母乳低聚糖的体内代谢与体外合成研究进展

母乳低聚糖（human milk oligosaccharides，HMOs）是母乳中独特的营养成分，结构复杂，种类繁多，不同的HMOs可能具有不同的功能。本文在HMOs的个体差异性、结构多样性与功能活性方面介绍了HMOs的最新研究进展，重点阐述了HMOs在人体内的代谢途径以及体外的合成途径，最后阐述了HMOs在婴儿配方粉中的应用现状，提出了研究及应用中面临的问题。HMOs的应用是婴儿配方奶粉发展中的重大突破，缩小了配方奶粉喂养儿在肠道菌群组成、免疫功能以及认知等方面上与母乳喂养儿的差距。HMOs的深入研究为新型婴儿配方奶粉的开发提供理论依据。     

低聚半乳糖与婴幼儿健康关系的研究进展

低聚糖是重要的营养与免疫调节物质,与婴幼儿早期生长发育密切相关。作为一种常见的功能性食品添加剂,低聚半乳糖(GOS)具有类似母乳低聚糖(HMOs)的功能,可能对调节婴幼儿肠道菌群、改善肠道功能、促进免疫及预防过敏等起到有益作用。从GOS的结构、功能出发,对强化GOS配方食品的喂养效果进行综述,并对其前景进行展望,以期为GOS在婴幼儿配方食品中的合理应用提供科学依据。     

低聚果糖与婴幼儿健康关系的研究进展

母乳中的低聚糖对婴幼儿健康发挥重要作用。低聚果糖(FOS)是常用来模拟母乳中低聚糖的配方奶粉添加剂之一,可能有助于婴幼儿改善肠道菌群、调节肠道功能、预防过敏及促进矿物质吸收。本文对FOS结构功能以及与婴幼儿健康的关系进行综述,为FOS在婴幼儿营养方面的合理应用提供科学依据。     

母乳低聚糖(HMOs)的科学共识

母乳低聚糖(human milk oligosaccharides, HMOs)是母乳中含量第三的固体成分,在支持婴幼儿特征肠道菌群建立和免疫等方面发挥重要作用,其发现、制造与应用对于促进人群健康,尤其在改善婴幼儿健康和营养需求方面具有里程碑式的意义。目前,HMOs已在100余个国家和地区批准和/或上市使用。其生产方式主要以微生物发酵法为主,产品结构与母乳中的HMOs完全一致。相关临床人群实验和动物毒理实验以及多年使用历史均证明其用于婴幼儿配方食品等是安全的。为了促进我国婴幼儿配方食品、特殊医学用途配方食品等领域的高质量发展和产业升级,服务更多消费者营养健康需求,中国食品科学技术学会组织食品科学、临床医学、生物发酵、食品营养等领域专家与产业界代表,通过现场咨询、文献检索和专题研讨等形式,广泛讨论形成对母乳低聚糖的科学共识,以推动HMOs在中国食品行业的合法使用。     

母乳低聚糖的结构与功能研究进展

母乳低聚糖(human milk oligosaccharides, HMOs)是人乳中仅次于乳糖和脂肪的第三大营养物质,是母乳的独特成分,在婴幼儿生长发育中起到重要作用。每种母乳低聚糖可能具有不同的功能。本文阐述了母乳低聚糖结构组成、功能作用机理以及应用现状,为婴幼儿配方食品的设计、开发提供理论支持。     

2’-岩藻糖基乳糖的功能、合成及应用研究进展

2’-岩藻糖基乳糖(2’-fucosyllactose,2’-FL)在母乳低聚糖(human milk oligosaccharides,HMOs)中含量最高,研究证明2’-FL具备调节婴儿肠道菌群平衡、抵抗病原体的黏附、免疫调节和促进婴儿大脑神经发育等功能。合成2’-FL的方法有化学合成法、酶法合成法与全细胞合成法。2’-FL已经进入商业化生产阶段,其产业化受到产量、成本、品质及安全等因素的制约,需要在合成宿主、碳源的选择等方面进一步开展相关研究。2’-FL已被美国和欧洲联盟等国家批准可添加至婴幼儿配方食品及膳食补充剂中,研究证明添加了2’-FL的婴幼儿配方奶粉在营养成分和功效上更贴近母乳。本文综述了2’-FL的结构、母乳中的含量及其生理功能,总结了现阶段2’-FL的制备方法和应用情况,展望了2’-FL未来的研究方向,为2’-FL在婴幼儿配方食品中的开发及应用提供理论支持。     

母乳低聚糖的研究进展

母乳中母乳低聚糖(HMOs)含量丰富且独特,在已知的200种成分中,有157种结构被阐明。HMOs不仅具有"双歧因子"效果,还具有抗黏附、抗菌、调节肠道上皮细胞和免疫细胞,减少过度的黏膜白细胞浸润和活化,降低新生儿坏死性小肠结肠炎等功效,并为婴幼儿大脑发育和认知提供唾液酸作为潜在的必要营养素。由于HMOs大规模生产受限,因此化学和生物模拟的HMOs代替品不断出现。虽然经典的代替品,如低聚半乳糖和低聚果糖具有HMOs部分功效,但是其结构组成差异明显,部分国家批准上市的2'-岩藻糖基乳糖(2'-FL)和乳糖-N-新四糖(LNnT)只是模拟了HMOs中一种或几种分子结构。富集牛乳低聚糖作为HMOs替代品具有明显优势。本文综述母乳低聚糖不同泌乳期含量、分型、结构特征、分析方法、生理功能、消化吸收和模拟,介绍牛乳低聚糖产业化模拟母乳低聚糖的可能性,旨在为HMOs替代品的研究、开发与产业化提供理论参考。     

母乳脂质对婴儿肠道功能影响研究进展

婴幼儿出生后免疫系统不成熟,依赖先天免疫系统进行保护,肠道是先天免疫的重要执行者。母乳提供了婴幼儿足够数量的脂质和最适宜消化吸收的脂质结构,脂质以乳脂肪球的形式存在并被乳脂肪球膜所包裹。母乳脂质的结构、组成也直接影响对婴幼儿肠道功能的调节。本文对母乳中饱和脂肪酸、长链多不饱和脂肪酸和脂肪球膜以及复合脂质在婴儿肠道发育和免疫调节方面的作用做一综述。为婴幼儿配方奶粉母乳化的应用以及婴儿肠道疾病的治疗提供新的理论支撑。     

低聚糖和Sn-2棕榈酸甘油酯对婴儿肠道有益菌影响的临床研究进展

母乳富含的低聚糖及Sn-2棕榈酸甘油酯对婴儿肠道有益菌群增殖有促进作用。与母乳喂养儿相比,喂养婴儿奶粉显著降低婴儿肠道有益菌数量。由于肠道菌群可能影响婴儿的生长发育和成人期健康,缩小两种喂养方式造成的婴儿肠道菌群差异,是学术研究和商业开发的方向。本文综述了喂养添加低聚糖或Sn-2棕榈酸甘油酯的婴儿奶粉对婴儿肠道有益菌含量影响的临床研究并讨论现存研究存在的问题,为开发有益肠道健康婴儿奶粉提供思路。     

配方奶粉和母乳中结构脂质差异及其对婴幼儿生理功能的影响研究进展

母乳喂养和配方奶粉喂养婴儿的差异可以归因于母乳中多种成分在数量和质量上与配方奶粉的不同,特别是甘油三酯的结构和类型。本文基于国内外不同配方奶粉和母乳中结构脂质差异的研究现状,对两者结构脂质差异、消化与吸收过程、粪便排泄、脂肪酸代谢等作用分别进行了综述,并就不同结构脂质对婴幼儿生理健康的影响进行了总结归纳。     

Relationship Between Oligosaccharides and Glycoconjugates Content in Human Milk and the Development of the Gut Barrier

The intestinal immune barrier is considered to be the gatekeeper of the human body and rapidly develops directly after birth. Many pre‐ and postnatal factors influence the development of the gut‐barrier, which is composed of the microbiota, the mucus, the epithelial layer and the mucosal immune system. Even minor disturbances during barrier development can have consequences for health far into adulthood. Here we critically discuss the current knowledge on which pre‐ and postnatal factors influence development, maturation, and maintenance of the gut immune barrier. Human milk has a unique composition and is the gold standard for adequate development of the intestinal immune barrier. Not only the influence of human milk oligosaccharides (HMOs) but also that of glycoproteins (HMGPs) is reviewed. We discuss the influence of maternal genetic factors, such as the secretor and Lewis phenotypes on breast milk fucosylation and sialylation of HMOs and HMGPs. This diversity in HMOs and HMPGs influences microbiota composition and also the development of the immune barrier. Cow milk‐derived infant formula is often being used as an alternative for human breast milk. The consequences of this for proper development of the intestinal immune barrier and, in particular, the differences in the type of oligosaccharides and glycosylation patterns (sialic and fucose composition) between cow and human milk are critically discussed. Current and prospective strategies to promote proper gut‐immune maturation are proposed. These might include more personalized infant formulas when breast milk is not an option.     

Health promoting aspects of milk oligosaccharides

Human milk contains a large variety of oligosaccharides (HMOs) with the potential to modulate the gut flora, to affect different gastrointestinal activities and to influence inflammatory processes. Human intervention or clinical studies are still missing as the large amounts of milk oligosaccharides needed are not yet available. Therefore, there is great interest in sources of oligosaccharides other than those from human milk. Although the amount of oligosaccharides in milk of most animal species is low compared with human milk, recent data indicate significant differences among milk from farm animals. Whether some of these oligosaccharides are good candidates for human studies needs to be further investigated. Currently, there is only a limited amount of quantitative data on the total amount of oligosaccharides and on individual components in animal milk, e.g., in bovine, goat or buffalo milk. Regarding biological functions certain structural prerequisites are necessary for milk oligosaccharides to be effective in different in vitro systems. Often prebiotic oligosaccharides (PBOs) from plants are obtained by technological means and are considered to be similar or even identical to HMOs. However, there is no evidence for this speculation as PBOs are structurally quite different from HMOs. Whether PBOs exert comparable functional effects remains to be investigated. If this were the case their addition to infant formula may be useful in the context of mimicking biological functions of human milk constituents.     

Non-digestible carbohydrates in infant formula as substitution for human milk oligosaccharide functions: Effects on microbiota and gut maturation

Human milk (HM) is the golden standard for nutrition of newborn infants. Human milk oligosaccharides (HMOs) are abundantly present in HM and exert multiple beneficial functions, such as support of colonization of the gut microbiota, reduction of pathogenic infections and support of immune development. HMO-composition is during lactation continuously adapted by the mother to accommodate the needs of the neonate. Unfortunately, for many valid reasons not all neonates can be fed with HM and are either totally or partly fed with cow-milk derived infant formulas, which do not contain HMOs. These cow-milk formulas are supplemented with non-digestible carbohydrates (NDCs) that have functional effects similar to that of some HMOs, since production of synthetic HMOs is challenging and still very expensive. However, NDCs cannot substitute all HMO functions. More efficacious NDCs may be developed and customized for specific groups of neonates such as pre-matures and allergy prone infants. Here current knowledge of HMO functions in the neonate in view of possible replacement of HMOs by NDCs in infant formulas is reviewed. Furthermore, methods to expedite identification of suitable NDCs and structure/function relationships are reviewed as in vivo studies in babies are impossible.     

Bifidobacterial utilization of human milk oligosaccharides

A promising strategy to improve health is the rational manipulation of one's beneficial microbiota via dietary interventions. This is observed in nature where specific bifidobacteria utilize human milk oligosaccharides (HMOs) that are encountered within the breast-fed infant colon. Bifidobacterium longum subsp. infantis is regarded as the archetypical HMO consumer associated with the developing neonate. This review summarizes the known molecular mechanisms underlying HMO utilization, as determined for bifidobacterial commensals. In addition, future directions of HMO research are discussed with an emphasis on physiological, ecological and clinical approaches to understand bifidobacterial utilization of this intriguing substrate.     

Longitudinal changes of human milk oligosaccharides,breastmilk microbiome and infant gut microbiome are associated with maternal characteristics

Human milk oligosaccharides (HMOs) play an important role in infant health. This study aimed to investigate the association of maternal characteristics with HMOs, human breastmilk (HBM) microbiome and infant gut microbiome over the first three months of lactation. Chinese mothers and infant pairs (n = 110) were included in this prospective cohort. Secretor status linked with α1,2-fucosyltransferase expression was determined by the presence of total α1,2-fucosylated HMOs in HBM for 75.8% of the mothers. The concentration of dominant HMOs significantly decreased over three months except for 3’-fucosyllactose. In addition to the elevated levels of α1,2-fucosylated HMOs, other neutral HMOs significantly reduced in secretors milk. Alpha-diversity of HBM and infant gut microbiome significantly increased over time, and an elevated abundance of Bifidobacterium and decreased levels of Streptococcus, Staphylococcus and Clostridium in the infant gut microbiota were noted. Multi-association analysis indicated maternal age and body mass index significantly correlated with specific HMOs and infant growth. Our study provides pivotal data on Chinese HMOs distribution profile, and their association with maternal characteristics and the infant gut microbiome.     

Human Milk Oligosaccharides as Promising Antivirals

Human milk oligosaccharides (HMOs) are diverse unconjugated carbohydrates that are highly abundant in human breast milk. These glycans are investigated in the context of exhibiting multiple functions in infant growth and development. They seem to provide protection against infectious diseases, including a number of poorly manageable viral infections. Although the potential mechanism of the HMO antiviral protection is rather broad, much of the current experimental work has focused on studying of HMO antiadhesive properties. HMOs may mimic structures of viral receptors and block adherence to target cells, thus preventing infection. Still, the potential of HMOs as a source for new antiviral drugs is relatively unexploited. This can be partly attributed to the extreme complexity of the virus‐carbohydrate interactions and technical difficulties in HMO isolation, characterization, and manufacturing procedures. Fortunately, we are currently entering a period of major technological advances that have enabled deeper insights into carbohydrate mediated viral entry, rational selection of HMOs as anti‐entry inhibitors, and even evaluation of individual synthetic HMO structures. Here, we provide an up‐to‐date review on glycan binding studies for rotaviruses, noroviruses, influenza viruses, and human immunodeficiency viruses. We also discuss the preventive and therapeutic potential of HMOs as anti‐entry inhibitors and address challenges on the route from fundamental studies to clinical trials.     

Gangliosides in human milk and infant formula: A review on analytical techniques and contents

Gangliosides (GGs) are important bioactive compounds that offer beneficial anti-infective, anti-inflammatory, and neuronal development effects. The present work reviews the techniques used to determine the GG content in human milk and infant formula. In the case of conventional techniques (thin-layer chromatography (TLC) and spectroscopy), extraction and purification steps are more laborious than for the current techniques (liquid chromatography-mass spectrometry (LC-MS)). The new methodologies allow the identification of the ceramide and oligosaccharide forming the GGs, which is of interest considering their structural differences among human milk and infant formula. This information could be used to incorporate GGs into infant formula in such a way as to more closely resemble human milk regarding total contents and profile.     

中国母乳中低聚糖组分及含量变化——以中国广东江门地区为例

密集收取22位中国母亲共163个母乳样品,采用高效阴离子色谱法监测在不同泌乳期中22种母乳低聚糖(human milk oligosaccharides,HMOs)的组成和含量变化。结果表明,15种中性低聚糖含量在泌乳初期(初乳)达到最高值后逐渐减少(成熟乳),但是3-岩藻糖乳糖的含量在整个取样阶段均在持续增加。6种酸性低聚糖在泌乳初期稳定但后期随时间延长逐渐减少,其中唾液酸化-乳糖-N-四糖a只在部分样本中检出。基于Lewis血型类型,可将母亲分为分泌型组和非分泌型组。分泌型母亲的母乳中富含α-1-2-L-岩藻糖基化低聚糖(如2’-岩藻糖乳糖、乳酰-N-岩藻五糖Ⅰ、二岩藻糖基乳糖、乳酰-N-二岩藻六糖Ⅰ)。在分泌型与非分泌型母乳中,α-1-2-L-岩藻糖基化低聚糖的质量浓度范围分别为1 211~7 272 mg/L和100~920 mg/L;然而α-1-3/4-L-岩藻糖基化低聚糖(如乳酰-N-二岩藻六糖Ⅱ、乳糖-N-二岩藻糖基-八糖、3-岩藻糖乳糖、乳酰-N-岩藻五糖Ⅱ)的质量浓度范围则分别为181~2 722 mg/L和476~4 931 mg/L。总体表明,分泌型和非分泌型母亲在泌乳期内的HMOs的组成和含量均在不断变化且差异明显。