Human milk glycosaminoglycans as possible bioactive substances for the breastfed newborn.
Human milk glycosaminoglycans as possible bioactive substances for the breastfed newborn.
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DOI：
10.1089/bfm.2012.0052
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发表时间：
2013-04
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影响因子：
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通讯作者：
G. Coppa;O. Gabrielli;L. Zampini;E. Bertino;N. Volpi
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文献类型：
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作者：
G. Coppa;O. Gabrielli;L. Zampini;E. Bertino;N. Volpi
最近，第一个完整的特性和定量评价的糖胺聚糖（GAG）在人和牛的牛奶已经报道。硫酸软骨素和肝素分别占总人乳GAG的约55%和约42%，而硫酸皮肤素和透明质酸占剩余的3%。相比之下，在代表婴儿配方食品的起始材料的牛乳中，硫酸皮肤素构成了主要成分（约40%）。此外，牛乳中GAG的总量比人乳低约7倍（分别为60.2 mg/L和416.2 mg/L）。在随后的一项研究中，对哺乳期第一个月内分娩足月或早产新生儿的母亲乳汁中的GAG含量进行了评价。在两种乳汁中均观察到GAG浓度逐渐降低，早产儿乳汁中的绝对量始终显著较高。在初乳中发现了最高值（在哺乳期第4天，早产和足月乳中分别为9.3和3.8 g/L），随后逐渐降低，直至第30天（分别为4.3和0.4 g/L）。从上述数据可以推断，母乳喂养的婴儿每天摄入一致量的GAG。在结构上，乳GAG是在乳腺的肺泡细胞中通过特异性糖基转移酶的顺序作用合成的硫酸化线性多糖。由于缺乏分泌在胰液中或存在于肠壁上的特异性糖苷酶和硫酸酯酶，我们可以假设，一旦摄入，人乳GAG可以以完整的形式到达小肠。越来越多的证据表明，许多微生物（病原菌、病毒和寄生虫）结合肠上皮细胞的GAG链，以有效侵入和繁殖。因此，作为可溶性受体类似物的游离GAG可以在预防和保护母乳喂养的婴儿免受肠道感染方面发挥重要作用。此外，据报道，母乳喂养的新生儿比配方奶粉喂养的新生儿产生更少的氧化应激。由于硫酸软骨素（和其他GAG）是众所周知的抗氧化剂和抗炎剂，其通过激活能够诱导抗氧化酶的蛋白激酶C/磷酸肌醇3-激酶/Akt信号传导途径起作用，因此这些大分子可以有助于人乳的抗氧化特性，这在新生儿期特别重要。最后，由于双歧杆菌具有参与复杂碳水化合物代谢的特定酶，我们可以推测到达结肠的未消化的GAG可能表现为益生元，有助于母乳喂养婴儿典型的生物合成植物群的发育（正在进行研究以评估人乳GAG的这种可能能力）。
Recently the first complete characterization and quantitative evaluation of glycosaminoglycans (GAGs) in both human and bovine milk have been reported. Chondroitin sulfate and heparin represent, respectively, approximately 55% and approximately 42% of the total human milk GAGs, whereas dermatan sulfate and hyaluronic acid make up the remaining 3%. In contrast, in bovine milk, which represents the starting material for infant formulas, dermatan sulfate constituted the main component (approximately 40%). Moreover, the total amount of GAGs in bovine milk is approximately seven times lower compared with human milk (60.2 mg/L vs. 416.2 mg/L, respectively). In a subsequent study, the GAG content in the milk from mothers delivering term or preterm newborns during the first month of lactation has been evaluated. A progressive decrease of GAG concentration was observed in both milks, with absolute amounts being consistently significantly higher in preterm milk. The highest values were found in colostrum (9.3 and 3.8 g/L in preterm and term milk, respectively, at Day 4 of lactation), followed by a progressive decrease up to Day 30 (4.3 and 0.4 g/L, respectively). From the above data it can be deduced that breastfed infants daily ingest consistent amounts of GAGs. Structurally, milk GAGs are sulfated linear polysaccharides synthesized in alveolar cells of the mammary gland by the sequential action of specific glycosyl transferases. Because of the absence of specific glycosidases and sulfatases secreted in the pancreatic juice or present on the intestinal wall, we can suppose that, once ingested, human milk GAGs can reach the small intestine in intact form. Accumulated evidence indicates that many microorganisms (pathogenic bacteria, viruses, and parasites) bind GAG chains of enterocytes for efficient invasion and propagation. As a consequence, the free GAGs, acting as soluble receptor analogs, could play an important role in preventing and protecting breastfed infants from intestinal infections. Moreover, it has been reported that breastfed newborns develop less oxidative stress than formula-fed ones. As chondroitin sulfate (and other GAGs) are well-known antioxidant and anti-inflammatory agents that act by activating the protein kinase C/phosphoinositide 3-kinase/Akt signaling pathway able to induce antioxidant enzymes, these macromolecules can contribute to the antioxidant properties of human milk, which are particularly important during the neonatal period. Finally, as bifidobacteria possess specific enzymes involved in the metabolism of complex carbohydrates, we can speculate that the undigested GAGs reaching the colon may behave as prebiotics to contribute to the development of bifidogenic flora, typical of breastfed infants (studies are in progress to evaluate this possible capacity of human milk GAGs).