在全球经济及疫情等多重因素的影响下,消费者对功能性食品的需求持续增长,呈现稳健态势。功能性食品的概念最初由日本科学家首次提出[1],近年来,被公认为是能够在健康促进、福祉维持和疾病预防方面提供诸多益处的食品。数据显示,2022年中国功能性食品市场规模超过2 000亿元,2025年预计将以7.8%的复合年增长率增长至2 857亿元人民币。基于上述情况,国家对功能性食品的研究与开发日益加强关注。乳制品是目前用于功能性目的的食品之一,它是天然的健康产品,含有均衡饮食的重要作用,迄今为止,一直是功能性食品发展的主流。随着技术的发展及消费者需求的不断提高,“功能性乳制品”逐渐引起消费者的关注。功能性乳制品是在乳制品基础之上,精确添加一些功能成分或特殊营养物质而制得的乳制品[2]。通过对其整体营养成分比例进行合理的调整,以达到便于人体吸收利用、提升产品整体可接受性的目的。同时,可根据特定人群的营养健康需求,开发具有多种特定生理功能的乳制品。据报道,添加的功能成分或特殊营养物质主要包括了益生菌、益生元、矿物质、维生素、酶制剂等[3]。功能性乳制品不仅富含一般乳制品所固有的营养成分,还具备对人体健康的显著益处,这些益处包括抗氧化[4]、抗高血压[5]、免疫调节[6]、抗糖尿病[7]乃至骨骼保护[8]等多重功效,展现出巨大的发展潜力。基于此,本文主要针对功能性乳制品的分类(益生菌、益生元、维生素和矿物质、酶制剂,见图1),功能特性(调节肠道健康、提高认知能力、改善肥胖、降低糖尿病和心血管疾病风险、维持骨骼及口腔健康等)及其发挥重要功效的潜在机制进行简要概述,为功能性乳制品的未来开发提供有益参考。
图1 功能性乳制品的分类
Fig.1 Classification of functional dairy products
1 功能性乳制品种类
1.1 添加益生菌开发功能性乳制品
目前,添加益生菌已成为开发功能性乳制品的广受认可的途径之一。益生菌被定义为一类活的微生物,当摄入足够量时,能够为宿主带来健康益处[9]。乳制品被认为是益生菌的理想载体,其有助于益生菌在胃肠道中的定植。常见的发酵乳制品(如酸奶、奶酪、发酵酪乳、乳酸菌饮料、开菲尔酸奶酒、酸奶油、乳酒等)是将益生菌应用到乳制品的实例。发酵乳制品是指由乳酸菌发酵或乳酸菌与酵母菌共同发酵,在特定微生物作用下,将原料乳制成的一种酸性乳制品。这个发酵过程可以改变原料的酶活性和微生物的代谢活性,从而影响食品基质的营养和生物活性特性,对人类健康产生有益的影响。许多科学研究证实,发酵乳制品具有抗高血压、增强全身免疫力、降低胆固醇和血压的作用。它们还可以充当通过蛋白水解培养物发酵释放的生物活性肽的丰富来源,从而对内分泌、消化、心血管以及免疫和神经系统产生许多潜在健康益处[10]。近年来,科研工作者不断挖掘添加益生菌开发的功能性乳制品对人体健康的益处(图2)。AGRAWAL等[11]将乳双歧杆菌DN-173 010添加到牛乳中开发了一款酸奶,并且对酸奶的功能特性进行了研究,结果发现,与非发酵奶制品相比,食用发酵酸奶的患者胃胀减轻,结肠运输加速,症状得以缓解。此外,含有活性培养物的酸奶或开菲尔可显著增强乳糖消化并减少乳糖消化不良者的不耐受症状[12]。另一项临床试验证明,乳糖不耐受个体在食用了益生菌发酵的酸奶后其小肠中的乳糖酶活性显著增加,极大程度降低了胃肠疾病的风险[13]。奶酪的致密结构可以保护细菌免受胃肠道酸性环境的影响,因此被认为是将益生菌转移到胃肠道的重要基质。HU等[14]全面评估了利用益生菌开发的功能性乳制品-奶酪摄入量与心血管疾病以及心血管生物标志物之间的因果关系,结果显示奶酪摄入量与2型糖尿病、心力衰竭、冠心病、高血压和中风呈极显著负相关。此外,发酵乳制品可能激活一系列与调节和激活免疫细胞相关的基因进而发挥免疫作用。MERENSTEIN等[15]报告说,补充含双歧杆菌酸奶30 d增加了乳糖代谢和合成氨基酸的能力,同时降低了脂多糖合成的可能性,且与对照组相比,转录因子GATA3(一种参与早期分化和T 细胞谱系定型的转录因子)、CD80(一种与抗原识别相关的跨膜受体)、CXCL10(一种激活和吸引特定免疫细胞的趋化因子)的水平在食用双歧杆菌酸奶的成人血细胞中至少上调了5倍。一项人群干预研究的结果表明,食用发酵乳(400 g/d)2周可以改变肠道微生物群的种类及其代谢物,进而改善肠道屏障功能[16]。
图2 添加益生菌开发的功能性食品对 人体健康的益处[17]
Fig.2 Functional foods developed by adding probiotics on human health benefits
1.2 添加益生元开发功能性乳制品
益生元(包括乳果糖、低聚半乳糖、低聚果糖以及菊粉等)除了能够提升产品的感官特征外,还具备调节肠道微生物以及肠道环境的潜能。此外,益生元在发酵过程中产生的短链脂肪酸(short-chain fatty acids, SCFAs)能够促使大肠内调节性T细胞的增殖,扩展大肠上皮细胞的表面积,并提高钙、镁等矿物质元素的吸收能力[18-19]。因此,利用益生元开发功能性乳制品从而达到改善人体健康的目的是十分必要的。有研究指出,在酸奶制作中添加菊粉能够有效保护嗜热链球菌、乳杆菌或双歧杆菌等益生菌,同时在酸奶储存过程中减缓活菌数的下降、提升黏度、降低酸度以及乳清析出率,从而提升发酵乳的品质[20]。BURITI等[21]利用体外消化模拟试验研究了菊粉对益生菌-嗜酸乳杆菌的保护机制,发现菊粉对嗜酸乳杆菌有显著的保护效应。这种效应一方面可能归因于菊粉加强了嗜酸乳杆菌对不良环境的耐受性,另一方面,则可能源于菊粉所形成的微囊结构直接对益生菌发挥了保护作用。TIWARI等[22]研究了不同水平的菊粉作为脂肪替代品对冰淇淋品质的影响,并将实验冰淇淋与含有10%(质量分数)乳脂的冰淇淋(对照)进行比较,结果显示用2%和4%菊粉(均为质量分数)替代制备的冰淇淋的总体可接受性与对照相似。ÖZER等[23]研究了补充乳果糖和菊粉作为益生元对嗜酸乳杆菌和双歧杆菌在嗜酸乳杆菌酸奶中生长的影响,结果发现菊粉和乳果糖在有效促使了双歧杆菌的生长。ZIELI
SKA等[24]进行了一项研究,评估了在发酵乳中添加果糖和低聚果糖(1%和2%均为质量分数)对产品的物理化学、流变性、感官以及微生物质量的影响。结果发现,与未添加糖类的对照发酵乳制品相比,低聚果糖和果糖会导致细菌数量增加,且不同发酵乳样品的酸化程度以及黏度、坚固度、凝固性和颜色属性在贮藏期间都发生了变化。其中,添加了低聚果糖的样品在总体感官评分方面表现最为优异。植物甾醇通常指的是植物固醇,它们广泛存在于各种水果、蔬菜等植物的细胞膜中。这些植物甾醇不仅具备较高的营养价值,还具有降低血液胆固醇、抑制乳腺增生以及调节免疫的作用。国家和国际指南推荐添加植物甾醇和甾烷醇的功能性食品可作为促进心血管健康的饮食预防策略的重要选择,特别是针对高胆固醇的治疗。PARRAGA MART
NEZ等[25]评估了每天摄入 2 g植物甾醇(为期12 个月)对人体健康状况的影响,结果发现低密度脂蛋白(low density lipoprotein, LDL)胆固醇水平降低了11%,这对预防高脂血症和动脉硬化有良好作用。因此可将植物甾醇和甾烷醇添加到乳制品中来开发新型的功能性乳制品,从而增加消费者的选择。
1.3 添加维生素、矿物质开发功能性乳制品
近年来,在乳制品中添加维生素和矿物质进而开发功能性乳制品已被广泛研究。在生产中通常将含Ca、Fe、Zn等矿物元素或维生素(维生素A、维生素C、维生素D等)的配料制剂加入到原料乳中,经过一定的工艺流程制成含相应成分的功能性乳制品。如铁强化乳已被开发用于解决贫血问题,有效缓解了幼儿和学龄前儿童微量营养素缺乏的现状[26]。富硒乳可用于改善人体硒状态,同时降低患癌症的风险[27]。维生素D是一种必需的脂溶性维生素,对人体健康至关重要。目前,世界上越来越多的国家开始在乳制品中强化维生素D,美国的乳制品公司在20世纪30年代初便在牛乳中添加维生素D,从而达到预防儿童佝偻病的目的。TIPPETTS等[28]和GANESAN等[29]均利用维生素D强化奶酪,以实现奶酪最大强度的营养价值。LI等[30]在妊娠期糖尿病女性食用的原味酸奶中强化了 维生素D3(500 IU),干预16 周后发现LDL显著降低。相同的结果也被TOXQUI等[31]报道,他们在乳制品(500 mL)中加入了 15 mg Fe和200 UI(5 μg)维生素D3。
1.4 添加酶制剂开发功能性乳制品
酶通常是存在于所有具有生物催化活性的生物体内的蛋白质。在实际加工生产中,酶的作用是精确的,每种酶旨在启动具有特定结果的特定反应。截至目前,在乳制品技术中,涵盖酯酶、乳糖酶、脂肪酶、蛋白酶以及过氧化氢酶等的酶制剂被广泛应用。蛋白酶不仅可加速奶酪老化,作为一种具有功能特性的酶,它还可以降低婴儿对乳制品的过敏反应[32]。脂肪酶则主要用于奶酪的成熟过程,以改善其风味。对于乳糖不耐症患者而言,由于小肠中产生的乳糖酶相对较少,乳糖酶可将乳糖转化为半乳糖和葡萄糖,从而减缓牛奶给人体消化带来的不适症状(如痉挛和胀气)[33]。据研究,使用谷氨酰胺转氨酶(TGase)在改善由山羊奶制成的酸奶的功能特性方面效果显著,这体现在酸奶的凝胶稠度提高,乳清分离减少。
2 功能性乳制品的功效及其机制
近年来,功能性乳制品已被报道在调节肠道健康、提高认知能力、改善肥胖、降低糖尿病和心血管疾病、维持骨骼及口腔健康等方面效果显著。接下来,本文针对功能性乳制品的功效及其机制进行深入探讨。
2.1 调节肠道健康
肠道微生物被誉为人体的“第二大代谢器官” ,在维护人体健康方面承担着重要角色。它可参与调节人体的基本代谢途径,其失调会严重影响健康并造成疾病的困扰[34]。近年来,对于肠道菌群在人体健康中的作用机制不断被挖掘,涌现出“肠-肌轴”,“肠-脂轴”,“肠-脑轴”等多种理论体系[35]。因此,维持人体肠道微生物的平衡对宿主的健康至关重要。在此背景下,表1呈现了与功能性乳制品有关的调节肠道健康的相关研究成果。OKONIEWSKI等[36]综述了发酵乳制品对肠道菌群组成的作用。此外,FERNANDEZ-RAUDALES等[37]比较了日常饮食中牛奶与2种类型的豆浆(低甘氨酸豆浆和传统豆浆)对肥胖参与者肠道微生物群组成的影响,结果表明,在干预结束时,与食用豆浆的肥胖参与者相比,食用牛奶的肥胖参与者肠道中的乳酸杆菌显著增加,厚壁菌与拟杆菌的比例保持不变,而普雷沃氏菌的数量则呈下降趋势。YILMAZ等[38]进行的随机对照试验研究了开菲尔酸奶对炎症性肠病患者肠道微生物群的影响,发现每天食用400 mL开菲尔酸奶可显著提高乳杆菌的丰度。MERENSTEIN等[15]进行了一项为期30 d的实验,旨在探究含有BB-12的酸奶对人体肠道健康的影响,志愿者每天食用含动物双歧杆菌乳酸亚种BB-12的酸奶125 mL(早晚各一次),对照组食用不含BB-12的酸奶(对照组),试验期结束后肠道微生物结果显示潜在有益细菌在实验组显著增加,特别是双歧杆菌属,提高了代谢乳糖和合成氨基酸的能力,同时降低了脂多糖合成的潜力。此外,食用含有BB-12的酸奶会激活一系列与调节和激活免疫细胞相关的免疫基因。
表1 功能性乳制品对肠道健康的影响
Table 1 Effects of functional dairy products on intestinal health
功能性乳制品研究对象影响参考文献酸奶小鼠改善菌群失调引起的临床症状(食欲不振、便秘、胀气)[39]养乐多(添加干酪乳杆菌代田株)成年便秘患者改善便秘受试者的便秘相关症状及肠道微生物[40]酸奶(添加鼠李糖乳杆菌GG)儿童改善儿童急性腹泻[41]山羊奶粉和牛奶粉(添加菊粉和低聚果糖)大鼠改善大鼠肠道微生物区系(大肠中双歧杆菌的数量增加),并增加代谢产物(短链脂肪酸和有机酸)的产生[42]婴儿配方奶粉(添加低聚果糖)婴儿促进有益肠道微生物生长,抑制病原微生物[43]
2.2 提高认知能力
阿尔茨海默病是一种潜在起病隐秘、逐渐恶化的神经退行性疾病,其前驱征兆之一便是认知能力下降。鉴于目前尚缺乏针对阿尔茨海默病的有效治疗方法,因此有必要制定预防或减缓认知能力下降发展的策略。研究表明,认知功能在一定程度上可以通过饮食进行调节[44],并且通过采取适当的饮食和生活方式可以减缓认知功能的衰退[45]。BIRNIE等[46]前瞻性地分析了婴儿期的牛奶摄入量与认知功能的关联程度。该试验以1930年代参与过调查研究的儿童为试验对象,65年后通过评估405名老年参与者的步行能力判断牛奶对人认知功能的影响。数据显示,在儿童时期每天至少喝1杯牛奶的人其行走速度和平衡性更好(+5%)。此外,在认知发展/表现方面,RAHMANI等[47]在469名学生中也观察到了牛奶对认知和学习成绩的有利影响,这些学生每天摄入250 mL牛奶,并持续了3个月。研究已经证明,乳制品中发现的营养素可能对认知功能直接或间接产生有益影响,包括乳清蛋白、生物活性肽、α-乳清蛋白、维生素B12和钙[48],此外发酵乳制品中所含益生菌调节肠道微生物群的作用也可能影响认知功能[49]。RAHMAN等[50]的研究结果显示,奶酪消费者的信息处理及故事回忆得分更高。一项随机、双盲、对照试验评估了食用发酵乳与益生菌混合物12周对60名阿尔茨海默病患者认知功能的影响,结果显示,与食用牛奶的对照组相比,接受益生菌治疗的患者在简易智力状态检查量表(mini-mental state examination,MMSE)评分方面出现显著改善[51]。然而截止到目前,关于解释功能性乳制品与认知表现之间潜在机制的研究相对较少。目前的数据表明肠道微生物群在中枢神经系统中起着重要作用(图3),称为“肠脑轴”[52],更具体地说,临床研究表明,益生菌可减弱促炎细胞因子,减少氧化应激,增加脑源性神经营养因子,因此可促进神经元生长和存活[53]。此外,益生菌的代谢产物如色氨酸可作为信号分子刺激大脑中血清素的合成,进而提高认知能力[54]。总体而言,功能性乳制品介导认知功能的机制还有待深入研究。
2.3 改善肥胖
全球肥胖和超重率正在上升,这对全球的个人和医疗保健构成了重大的挑战。实际上,大量科研工作者致力于功能性乳制品改善人体肥胖方面的研究。大量研究表明,肠道微生物群是代谢综合征和肥胖的重要决定因素之一。因此饮食干预有望成为操控肠道微生物群进而预防和治疗代谢综合征和肥胖症的策略。某些乳制品(如酸奶)可能会通过调节肠道微生物群的组成从而操控代谢活动介导的抗肥胖作用[56-57]。FATHI等[58]观察到开菲尔或牛奶可以改善身体成分并减轻体重。WANG等[59]开展了一项3 440的人群实验,发现酸奶消费量高的人与消费量低的人相比,体重增加幅度要小50%以上(P=0.03)。在一项为期12周的安慰剂对照双盲研究中[60],125名超重/肥胖的成年人被随机分为以下4组接受不同热量零食棒的摄取:(1)对照;(2)菊粉型果聚糖(inulin-typefructan,ITF);(3)乳清蛋白;(4)ITF+乳清蛋白,随后,研究评估了食欲、身体成分的变化情况。结果显示,在12周时,与对照组相比,乳清蛋白组的体脂显著减少。此外,ITF、乳清蛋白和ITF +乳清蛋白的饥饿感、进食欲望和预期食物消费量均较低。近几年,已经发表了关于功能性乳制品改善肥胖潜在影响及其机制的研究。其中最常引用的机制与细胞内钙对脂肪细胞代谢的影响有关[61]。根据这一理论,膳食钙的增加通过对循环钙化激素的影响(抑制1, 25-羟基维生素D和甲状旁腺激素浓度)进而降低脂肪细胞中细胞内离子钙的浓度,这将抑制脂肪的从头合成[62]。还有一些证据表明,乳制品中的钙比钙补充剂发挥的作用更大,这可能是由于钙与乳制品中存在的几种生物活性化合物(例如支链氨基酸,即亮氨酸)协同作用[63-64]。此外,乳制品蛋白特别是乳清蛋白被认为是改善肥胖的有效物质[65-66]。乳清蛋白中的肽抑制血管紧张素转换酶被证实具有抑制血管紧张素II激素产生的能力,从而减少了脂肪细胞的生成和脂肪堆积[67-68]。同时,乳制品中的脂肪酸,如中链脂肪酸和共轭亚油酸,已被研究证实能够通过抑制促脂肪细胞信号-过氧化物酶体增殖物激活受体的表达,从而减少脂肪的生成并提升脂肪细胞中的脂肪氧化[69-72]。此外,研究指出,SCFAs能够与G蛋白偶联受体GPR41和GPR43相互作用,从而刺激肠道分泌胰高血糖素样肽1和其他肠促胰岛素的增加,进而增强饱腹感。此外,SCFAs可作为诱导剂激活肌肉中的AMP活化蛋白激酶,增加胰岛素敏感性和脂肪酸氧化,减少脂质积累[73]。GREEN等[74]认为益生菌类功能性乳制品对抗肥胖除了与SCFAs有关、还可能通过降低管腔pH值、调节细胞因子的产生及肠-脑信号传导从而促进饱腹感以及增强氧化代谢(图4)。
图3 肠道菌群对阿尔兹海默症的影响[55]
Fig.3 Effect of intestinal flora on alzheimer’s disease
图4 添加益生菌开发的功能性乳制品对肥胖和代谢综合症的影响机制[75]
Fig.4 Effect mechanism of functional dairy products developed by adding probiotics on obesity and metabolic syndrome
2.4 降低糖尿病及心脑血管疾病的发生率
心脑血管疾病是导致全球死亡率增加的主要原因,因此是卫生保健系统面临的主要挑战。长期以来,饮食模式,尤其是脂肪摄入,与心脑血管疾病风险之间存在密切的关联。特别是大量摄入饱和脂肪酸(saturated fatty acid, SFAs)和反式脂肪酸(trans fatty acid, TFAs)被直接关联到心血管疾病风险的增加,这种影响主要通过升高血浆LDL水平及促进动脉粥样硬化形成过程来介导[75]。乳制品在预防心脑血管疾病方面被认为具有一定的潜力。某些功能性乳制品如酸奶、开菲尔和奶酪,已被报道显著降低了与心脑血管疾病有关的风险生物标志物[76-77]。BAKHSHIMOGHADDAM等[78]设计了一项实验,每天食用(1) 300 g含有1.5 g菊粉和动物双歧杆菌乳酸亚种的合生元酸奶;(2)300 g传统酸奶;(3)不喝酸奶(对照)。持续24 周后,合生元酸奶组的血清肝酶得到了极大改善,谷丙转氨酶、谷草转氨酶、γ-谷氨酰转移酶和碱性磷酸酶的水平显著降低。同时与对照组相比,合生元酸奶组和传统酸奶组都观察到甘油三酯(triglyceride, TG)和LDL的降低,但传统酸奶组的程度低于合生元酸奶。此外,每天摄入200 g酸奶可使总死亡率显著降低5%,心血管事件总风险降低8%[79-80]。糖尿病是一种以高血糖为特征的代谢性疾病,截止到目前,已有较多针对功能性乳制品改善糖尿病的研究(表2)。ROCHA等[81]报道了含有植物甾醇和ω-3的功能性乳制品显著降低了中度高脂血症受试者血浆的LDL浓度。先前的一项研究对3 435名巴黎人进行了3年的随访,观察到乳制品摄入量较高与2型糖尿病、血糖耐受性降低和代谢综合征的发病率较低相关[82]。TONG等[83]研究发现摄入牛奶的量特别是脱脂或半脱脂牛奶与2型糖尿病之间呈负相关关系(风险降低14%)。最近的一项研究报道了血糖含量的显著改善(即2型糖尿病患者的空腹血糖和糖化血红蛋白血浓度,这些患者均食用了添加维生素D的发酵乳制品和酸奶)[84]。此外,先前针对8个欧洲国家的16 835名健康人群和12 403名糖尿病患者参与研究证实了奶酪和发酵乳制品与糖尿病发病率之间的负相关关系。其中,每日55 g的奶酪和酸奶可使2型糖尿病的发病率降低12%[85]。艾丽艳等[86]报道称服用含植物甾醇酯的乳粉2个月,可以有效降低受试者血清中TG和LDL水平,并提高高密度脂蛋白 (high-density lipoprotein, HDL)水平。SCFAs,尤其是丁酸盐,可以通过在基因表达水平上起作用或通过激活丝裂原活化蛋白激酶(mitogen-activated protein kinase, MAPK)途径来降低血浆水平[87]。ZEPEDA-HERN
NDEZ等[88]综述了益生菌和益生元治疗2型糖尿病的作用机制,他们认为益生元和益生菌可以通过以下机制发挥作用:(1)减少氧化应激;(2)抑制促炎细胞因子;(3)增强SCFA的产生;(4)控制血糖;(5)调节肠道通透性;(6)产生生物活性肽。
表2 功能性乳制品缓解糖尿病病症的研究
Table 2 Study on functional dairy products in relieving diabetes
功能性乳制品研究对象影响参考文献酸奶(添加乳酸菌11/19-b1和乳双歧杆菌)血脂或血糖水平略高的患者低密度脂蛋白显著降低[89]开菲尔酸奶(添加嗜热链球菌、干酪乳杆菌,嗜酸杆菌和乳杆菌)2型糖尿病患者胰岛素和同型半胱氨酸水平降低,改善胰岛素抵抗[90]酸奶(添加红米糠粉)大鼠降低血清中谷丙转氨酶水平[91]酸奶(添加乳清蛋白、菊粉、钙和维生素D3)代谢综合征患者减少体脂质量和体脂百分比,提高胰岛素敏感性[92]酸奶(添加嗜酸乳杆菌La5和乳双歧杆菌Bb12)代谢综合征患者血糖和可溶性血管黏附因子水平显著降低[93]
2.5 维持骨骼健康
骨质疏松症作为一种骨骼疾病,影响着全球2亿患者,而随着全球人口老龄化趋势的不断加剧,骨质疏松的发病率也将持续上升。在这一背景下,预防骨质疏松问题成为公共卫生领域亟待解决的问题。近年来,大量学者关于功能性乳制品与骨骼健康的关系展开了深入研究。DALY等[94]发现强化维生素D的高钙牛乳能有效缓解老年人的骨流失,补充高钙牛乳(1 000 mg钙和800 IU 维生素D)2年后,牛乳摄入组腰椎骨密度显著增加,并且血清中维生素D含量显著升高。在针对健康的绝经后妇女的研究中发现发酵乳增加了血清异黄酮的可获得性,从而降低了骨量丢失的风险[95]。另一项关于10～12岁女孩的研究结果显示,通过食用奶酪增加膳食钙摄入量比在相同钙摄入量(1 000 mg/d)下以片剂形式补充钙更有利于皮质骨矿物质量的累积[96]。研究表明,在乳制品中添加罗伊氏乳杆菌可减少75～80岁低骨密度女性的骨质流失[97]。此外,乳酸杆菌、双歧杆菌的添加可降低绝经后妇女的骨更新[98]。MARKOWIAK等[99]的研究显示,燕麦奶中的低聚果糖具有很强的益生元特性,食用后会增加SCFAs(丁酸盐、乙酸盐、丙酸盐)的产生,降低结肠中的pH值,并减少氮终产物和粪便酶的量,从而改善免疫系统功能并增加骨量。也有研究表明低聚半乳糖和低聚果糖可增加双歧杆菌的百分比,从而抑制骨质疏松症的发展[100]。胰岛素样生长因子1(insulin-like growth factor 1, IGF-1)是操控骨骼生长的重要因素,有研究显示健康的绝经后妇女食用钙强化奶酪降低了骨吸收生物标志物(抗酒石酸酸性磷酸酶)血清浓度,并增加了血清IGF-I的浓度[101]。多数人认为乳制品对骨骼健康的有益作用是钙赋予的,实际上,乳蛋白对骨骼代谢也有着重要作用,并且这可能归因于乳蛋白及其衍生的生物活性肽,可通过激活Wnt和骨形成蛋白(bone morphogenetic protein, BMP)/转化生长因子-β(transforming growth factor-β,TGF-β)信号通路发挥成骨活性。此外,乳制品中芳香族氨基酸的强化也会增加IGF-I的浓度并刺激肠道对钙的吸收[102]。随着研究的不断深入,功能性乳制品与骨骼健康的具体机制也被大量研究,据报道,肠道微生物群可能是连接二者的重要“桥梁”[103]。肠道菌群通过产生生物活性化合物(如SCFAs、吲哚衍生物、多胺和胆酸),从而影响肠外细胞并调节免疫反应,而免疫细胞被报道与骨细胞相关(图5)。
图5 肠道菌群对骨代谢的作用机制[104]
Fig.5 Mechanism of intestinal flora on bone metabolism
2.6 保持口腔健康
维持口腔健康是保证身体康健的必要条件,而口腔微生物对平衡口腔微生态至关重要。目前调节口腔微生物的新技术不胜枚举(图6),其中,通过饮食干预(补充益生菌和益生元)被广泛接受。因此将益生菌和益生元应用到功能性乳制品从而达到缓解口腔疾病的目的具有广泛的应用前景。乳制品衍生的脂质可能具有保护作用,通过在牙釉质表面形成涂层,从而减少牙釉质表面的脱矿质。LEMPERT等[105]以3～6岁儿童为实验对象,探究乳制品摄入量与龋齿发展之间的关联,发现乳制品以及乳制品成分(如乳清和酪蛋白)的摄入量与未来龋齿发展的减少有关。FERRAZZANO等[106]证明酸奶中的酪蛋白磷酸肽能够抑制脱矿质并增强牙釉质再矿化。最近的试验研究表明,乳酸杆菌和双歧杆菌可能通过抑制口腔中的链球菌和念珠菌发挥有益作用[107]。益生菌可以产生不同的抗菌成分,如有机酸、H2O2、过氧化碳、双乙酰、低分子质量抗菌物质、细菌素和黏附抑制剂,这些成分也会影响口腔菌群[108]。PANAHIPOUR等[109]的数据表明发酵乳制品在体外口服成纤维细胞中具有强大的抗炎活性。此外,奶酪还可以通过在牙菌斑中释放大量的钙和无机磷酸盐来降低致龋性,从而减少脱矿量和增强再矿化。目前已经提出了奶酪可以降低致龋性的几种机制:(1)刺激唾液流动,并促进唾液化合物的缓冲作用,中和斑块酸;(2)抑制牙菌斑细菌,减少细菌负荷,从而减少酸的产生[110]。
3 展望
近年来,我国乳制品行业的发展越来越快,行业结构也在不断完善,功能性乳制品作为乳制品行业的主力军,为改善消费者健康和营养状况提供了诸多益处,它们潜在的功能属性也在不断被挖掘,其在行业的市场价值将持续攀升。但不可否认的是,它们的功效和健康促进作用必须在更大规模的临床研究中得到证实,这也是学术界和工业界将面对的挑战。此外,消费者多样化的需求也不断推动着该行业的发展,这也就需要科研人员深入探讨其发挥功效的潜在作用机制,进而揭示功能性乳制品在食品领域的巨大潜力。
图6 调节口腔微生物的新技术[111]
Fig.6 Current and novel techniques to modulate dysbiotic oralome
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