变细菌群落对IBD的影响。
Kruis(2004),Aliment.Pharmacol.Ther.20(Suppl.4):75-78评论了益生菌对IBD的治疗效果的临床研究。据报道一些研究显示出了令人信服的治疗效果,而其他一些则没有。
在Jergens(1999),Veterinary Clinics of North America:SmallAnimal Practice 29(2):501-521的另一篇评论论文中,指出“目前缺乏菌群在犬科/猫科IBD中的作用的证据”。Jergens证明了用于IBD的饮食疗法,着眼于低变应原性饮食,调节omega-6与omega-3的脂肪酸比率和纤维补充物。
Fernandez-Banares et al.(1989),Amer.J.Gastroenterol.84(7):744-748报道患有IBD的人类患者具有比健康对照组更低的某些维生素(包括维生素C和β-胡萝卜素,但不包括维生素E)的血浆水平。
Buffinton&Doe(1995),Free Radical Biology&Medicine 19(6):911-918报道了具有IBD的患者中的降低的抗氧化防护,并注意到广泛用于IBD治疗的消炎药5-氨基水杨酸(5-ASA),例如以其前药柳氮磺吡啶的形式,具有较强的抗氧化能力。抗氧化治疗的初步试验被引证,据说其“鼓励了抗氧化策略对于IBD治疗的进一步探索”。
Lih-Brody et al.(1996),Digestive Diseases&Sciences 41(10):2078-2086报道了活性氧中间体(ROI)在IBD患者的结肠黏膜中的研究,并指出ROI的形成和抗氧化微量营养素的失衡“可能为使用抗氧化剂的治疗调节提供了理论依据”。
D’Odorico et al.(2001),Scand.J.Gastroenterol.36(12):1289-1294报道了与对照组相比IBD患者血浆中的抗氧化剂(包括维生素E和β-胡萝卜素)的浓度下降,并得出结论认为抗氧化剂的损耗在IBD的病理生理学上很可能是至关重要的。
González et al.(2001),Int.J.Vitam.Nutr.Res.71(4):243-250报道了在大鼠模型中增补维生素E可使结肠免受与炎症有关的氧化应激。
在本领域中仍然需要新方法以改变具有IBD或处于IBD危险中的动物的肠道菌群,尤其是调节肠道内有益菌和有害(例如,致病的)菌的平衡以有利于有益菌。
发明内容
现在提供了一种用于增强具有IBD或处于IBD危险中的动物的胃肠道内的有益菌和有害菌之间的平衡的方法,所述方法包括对该动物施用包括至少一种抗氧化剂例如维生素E、维生素C和/或类胡罗卜素的组合物。
在一些实施方案中,可归因于所述方法的增强与炎症的减少相关。
任选地,所述方法还包括对该动物施用益生菌(probiotic)和益生元(prebiotic)中的至少一种。
本发明还提供至少一种抗氧化剂在制备用于增强具有IBD或处于IBD危险中的动物的胃肠道内的有益菌和有害菌之间的平衡的组合物中的用途。
还提供一种食物组合物,以干物质为基础所述食物组合物包括下列物质中的至少一种:a.维生素E,其量为约50μg/g~约1000μg/g;b.维生素C,其量为约30μg/g~400μg/g;和c.β-胡萝卜素,其量为约0.1μg/g~约5μg/g;并且进一步包括益生菌和益生元中的至少一种。
进而还提供一种试剂盒,所述试剂盒包括(1)含有至少一种抗氧化剂的组合物,和(2)下列物质中的至少一种:a.益生菌;b.益生元;c.基础食物;d.抗IBD试剂;和e.说明书,用于对具有IBD或处于IBD危险中的动物施用所述的含抗氧化剂的组合物和任选的所述试剂盒的其他组分,以增强胃肠道内的有益菌和有害菌之间的平衡。
进而还提供一种工具,该工具用于传递关于以下各项中的一项或多项的信息和/或说明:a.对具有IBD或处于IBD危险中的动物施用包括至少一种抗氧化剂的组合物,任选地结合(i)益生菌、(ii)益生元和(iii)抗IBD试剂中的一种或多种,以增强该动物的胃肠道内的有益菌和有害菌之间的平衡;b.使包括至少一种抗氧化剂的组合物与(i)益生菌、(ii)益生元、(iii)抗IBD试剂和(iv)基础食物中的一种或多种混合,以向具有IBD或处于IBD危险中的动物提供组合施用,从而增强该动物的胃肠道内的有益菌和有害菌之间的平衡;并c.使用试剂盒以增强具有IBD或处于IBD危险中的动物的胃肠道内的有益菌和有害菌之间的平衡;其中,所述工具包括具有这些信息和/或说明的文献、数字存储介质、光学存贮介质、音频显示(audio presentation)和视觉显示器中的一种或多种。
具体实施方式
本发明的方法用于增强具有IBD或处于IBD危险中的动物胃肠道内的有益菌和有害菌之间的平衡。该方法包括对该动物施用包括至少一种抗氧化剂的组合物。
肠道菌群,即存在于胃肠道内的细菌群落,包括有益菌和有害菌的型或种。肠道菌群的具体成员在具体环境下对动物的健康是否是有益的、有害的还是不重要的取决于诸多因素,不过就本发明的目的而言,某些型或种的细菌可被认为是有益的,而其他则视为有害的。肠道菌群有益成员的实例包括双歧杆菌(bifidobacteria)(双歧杆菌属种)和乳酸菌,更具体而言是乳酸杆菌属种。有害菌包括致病菌。肠道菌群有害成员的实例包括梭状芽孢杆菌属(clostridium spp.)、脱硫弧菌属(desulfovibrio spp.)(包括但不限于去磺弧菌(D.desulfuricans)、D.intestinalis和普通脱硫弧菌(D.vulgaris))、螺杆菌属(Helicobacter spp.)(包括但不限于H.bizzozeronii、猫胃螺杆菌(H.felis)、海尔曼螺杆菌(H.heilmannii)、幽门螺杆菌(H.pylori)和H.salomonis)和致病型大肠杆菌((Escherichia coli))。
胃肠健康通常取决于有益菌和有害菌的适当平衡的维持。有害菌总数的增多和/或有益菌总数的减少与胃肠健康的下降相关。相反,有益菌总数的增多和/或有害菌总数的减少可能与胃肠健康的改善相关,所述改善例如具有胃肠失调如IBD的动物恢复健康或好转,或者预防存在该失调的危险的动物发病。本文中的术语“相关”并不一定意味着因果关系,因而有益菌和有害菌的平衡可隐含在发病机理中或仅仅是胃肠失调的症状。
平衡的“增强”或“增强作用”此处是指改变平衡以有利于有益菌,因此可包括增加有益菌和/或减少有害菌。在本发明的一些实施方案中,平衡的增强作用源自有害菌如致病菌的减少和有益菌的增多。
肠道菌群中的细菌总数可由本领域内任何公知的方法评估。例如,粪便样品可使用常规平皿培养法培养,或通过荧光原位杂交(FISH)技术例示。
根据本发明方法的受试动物是“具有IBD或处于IBD危险中的”动物。具有IBD的动物是这样的动物:其中被认为是IBD形式的一系列炎性胃肠疾病和失调中的任一种已得到确诊,或者表现出与该诊断相一致的症状。这样的疾病和失调包括而不限于过敏性肠综合征(IBS)、溃疡性结肠炎和克罗恩病。具有慢性IBD但在施用本方法时得到缓解的动物此处被视为“具有IBD”的动物。处于IBD危险中的动物是不具有IBD病史或未展现IBD症状但具有一个或一个以上显示对IBD发病具有易感性的致病因素的动物。这样的致病因素可包括遗传因素(例如IBD的家族史)和生理因素(例如一种或多种促炎性生物标志的升高的水平和/或一种或多种抗炎性生物标志降低的水平)。
所述动物可以是人类或非人类,包括鸟类、牛科、犬科、马科、猫科、山羊、鼠科、绵羊和猪科动物。在一些实施方案中,所述动物是伴侣动物,如犬科或猫科,特别是狗或猫。
根据本发明,对所述动物施用包括至少一种抗氧化剂的组合物。施用可通过任何适宜的途径进行,包括口服或非肠道施用,但通常为口服。在一些实施方案中,所述组合物是口服的食物。包括至少一种抗氧化剂的此类食物可代表动物饮食的实质部分。例如,至少一种抗氧化剂可存在于由动物日常食用的并基本上提供该动物的全部营养的一种食物或一系列食物中。作为选择或另外地,至少一种抗氧化剂可作为营养添加剂施用,或可以存在于与常规食物分开给予动物的小吃、零食(treat)或至少部分可食用的玩具中。
可以使用任何在营养上可接受的抗氧化剂。在一些实施方案中,使用不同于具有药理学性质的抗氧化剂(正如在诸如5-ASA等药物或其药物前体的情况中)的抗氧化剂。在一些实施方案中,使用不同于多酚的抗氧化剂,不过除了非多酚抗氧化剂之外诸如紫杉醇等多酚抗氧化剂可以任选存在。展现出游离基猝灭或吸收能力的各种物质可用作抗氧化剂(例如水果、蔬菜、某些维生素和其他的化合物)。具有很高的氧游离基吸收能力的粗组分包括例如生菠菜渣、生番茄渣、生粗柑桔浆、生葡萄渣、生胡萝卜粒、生花椰菜、绿毛茶、生玉米蛋白质和粗米糠。展现出自由基猝灭或吸收能力的食物或食物产品包括例如菠菜(如菠菜渣)、番茄(如番茄渣)、柑桔类水果(如柑桔浆)、葡萄(如葡萄渣)、胡萝卜(如胡萝卜粒)、椰菜、玉米蛋白质和米糠。展现出自由基猝灭或吸收能力的化合物包括例如维生E、维生素C、类胡萝卜素、辅酶Q10(辅酶Q)、谷胱甘肽、L-肉毒碱、α-硫辛酸、N-乙酰半胱氨酸、S-腺苷甲硫氨酸、大豆异黄酮和牛磺酸。
在一些实施方案中,待施用的组合物包括维生素E、维生素C和类胡萝卜素中的一种或多种。
术语“维生素E”此处包括适宜由动物食用的维生素E的任何形式,包括但不限于任何生育酚或生育三烯酚化合物、任何旋光对映异构体或其外消旋物,和具有维生素E活性的这类化合物的任何混合物,如α-生育酚(5,7,8-三甲基母育酚)、β-生育酚(5,8-二甲基母育酚)、γ-生育酚(7,8-二甲基母育酚)、δ-生育酚(8-甲基母育酚)、α-生育三烯酚(5,7,8-三甲基生育三烯酚)、β-生育三烯酚(5,8-二甲基生育三烯酚)、γ-生育三烯酚(7,8-二甲基生育三烯酚)和δ-生育三烯酚(8-甲基生育三烯酚)。维生素E可作为上述化合物的任一种或上述化合物的混合物施用,或以此类化合物的各种衍生物如酯类(包括维生素E的乙酸酯、琥珀酸酯、棕榈酸酯等)的形式施用,所述衍生物在被动物摄取后展现出维生素E活性。通常,用于本方法的维生素E包括α-生育酚或其酯。维生素E的量可以以国际单位(IU)表示,其中1IU是相当于1mgDL-α-生育酚醋酸酯的具有维生素E活性的维生素E的量。作为选择,维生素E的量也可以以总生育酚表示。
术语“维生素C”此处包括适宜由动物食用的维生素C的任何形式,包括但不限于抗坏血酸、L-抗坏血酸及其各种衍生物如磷酸钙盐、胆甾基盐和抗坏血酸盐-2-一磷酸盐。维生素C的盐包括钠盐、钙盐、锌盐和铁盐。酯包括硬脂酸酯、棕榈酸酯和类似衍生物。维生素C可以为被患者摄取后展现出维生素C活性的任何物质形态如液体、半固体、固体或热稳定形态。维生素C的量此处以抗坏血酸表示。
术语“类胡萝卜素”此处包括适宜由动物食用的类胡罗卜素的任何形式,包括但不限于来自植物、藻类、叶、根、植被、番茄粉、红色棕榈油、番茄粉和番茄渣/浆中的橙-黄色素的天然的和合成的类胡萝卜素。类胡萝卜素β-胡萝卜素是维生素A的前体,天然存在于植物中。类胡萝卜素的抗氧化活性通常与它们通过动物的新陈代谢而转化为维生素A所具有的任何维生素A的活性无关。在这点上,应当注意特别是猫通常不能将β-胡萝卜素转化为维生素A。其他的类胡萝卜素包括虾青素、α-胡罗卜素、玉米黄质、叶黄素、番茄红素和玉米黄质。
用于此处施用的一种或多种抗氧化剂的适宜的量可以相对于由动物所食用的食物量(通常以干物质为基础表示)表示。例如,含有抗氧化剂的组合物可以以占每克被食用食物的量(以干物质为基础)来提供一种或多种的下述物质:a.维生素E,总生育酚的量为约50μg~约1000μg,例如约100μg~约800μg,或约200μg~约600μg;b.维生素C,其量为约30μg~约400μg,例如约50μg~约200μg,或约75μg~约150μg;和c.类胡萝卜素,例如β-胡萝卜素,其量为约0.1μg~约5μg,例如约0.2μg~约2μg,或约0.5μg~约1.5μg。
根据本发明方法的待施用的组合物是构成动物的饮食的基本部分的食物时,所述食物通常应当包括一种或多种的下列物质(以干物质为基础):a.维生素E,总生育酚的量为约50μg/g~约1000μg/g,例如约100μg/g~约800μg/g,或约200μg/g~约600μg/g;b.维生素C,其量为约30μg/g~约400μg/g,例如约50μg/g~约200μg/g,或约75μg/g~约150μg/g;和c.类胡萝卜素,例如β-胡萝卜素,其量为约0.1μg/g~约5μg/g,例如约0.2μg/g~约2μg/g,或约0.5μg/g~约1.5μg/g。
在一个实施方案中,维生素E、维生素C和类胡萝卜素(例如β-胡萝卜素)这三种均以例如上述的量存在。
包括维生素E、维生素C和/或类胡萝卜素的组合物不同于构成动物的饮食的基本部分的食物时,它通常应当以与上文所列的量相一致的量(相对于由动物食用的食物的量)施用。通常,在添加剂、小吃、零食或至少部分可食用的玩具的情况中,由于食用的该组合物的总量大大低于构成饮食的基本部分的食物的情况,因此所述组合物包含比前述设定更高浓度的抗氧化剂。
根据本发明,令人惊讶的发现施用富含维生素E、维生素C和β-胡萝卜素的食物相比于具有较低水平的这些抗氧化剂的对照食物可增强动物肠道菌群中的有益菌和有害菌的平衡。在一些情况中,增强同时包括有益菌总数的增多和有害菌总数的减少。
在本发明的一些实施方案中,可归因于实施本方法的肠道菌群平衡的增强与炎症的减少,更特别是胃肠炎症(如结肠黏膜的炎症)的减少相关。炎症的减少可被直接观察到,例如通过结肠镜检查,也可以由动物的生物流体或组织中的一种或多种的促炎性生物标志的减少和/或一种或多种的抗炎性生物标志的增多证明。可在血清中减少的促炎性生物标志的实例包括C-反应蛋白(CRP)、氧化型谷胱甘肽(GSSG)、烯烃(alkenals)、血清淀粉状蛋白A(SAA)和肿瘤坏死因子α(TNF-α、促炎性细胞因子)。可在血清中增多的抗炎性生物标志包括还原型谷胱甘肽(GSH)、氧自由基吸收能力(ORAC)和抗炎性细胞因子转化生长因子β(TGF-β)和白细胞介素10(IL-10)。
任选地,本发明的方法除了施用包括抗氧化剂的组合物之外还包括施用益生菌和益生元中的一种或多种。
益生菌是包含活的微生物,如细菌、真菌或酵母的制剂或组合物。此处所关注的益生菌包括至少一种有益菌,例如双歧杆菌和/或乳酸菌。在一个实施方案中,此处有用的益生菌包括有益菌,所述有益菌包括一种或多种的双歧杆菌属和乳酸杆菌属。适宜的种包括但不限于动物双歧杆菌(bifidobacterium animalis)(包括B.animalis subsp.Lactis,有时称为乳酸双歧杆菌(B.lactis))、长双歧杆菌(bifidobacterium sanimalis)(包括婴儿双歧杆菌(B.infantis))、嗜热双歧杆菌(Bifidobacterium thermophilum)、嗜酸性乳酸菌(Lactobacillusacidophilus)、动物乳酸杆菌(Lactobacillus animalis)、干酪乳杆菌(Lactobacillus casei)、植物乳杆菌(Lactobacillus plantarum)、路氏乳杆菌(Lactobacillus reuteri)和鼠李糖乳杆菌(Lactobacillus rhamnosus)。
益生菌可以与抗氧化剂包含在同一组合物中,例如食物组合物中,或者也可以单独施用。益生菌的适宜的量通常占动物所食用的每克食物的约106cfu~约1012cfu(集落形成单位)(以干物质为基础)。
与抗氧化剂相结合,益生菌可仅通过用作有益菌总数增加的接种物和/或通过遏制有害菌的生长来增强肠道菌群的平衡。在一些情况中,可以发生抗氧化剂与益生菌的共同作用,由此在一些条件下导致抗氧化剂与益生菌的协同相互作用,但是这样的协同作用此处并非必须的。
益生元是优先刺激有益菌生长的不易消化的物质。绝大多数的益生元是发酵性碳水化合物;其实例包括寡糖、半乳聚糖和β-葡聚糖,可从各种植物和微生物来源获得。具体实例包括阿拉伯半乳聚糖、低聚果糖(FOS)和菊粉、产生FOS的多糖。益生元可以单独施用,或在与抗氧化剂相同的组合物,如食物组合物中施用。
在另一实施方案中,本发明的方法除了包括施用含有抗氧化剂(任选含有益生菌和/或益生元)的组合物外,还包括施用抗IBD试剂。此处的“抗IBD试剂”是药物试剂,通常是药品或中草药制剂,为IBD患者提供治疗效果,例如减少炎症、缓解诸如疼痛和/或腹泻等症状等等。适宜的实例包括但不限于类固醇如氯地米松、布地奈、波尼松龙、强的松和替可的松;5-ASA释放制剂如美沙拉嗪、奥沙拉嗪和柳氮磺吡啶;甲硝唑;硫唑嘌呤;等等。抗IBD试剂可通过任何适宜的途径施用,包括口服途径、非肠道途径、经皮途径和直肠途径。需要时,适于口服施用的抗IBD试剂可与抗氧化剂包含在同一组合物中。
此外,本发明的一个方面是至少一种抗氧化剂在制备用于增强具有IBD或处于IBD危险中的动物的胃肠道内的有益菌和有害菌之间的平衡的组合物中的用途。对于本发明的方法而言,以上描述或列举的全部实施方案同等地适用该用途。
本发明在又一实施方案中提供可用于例如实施此处描述的方法的一种食物组合物。本实施方案的食物组合物通常具有一定量的代谢能和营养物,这使其适宜用作动物饮食的基本部分。所述组合物以干物质为基础包括(1)下列物质中的至少一种:a.维生素E,总生育酚的量为约50μg/g~约1000μg/g,例如约100μg/g~约800μg/g,或约200μg/g~约600μg/g;b.维生素C,其量为约30μg/g~约400μg/g,例如约50μg/g~约200μg/g,或约75μg/g~约150μg/g;和c.类胡萝卜素,例如β-胡萝卜素,其量为约0.1μg/g~约5μg/g,例如约0.2μg/g~约2μg/g,或约0.5μg/g~约1.5μg/g;和(2)益生菌和益生元中的至少一种。
在描述性的实施方案中,所述组合物包含益生菌,所述益生菌包括双歧杆菌属和乳酸杆菌属中的一种或多种的有益菌。益生菌的适宜的量以干物质为基础通常为约106cfu~约1012cfu/g。
在另一个描述性实施方案中,所述组合物包含益生元,所述益生元包括寡糖、半乳聚糖或β-葡聚糖中的一种或多种。
食物组合物通常含有对于意欲喂食的动物来说适当的营养物的量和平衡。在一个实施方案中,所述组合物是宠物食品,例如营养上和/或明显适于喂养伴侣动物如犬科动物或猫科动物的食品。
本发明的试剂盒包括(1)包含至少一种抗氧化剂的组合物,和(2)下列物质中的至少一种:a.益生菌;b.益生元;c.基础食物;d.抗IBD试剂;和e.说明书,用于对具有IBD或处于IBD危险中的动物施用所述的含抗氧化剂的组合物和任选的所述试剂盒的其他组分,以增强胃肠道内的有益菌和有害菌之间的平衡。
试剂盒的各组分可以共同包装在一起,例如提供在单一外包装内的各单独的容器里或者以其他方式堆放在一起。作为选择,试剂盒的各组分也可以分别包装但以消费者可获得全部必要组分的方式提供(例如销售、表示出价或出售)。这可以通过例如“虚拟包装”实现,其中与试剂盒的物质组分分开的介质中的说明书涉及试剂盒中物质组分的应用。说明书用介质可以是但不限于例如在销售点的印刷品、广播或电视广播、网站或视觉显示器。
在一个实施方案中,所述试剂盒包括基础食物、含有至少一种抗氧化剂的组合物、以及益生菌和益生元中的一种或多种。基础食物具有对于意欲喂食的动物来说适当的营养物的量和平衡,但含有少量的抗氧化剂,通常不足以对胃肠道内有益菌和有害菌的平衡提供增强作用。含有抗氧化剂的组合物用作添加剂,添加至基础食物中或与基础食物混合,以提供富含抗氧化剂、能提供所需增强作用的食物。益生菌和/或益生元如果包括在试剂盒内则可以存在于添加剂中,或在基础食物中,或在单独的容器中。该实施方案的试剂盒任选地还包括将添加剂添加或混合至基础食物的说明书和/或关于该添加或混合的效果的信息。
在再一个实施方案中,提供了一种用于传递关于以下各项中的一项或多项的信息和/或说明的工具:a.对具有IBD或处于IBD危险中的动物施用包括至少一种抗氧化剂的组合物,任选结合(i)益生菌、(ii)益生元和(iii)抗IBD试剂中的一种或多种,以增强该动物的胃肠道内的有益菌和有害菌之间的平衡;b.使包括至少一种抗氧化剂的组合物与(i)益生菌、(ii)益生元、(iii)抗IBD试剂和(iv)基础食物中的一种或多种混合,以向具有IBD或处于IBD危险中的动物提供组合施用,从而增强该动物的胃肠道内的有益菌和有害菌之间的平衡;并c.使用本发明的试剂盒以增强具有IBD或处于IBD危险中的动物的胃肠道内的有益菌和有害菌之间的平衡;其中,所述工具包括具有这些信息和/或说明书的文献、数字存储介质、光存贮介质、音频显示和视觉显示器中的一种或多种。举例来说,所述工具包括显示网址、手册、产品标签、包装说明书、广告或视觉显示器。
本发明并不限于此处描述的具体方法、方案和试剂,因为它们可以变化。此外,此处使用的术语仅是用于描述具体实施方案,无意于限制本发明的范围。正如在此处和所附权利要求中所用的,单数形式a”、“an”和“the”包括复数含义,除非文中另有清晰所指。同样,单词“comprise(包括)”、“comprises”和“comprising”被解释为具有包括性,而非排他性。
除非另作说明,此处使用的全部科技术语以及任何缩写具有与本发明的领域中的普通技术人员通常所理解的相同的含义。尽管在实施本发明时可以使用与此处描述的那些类似的或相同的任何方法和材料,不过此处描述的方法、装置和材料是优选的。
在法律允许的条件下,此处提及的所有专利、专利申请和出版物此处通过引用的方式引入本文,用于描述和公开这些文献中所公开的、可能同本发明一起使用的化合物、方法、技术、步骤、技术、物品和其他组合物和方法。然而,此处所提及的任一项不应当被理解为一种许可,即,本发明未被授权以居先于利用在先发明的该公开。
实施例
本发明通过其优选实施方案的下列实施例可被进一步描述,不过应当理解这些实施例仅是用于描述的目的,其意图不在于限制本发明的范围,除非另作具体说明。
实施例1
使用11只健康猫(不具有IBD)和11只被诊断具有IBD的猫进行研究。用富含抗氧化剂或不含抗氧化剂的标准罐装猫科动物宠物食品(参见表1中的分析)喂养所述猫2周,随后换为另一种食品,再喂养2周。表1不含(对照)和富含(测试)食品的分析(DM=干物质)
对照食物 | 测试食物 | |
水分(%) | 75 | 74 |
蛋白质(%) | 9 | 9 |
脂肪(%) | 8 | 8 |
碳水化合物(%) | 6 | 7 |
粗纤维(%) | 0.2 | 0.2 |
总生育酚(μg/g DM) | 79 | 221 |
维生素C(μg/g DM) | 34 | 87 |
β-胡萝卜素(μg/g DM) | 0.05 | 0.92 |
在每个2周喂养期结束时,采集每只猫的血样。测定作为抗氧化剂生物标志的还原型和氧化型谷胱甘肽(分别为GSH和GSSG)的血清水平。平均水平显示在表2中。此外,响应于非特异性有丝分裂原伴刀豆球蛋白A(ConA)和美洲商陆有丝分裂原(PWM)的T淋巴细胞增殖水平被测定作为炎症反应的生物标志。平均响应水平显示在表3中。表2使用对照食品和测试食品的猫血清中的GSH和GSSG水平表3响应于有丝分裂原ConA和PWM的T淋巴细胞增殖
如表2所示,给食富含抗氧化剂的食物在健康猫和患有IBD的猫中均得到较高的GSH水平。给食对照(不富含)食物时,患有IBD的猫的GSH水平低于健康猫的该水平;给食富含抗氧化剂的食物将患有IBD的猫的GSH水平提高至与给食对照食物的健康猫的水平相当的水平。
如表3所示,用富含抗氧化剂的食物喂养患有IBD的猫使得T淋巴细胞增殖响应接近在健康猫中所观察到的水平。不过,该响应未完全正常化(未等同于健康猫的该响应)。
实施例2
使用11只健康猫和11只被诊断具有IBD的猫进行研究。以与实施例1中相同的对照(不富含)食物和测试(富含抗氧化剂)食物中的每一种喂养所述猫4周,随后换成另一种食物,再喂养4周。在每个4周喂养期的开始和结束时收集粪便(排泄物)样品,并使用常规平皿培养法对该样品进行细菌培养。获得两种有害菌(梭状芽孢杆菌(clostridia)和大肠杆菌(E.coli))和两种有益菌(乳酸菌(lactic acidbacteria)和双歧杆菌(bifidobacteria))的计数。结果显示在表4中。表4利用常规平皿培养法的粪便对数值cfu/g
如表4所示,来自患有IBD的猫的样品中的大肠杆菌总数比来自健康猫的样品中的大肠杆菌总数高约3个对数单位(约1000倍)。给食富含抗氧化剂食物的猫与给食对照食物的猫相比显示出大肠杆菌总数下降约0.8个对数单位~约1个对数单位。富含抗氧化剂的食物也倾向于减少梭状芽孢杆菌总数,不过该效果在健康猫中比在患有IBD的猫中更显著。同时,用富含抗氧化剂食物喂养的患有IBD的猫与用对照食物喂养的这些猫相比有益菌(乳酸菌和双歧杆菌两者)的总数增多。在该项研究中,健康猫中仅有双歧杆菌针对富含抗氧化剂的食物显示出增多。
从该项研究中可以得出对具有IBD的动物施用富含抗氧化剂的饮食增强了肠道菌群中有益菌和有害菌的平衡。这种增强作用可通过例如将一种或多种益生菌(包括诸如乳酸菌属或双歧杆菌属等有益菌)添加到富含抗氧化剂的食物中得到进一步协助。
在本说明书中,已经公开了本发明的典型的优选实施方案,尽管采用了具体概念,不过它们仅以一般性和描述性意义使用,而非用于限制,本发明的范围由权利要求阐明。显然,根据上述教导可以对本发明进行许多改进和变化。因而可以理解,除非另作具体说明,在所附权利要求的范围内可以实施本发明。
Claims (23)
1. 至少一种选自维生素E、维生素C和β-胡萝卜素的抗氧化剂作为唯一活性成份在制备用于增强具有炎性肠病(IBD)或处于该疾病危险中的动物的胃肠道内的有益菌和有害菌之间的平衡的组合物中的用途。
2. 如权利要求1所述的用途,其中所述增强包括有益菌水平的增大和有害菌水平的降低。
3. 如权利要求2所述的用途,其中所述有益菌包括乳酸杆菌属(Lactobacillus spp.)和双歧杆菌属(Bifidobacterium spp.)中的一种或多种。
4. 如权利要求2所述的用途,其中所述有害菌包括梭状芽孢杆菌属(Clostridium spp.)、脱硫弧菌属(Desulfovibrio spp.)、螺杆菌属(Helicobacter spp.)和致病型大肠杆菌(Escherichia coli)中的一种或多种。
5. 如权利要求1所述的用途,其中所述增强与炎症的减少相关。
6. 如权利要求5所述的用途,其中所述炎症的减少由所述动物的生物流体或组织中的促炎性生物标志的减少和/或抗炎性生物标志的增多证明。
7. 如权利要求6所述的用途,其中血清CRP、氧化型谷胱甘肽、烯烃、淀粉状蛋白和TNF-α中的至少一种减少和/或血清还原型谷胱甘肽、ORAC、TGF-β和IL-10中的至少一种增多。
8. 如权利要求1所述的用途,其中所述组合物以提供至少一种下述物质的量被施用:
a. 维生素E,总生育酚的量为50 μg~1000 μg;
b. 维生素C,其量为30 μg~400 μg;和
c. β-胡萝卜素,其量为0.1 μg~5 μg;
以每克由所述动物食用的以干物质为基础的食物计。
9. 如权利要求1所述的用途,其中所述组合物以提供至少一种下述物质的量被施用:
a. 维生素E,总生育酚的量为100 μg~800 μg;
b. 维生素C,其量为50 μg~200 μg;和
c. β-胡萝卜素,其量为0.2 μg~2 μg;
以每克由所述动物食用的以干物质为基础的食物计。
10. 如权利要求1所述的用途,其中所述组合物是食物、添加剂、或至少部分可食用的玩具。
11. 如权利要求1所述的用途,其中所述组合物是小吃或零食。
12. 如权利要求1所述的用途,其中所述组合物是作为所述动物的饮食的一部分被口服施用的食物。
13. 如权利要求12所述的用途,其中以干物质为基础所述食物包括下列物质中的至少一种:
a. 维生素E,总生育酚的量为50 μg/g~1000 μg/g;
b. 维生素C,其量为30 μg/g~400 μg/g;和
c. β-胡萝卜素,其量为0.1 μg/g~5 μg/g。
14. 如权利要求12所述的用途,其中以干物质为基础所述食物包括下列物质中的至少一种:
a. 维生素E,总生育酚的量为100 μg/g~800 μg/g;
b. 维生素C,其量为50 μg/g~200 μg/g;和
c. β-胡萝卜素,其量为0.2 μg/g~2 μg/g。
15. 如权利要求1所述的用途,其中所述组合物结合一种或多种抗IBD试剂的施用而被施用。
16. 如权利要求1所述的用途,其中所述动物是犬科动物或猫科动物。
17. 一种用于增强具有炎性肠病(IBD)或处于该疾病危险中的动物的胃肠道内的有益菌和有害菌之间的平衡的食物组合物,以干物质为基础,所述组合物的活性成份由下列物质中的至少一种组成:
a. 维生素E,总生育酚的量为50 μg/g~1000 μg/g,
b. 维生素C,其量为30 μg/g~400 μg/g,和
c. β-胡萝卜素,其量为0.1 μg/g~5 μg/g。
18. 如权利要求17所述的组合物,以干物质为基础,所述组合物的活性成份由下列物质中的至少一种组成:
a. 维生素E,总生育酚的量为100 μg/g~800 μg/g;
b. 维生素C,其量为50 μg/g~200 μg/g;和
c. β-胡萝卜素,其量为0.2 μg/g~2 μg/g。
19. 如权利要求17所述的组合物,所述组合物还包括益生菌,所述益生菌包括含双歧杆菌属(Bifidobacterium spp.)和乳酸杆菌属(Lactobacillus spp.)中的一种或多种的有益菌。
20. 如权利要求19所述的组合物,以干物质为基础,所述组合物包括106 cfu/g~1012 cfu/g的益生菌。
21. 如权利要求17所述的组合物,所述组合物还包括包含寡糖、半乳聚糖或β-葡聚糖中的一种或多种的益生元。
22. 如权利要求17所述的组合物,所述组合物是犬科的或猫科的宠物食品。
23. 一种试剂盒,所述试剂盒包括(1)权利要求17的组合物,和(2)下列项目中的至少一种:
a. 益生菌;
b. 益生元;
c. 基础食物;
d. 抗IBD试剂;和
e. 说明书,用于对具有IBD或处于IBD危险中的动物施用所述试剂盒的含抗氧化剂的组合物和任选的其他组分,以增强胃肠道内的有益菌和有害菌之间的平衡。
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ATE541469T1 (de) | 2012-02-15 |
DK1978821T3 (da) | 2012-05-14 |
ES2379824T3 (es) | 2012-05-04 |
BRPI0620734A2 (pt) | 2012-09-18 |
US20070178078A1 (en) | 2007-08-02 |
JP2009522311A (ja) | 2009-06-11 |
EP1978821B2 (en) | 2019-02-06 |
RU2426451C2 (ru) | 2011-08-20 |
EP1978821A1 (en) | 2008-10-15 |
ZA200805413B (en) | 2013-03-27 |
CN101351124A (zh) | 2009-01-21 |
AU2006330421B2 (en) | 2011-03-24 |
AU2006330421A1 (en) | 2007-07-05 |
CA2635038A1 (en) | 2007-07-05 |
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