低聚果糖与低聚半乳糖在婴幼儿配方乳粉中的精准化应用

2021-08-17 本站原创 620


摘要:母乳是婴幼儿营养配方的金标准,而低聚糖是母乳重要的活性成分。我国母乳喂养婴幼儿平均每天摄入3.5~6.4g母乳低聚糖,而婴幼儿配方乳粉(以下简称“婴配粉”)喂养婴幼儿平均每天摄入的低聚果糖与低聚半乳糖仅0.6~3.0g。为精准模拟母乳低聚糖的作用,低聚果糖与低聚半乳糖的含量至关重要。因此,低聚果糖与低聚半乳糖在婴配粉中的添加量有必要适当提高。

关键词:母乳低聚糖;低聚果糖;低聚半乳糖;婴幼儿配方乳粉


0 引言


母乳是婴幼儿营养配方的金标准[1]。母乳喂养最佳方式是从出生后1 h以内开始,至少6 个月的纯母乳喂养及母乳辅食混合喂养至2 岁或以上[2]。然而,受各种因素的影响,全球母乳喂养率低于40%[3],而我国0~6 月婴儿纯母乳喂养率只有27%[4]。因此,婴幼儿配方乳粉(以下简称“婴配粉”)新国标(《GB 10765—2021食品安全国家标准 婴儿配方食品》《GB 10766—2021食品安全国家标准 较大婴儿配方食品》和《GB 10767—2021食品安全国家标准 幼儿配方食品》)调整了营养素指标,旨在最大限度模拟母乳功能,从而促进婴幼儿健康成长。其中,为模拟母乳低聚糖(Human milk oligosaccharides, HMO)的作用,婴配粉通常添加低聚果糖(Fructo-oligosaccharides, FOS)与低聚半乳糖(Galacto-oligosaccharides, GOS)。


1 母乳低聚糖的作用


1.1 调节肠道菌群

HMO在婴儿肠道菌群的形成和健康维持方面发挥着关键作用[5]。研究表明,只有1%的HMO被吸收到循环系统中,其余的则被肠道微生物代谢并通过粪便和尿液排出体外[6]。新生儿肠道微生物在利用HMO的能力上存在差异[7]。HMO可促进肠道内双歧杆菌和拟杆菌等有益菌的生长,通过增殖有益菌“战胜”潜在病原微生物来防止感染[8~11]

1.2 预防病原体,调节免疫

HMO通过模拟受体糖链结构而结合病原体,从而抑制病原体黏附到宿主细胞,防止病原体入侵[12]。HMO对某些病原体有直接的抵抗作用[10]。HMO还可以调节肠上皮细胞的反应来发挥免疫调节剂的作用,通过减少细胞生长、诱导分化和凋亡来改变肠道环境,改变T细胞对平衡的Th1/Th2细胞因子的反应来改变免疫反应[13,14]

1.3 预防坏死性小肠结肠炎(NEC)

NEC是早产儿中最常见、最致命的疾病之一[15]。5%~10%的出生体重极低婴儿(小于1 500 g)会发生NEC,其中超过1/4的婴儿死亡,幸存者也会面临严重的神经并发症[16~18]。母乳喂养的婴儿患NEC的风险要比服用婴配粉的婴儿低6~10 倍,其中HMO发挥关键作用[19]

1.4 促进大脑发育

母乳喂养的早产儿在18 月时发育得分更高,到7 岁时的智商也更高[20]。有证据表明,大脑发育和认知部分依赖于唾液酸[21,22]。唾液化的HMO是母乳中唾液酸的主要来源,有助于婴儿获得更高的智商和更好的发育[10]


2 母乳低聚糖的组成及含量


HMO是由相对少量的不同单糖形成的复杂碳水化合物聚合物,其结构、大小、复杂性均不同,主要受母体遗传的影响[23~26]。目前鉴定出的HMO分子有200 多种[27]

HMO的浓度在个体之间和哺乳期之间有所不同,这种差异会随着婴幼儿生长期的不同生理需求变化,从而协调婴儿胃肠道微生物群的逐步发展[28~30]。HMO在初乳中含量多达20.0~25.0 g/L,成熟母乳中含量下降到5.0~20.0 g/L[10]。我国母乳HMO平均含量为4.5~9.2 g/L[31]。母乳中的低聚糖浓度是牛奶的100~1 000 倍[32]。母牛产后立即收集的牛初乳中低聚糖质量浓度约为1.0 g/L,在48 h后质量浓度迅速降低,而山羊乳含量更低,仅为250~300 mg/L[33,34]


3 采用低聚果糖与低聚半乳糖模拟母乳低聚糖的作用


益生元是被微生物选择性利用从而赋予宿主健康效益的一类物质[35],包括低聚果糖(FOS)、低聚半乳糖(GOS)、HMO。FOS由果糖基以β-2,1糖苷键连接而成,聚合度为2~9。GOS是以乳糖为原料,经β-半乳糖苷酶催化水解半乳糖苷键,并通过转半乳糖苷的作用将水解下来的半乳糖苷转移到乳糖分子,从而生成GOS,聚合度为2~8。GOS和FOS是被允许加入婴配粉的两种益生元。研究表明,婴配粉中添加FOS和GOS,可以模拟HMO诸如调节肠道菌群、促进排便、提高免疫、减少感染、缓解过敏及特应性皮炎等的作用[36~45]。                                                                                                                                                                                                                                                                   

4 低聚果糖与低聚半乳糖的含量对于精准模拟母乳低聚糖的作用至关重要


FOS与GOS模拟HMO的效果受不同因素的影响。其中,FOS与GOS的含量对于精准模拟母乳低聚糖的作用至关重要。

Euler等[46]进行的一项针对2~6 周龄的健康足月婴儿试验发现,无论奶粉中添加1.5 g/L或3.0 g/L(约1.05 g/100 g或2.10 g/100 g)FOS,粪便中的肠球菌和拟杆菌都没有发生明显变化,未实现改善肠道菌群的目的。在抑制艰难梭菌毒素的产生方面也没有显著效果。而母乳喂养的婴儿这些指标均有明显变化。

Brunser等[47]对90 名近4 个月大的婴儿进行的一项随机对照试验发现,服用2.0 g/L(约1.40 g/100 g)FOS对双歧杆菌、乳酸杆菌等有益菌没有明显增殖效果。

Takumi等[48]的研究让不同年龄段的婴幼儿分别服用不同剂量的FOS(0~1 岁:1 g;2~3 岁:2 g;4~5 岁:3 g),结果发现,只有0~1 岁婴儿服用FOS后可以增殖普拉梭菌,而2~5 岁的幼儿每天服用2 g或3 g的FOS并无明显效果。

Bakker-Zierikzee等[49]给婴儿服用含6.0 g/L(约4.20 g/100 g)的FOS和GOS混合物,结果发现,在试验前期,服用FOS+GOS组婴儿粪便中的醋酸、丁酸等短链脂肪酸含量要低于母乳喂养婴儿,后期才逐渐无差异。母乳喂养组前期pH值也更低,在16 周后两组才基本一致。而较低的肠道pH值不利于有害菌的定殖。同样的使用剂量下还有研究发现,FOS+GOS促进婴儿产生分泌型免疫球蛋白A(sIgA)的速度也更慢,直到第28周以后才能基本达到母乳喂养婴儿水平[50]。sIgA是人体内最丰富的免疫球蛋白之一,是黏膜表面的主要免疫球蛋白,在胃肠道防御机制中发挥关键作用,抑制潜在有害抗原在黏膜组织的黏附和入侵,中和来自微生物病原体的毒素和毒力因子[51]

服用添加量为8.0 g/L(约5.60 g/100 g)的奶粉后,对婴儿肠道双歧杆菌的生长和微生物的代谢活性有促进作用,而在短链脂肪酸、乳酸和pH值等的变化方面也与母乳喂养婴儿更接近[52]。婴儿粪便状态、大便频率、每天体重增加情况也与母乳相似[53];此添加量也提高了胃动素含量,增强胃动力,减少胃液残留,同时还降低了胆固醇和低密度脂蛋白胆水平,具有降低血脂的保护作用[54];还有研究发现,此剂量可降低过敏高危婴儿免疫球蛋白游离轻链(Ig-fLC)的血浆浓度,从而降低了婴儿发生特应性皮炎的发病率[55]

另一项研究则发现,在早产儿婴配粉中添加10.0 g/L(约7.00 g/100 g)的GOS和FOS混合物可刺激肠道双歧杆菌的生长,其粪便特征与母乳喂养的早产儿相似。这两种益生元混合物有助于提高早产儿的肠道耐受性[56]


5 低聚果糖与低聚半乳糖在婴配粉中的应用现状


母乳HMO平均含量为4.5~9.2 g/L[31],而婴儿平均每天摄入母乳690~770 mL[57]。因而,我国母乳喂养婴幼儿平均每天摄入3.5~6.4 g母乳低聚糖。目前,国内婴配粉建议服用量多为每天60~130 g,而婴配粉中FOS和(或)GOS的添加量为1%~3%(w/w)。婴配粉喂养婴幼儿平均每天摄入的FOS和(或)GOS仅0.6~3.0 g。由此可见,国内婴配粉的FOS和(或)GOS添加量低于婴幼儿正常需求。相对而言,国外婴配粉的FOS和(或)GOS添加量较高(表1)。根据我国对FOS和GOS在婴幼儿配方食品中使用的法规要求:低聚果糖(或低聚半乳糖)作为益生元类物质的来源之一,该类物质在婴儿配方食品、较大婴儿和幼儿配方食品中总量不超过64.5 g/kg”,即6.45%,此限值基本与国外婴配粉中的添加量一致。但是我国目前相关产品中添加量远低于此限值,多是概念性添加,这种低剂量的添加是否能真正起到模拟HMO的作用值得探讨。

表1  国内外婴配粉中FOS/GOS添加量对比

产地

品牌

FOS/GOS添加量(g/100 g

国内

品牌1

FOS0.50

GOS0.47

品牌2

FOS0.85

GOS0.85


品牌3

FOS0.10

GOS1.40


品牌4

GOS3.0


品牌5

GOS3.0


国外

品牌1

FOS0.61

GOS5.49

品牌2

FOS0.59

GOS5.31


品牌3

FOS0.59

GOS5.31


品牌4

FOS+GOS8.70


品牌5

FOS3.90



6 小结


婴幼儿时期是身体和智力发育的关键期。而母乳作为婴幼儿营养配方的黄金标准,是婴幼儿最安全、最天然的食物,其不仅含有多种免疫蛋白和生长因子,而且还包含成分复杂却功能多样的母乳低聚糖。由于多种原因造成部分宝宝无法摄入足够量的母乳,因此,尽可能模拟母乳营养成分的婴配粉便成为营养替代品的首选。

母乳低聚糖由于其成分复杂且种类繁多,尚无法全部人工合成。目前国外可合成并使用的有2’-岩藻糖基乳糖(2’-fucosyllactose,2’-FL)和乳酰-N-新四糖(lacto-N-eotetraose,LNnT)两种成分。而我国本土HMO的相关研究比较滞后,加之法律方面的限制,目前尚无法使用,多采用添加益生元的方式来模拟HMO的功效,其中以FOS和GOS为主。虽然已发现FOS和GOS在部分功效上已经和HMO差异不大,但其使用却还是存在诸多盲目性,添加量不足便是其中之一,这一点在国产品牌产品中尤为突出。目前已有多个研究发现,较低的添加量无法对婴儿健康产生有益作用,达不到模拟HMO的效果。因此,加大对我国母乳HMO的研究,同时加大对婴配粉中FOS、GOS等低聚糖的用量配比、有效添加量、与其他营养素的关系等内容研究,将为今后指导和改进婴幼儿配方奶粉,使其更接近我国母乳,更有利于我国婴幼儿的发育成长打下坚实的科学基础。


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