母乳是婴儿最理想的天然功能性食品,含有丰富的营养成分和生物活性物质。其中,母乳低聚糖(Human milk oligosaccharides,HMOs)为母乳中独有的、具有结构多样性的一类游离的低度聚合糖,是仅次于乳糖和脂肪的第三大营养素。早期学者认为其具有促进双歧杆菌增殖的作用,也称其为“双歧因子”(1, 3)。目前普遍认为HMOs是母乳中天然的益生元,可通过不同方式发挥抗病原体黏附、免疫调节等作用(4-7),对婴儿健康生长发育至关重要。
1.HMOs的基本概述
人类对HMOs的研究始于19世纪末,20世纪中叶科学家首次发现双歧因子为低聚糖分子,迄今为止已鉴定出超过200种HMOs分子(1, 4)。一般来说,HMOs分子是由3-22个寡糖通过糖苷键以不同的比例组合而成,包括D-葡萄糖(Glc)、D-半乳糖(Gal)、N-乙酰葡萄糖胺(N-acetylglucosamine,GlcNAc)、L-岩藻糖(Fucose,Fuc)和N-乙酰神经氨酸(Neu5Ac,或唾液酸Sialic Acid)5种基本结构单位(4, 8)。根据分子末端连接的单体将其分三类:岩藻糖基化中性HMOs、非岩藻糖基化中性HMOs,以及唾液酸化酸性HMOs。其中,中性HMOs占总HMOs分子的75%以上,而唾液酸化酸性HMOs仅占12%-14%(2)。
HMOs的种类和含量受多种因素的影响,如基因、体质指数、胎龄、饮食习惯、所处的地理环境(4, 9, 10)等。分泌基因(Se或FUT2)和Lewis基因(Le或FUT3)分别表达α1,2-岩藻糖基转移酶和α1,3/4-岩藻糖基转移酶,导致Se / Le 和Se /Le-的分泌型母乳中含较高浓度的α1,2-岩藻糖化HMOs,如2’-岩藻糖基乳糖(2’-fucosyllactose,2’-FL)和乳糖-N-岩藻五糖(lacto-N-fucopentaose,LNFP)Ⅰ,而非分泌型母乳中缺乏该类HMOs(4, 9)。除此之外,同一母体在不同泌乳时期的HMOs含量也存在差异,初乳中HMOs含量达20-25g/L,而成熟乳中则降低到约为5-20g/L(2)。
2.HMOs的生物活性作用
2.1调节肠道菌群
HMOs 经口摄入人体后,大部分能耐受胃酸和小肠消化酶的分解,直接运送至结肠,作为碳源被双歧杆菌属和拟杆菌属等肠道微生物选择性利用,促进这些有益菌定植和生长(7, 11-13)。研究发现,长双歧杆菌可借助两种不同的岩藻糖基乳糖转运蛋白,吸收并利用岩藻糖基化HMOs,刺激自身与人类的进化共生(11)。部分细菌在代谢HMOs后会产生短链脂肪酸等,进一步营造了酸性的肠道环境,抑制有害菌的生长,从而调节婴儿肠道微生物的构成(13, 14)。
2.2抗病原体黏附作用
HMOs与肠道上皮细胞具有结构相似的抗原表位,充当病原体的可溶性诱饵,竞争性结合病原体,阻止其与宿主细胞的黏附(6, 15)。HMOs还可直接作用于肠道上皮细胞,改变细胞表面聚糖,使病原体无法与肠道上皮细胞结合,作为抗黏附剂,发挥抗感染的作用(4, 16)。多项体外实验证实HMOs可抵御诺如病毒、流感病毒、轮状病毒,甚至人类免疫缺陷病毒(Human Immunodeficiency Virus,HIV),并且对肺炎链球菌、铜绿假单胞菌、致病性大肠杆菌等细菌、毒素和溶组织内阿米巴具有高效的抑制作用(15, 17-20)。
2.3免疫调节作用
HMOs能直接刺激杯状细胞增殖,调节肠道上皮细胞的基因表达,影响肠道屏障功能,进而直接或间接调节婴儿黏膜免疫和全身免疫(2, 5)。特定的HMOs可抑制单核细胞、淋巴细胞和中性粒细胞黏附于内皮细胞表面,从而发挥抗炎作用(21)。尤其是酸性HMOs,它可以在体外诱导白细胞介素-10和γ-干扰素的产生,还能抑制过敏易感人群中的过敏原相关的Th2型免疫反应,调节Th1/Th2平衡关系(22)。
未完待续
参考文献
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