Detection of milk oligosaccharides in plasma of infants (original) (raw)

A quantitative and comprehensive method to analyze human milk oligosaccharide structures in the urine and feces of infants

Analytical and Bioanalytical Chemistry, 2013

Human milk oligosaccharides (HMOs), though non-nutritive to the infant, shape the intestinal microbiota and protect against pathogens during early growth and development. Infant formulas with added galacto-oligosaccharides have been developed to mimic the beneficial effects of HMOs. Premature infants have an immature immune system and a leaky gut and are thus highly susceptible to opportunistic infections. A method employing nanoflow liquid chromatography time-of-flight mass spectrometry (MS) is presented to simultaneously identify and quantify HMOs in the feces and urine of infants, of which 75 HMOs have previously been fully structurally elucidated. Matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance MS was employed for high-resolution and rapid compositional profiling. To demonstrate this novel method, samples from mother-infant dyads as well as samples from infants receiving infant formula fortified with dietary galacto-oligosaccharides or probiotic bifidobacteria were analyzed. Ingested oligosaccharides are demonstrated in high abundance in the infant feces and urine. While the method was developed to examine specimens from preterm infants, it is of general utility and can be used to monitor oligosaccharide consumption and utilization in term infants, children and adults. This method may therefore provide diagnostic and therapeutic opportunities.

Current Perspective of Sialylated Milk Oligosaccharides in Mammalian Milk: Implications for Brain and Gut Health of Newborns

Foods, 2021

Human milk oligosaccharides (HMOs) are the third most abundant solid component after lactose and lipids of breast milk. All mammal milk contains soluble oligosaccharides, including neutral milk oligosaccharides (NMOs) without sialic acid (Sia) moieties and acidic oligosaccharides or sialylated milk oligosaccharides (SMOs) with Sia residues at the end of sugar chains. The structural, biological diversity, and concentration of milk oligosaccharides in mammalian milk are significantly different among species. HMOs have multiple health benefits for newborns, including development of immune system, modification of the intestinal microbiota, anti-adhesive effect against pathogens, and brain development. Most infant formulas lack oligosaccharides which resemble HMOs. Formula-fed infants perform poorly across physical and psychological wellbeing measures and suffer health disadvantages compared to breast-fed infants due to the differences in the nutritional composition of breast milk and in...

Validation and application of a method for the simultaneous absolute quantification of 16 neutral and acidic human milk oligosaccharides by graphitized carbon liquid chromatography – electrospray ionization – mass spectrometry

Food Chemistry, 2019

Human milk oligosaccharides (HMOs) are free glycans naturally present in human milk that act as prebiotics, prevent pathogen binding, modulate the immune system and support brain development in infants. The HMOs composition and concentrations vary significantly among different women mainly because of the direct influence of the Secretor and Lewis phenotypes on HMOs biosynthesis. Analytical methods that can identify the differences in the HMOs composition and concentrations are a fundamental tool in HMOs research. This paper describes a simple HMOs extraction and analysis for the simultaneous and absolute quantification of neutral and acidic HMOs by graphitized carbon liquid chromatography-electrospray ionization-mass spectrometry. This method was validated and applied to analyze HMOs in the human milk obtained from 10 women. This method allows accurate and reliable quantification of HMOs and can be used to determine differences in HMOs concentrations throughout lactation and among women with different Secretor and Lewis phenotypes.

Oligosaccharides in human milk, achievements in analysis: a review

Research for Rural Development 2022 : annual 28th International scientific conference proceedings

Human milk oligosaccharides (HMOs) comprise about 20% of the total carbohydrates of human milk. There is currently a growing interest in HMOs as many researchers have recognized the importance of their benefits to infant health. Accumulated evidence suggests that HMOs are anti-adhesive antimicrobials that serve as soluble bait receptors, prevent pathogens from attaching to infant mucous membranes, and reduce the risk of viral, bacterial, and protozoan parasites. It also provides functionality including anti-adhesion and immunomodulators. Even though the composition of human milk in Latvia has been studied in detail, there are no studies on oligosaccharides in human milk. The aim of the study is to find out recent advances in the analysis of HMOs. Semi-systematic method was used to analyze the latest information about the recent advances in the analysis of HMOs by liquid phase separation methods, to investigate any known associations between HMOs composition and maternal nutrition an...

Infants Are Exposed to Human Milk Oligosaccharides Already in utero

Frontiers in Pediatrics

Human milk oligosaccharides (HMOs) are complex carbohydrates that are highly abundant in and, in their complexity, unique to human milk. Accumulating evidence indicates that exposure to HMOs in the postnatal period affects immediate as well as long-term infant health and development. However, studies reported in the 1970s showed that HMOs already appear in maternal urine and blood during pregnancy and as early as the first trimester. In this pilot study we aimed to determine whether or not HMOs also appear in amniotic fluid. We enrolled women during pregnancy and collected their urine and amniotic fluid at birth as well as their milk 4 days postpartum. We analyzed the samples by high-performance liquid chromatography (HPLC) and mass spectrometry and identified several HMOs including 2 ′-fucosyllactose, 3-fucosyllactose, difucosyllactose, and 6 ′-sialyllactose to be present in different relative abundancies in all three tissues. This is the first report that HMOs appear in amniotic fluid and that the fetus is already exposed to HMOs in utero, warranting future research to investigate the immediate and long-term implications on fetal and infant health and development.

13C-labeled oligosaccharides in breastfed infants' urine: Individual-, structure- and time-dependent differences in the excretion

Glycobiology, 2013

Human milk oligosaccharides (HMOs) have been paid much attention due to their beneficial effects observed in vitro, e.g., prebiotic, anti-infective and anti-inflammatory properties. However, in vivo investigations with regard to HMO metabolism and functions are rare. The few data available indicate that HMOs are absorbed to a low extent and excreted via urine without noteworthy modifications, whereas the major proportion reaches infant's colon undigested. Via intrinsic 13 C-labeling of HMOs during their biosynthesis in the mammary gland of 10 lactating women, we were able to follow the fate of 13 C-labeled oligosaccharides (OSs) from their secretion in milk to the excretion in the urine of their breastfed infants. To a certain extent, we could therefore discriminate between original HMOs and non-labeled OSs derived from degradation of HMOs or endogenous glycoconjugates. By means of our novel, rapid, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based approach, we found a homogeneous time pattern of isotopomer enrichment in milk among all subjects and between single OS species. In contrast, the time curves from infants' urine varied strongly between individuals and OS species, though the overall MALDI-TOF MS profile resembled those of the mothers' milk. Our data suggest that neutral HMOs might be processed and/or utilized differentially after or upon absorption from the gut, as deduced from their structure-dependent variation in the extent of tracer enrichment and in the retention times in infant's organism. This sheds new light on the role of HMOs within infant's body, beyond the intestine and its microbiota alone.

Human Milk Oligosaccharides in the Milk of Mothers Delivering Term versus Preterm Infants

Nutrients

Human milk oligosaccharides (HMOs) are a major component of human milk, and play an important role in protecting the infant from infections. Preterm infants are particularly vulnerable, but have improved outcomes if fed with human milk. This study aimed to determine if the HMO composition of preterm milk differed from that of term milk at equivalent stage of lactation and equivalent postmenstrual age. In all, 22 HMOs were analyzed in 500 samples of milk from 25 mothers breastfeeding very preterm infants (< 32 weeks of gestational age, < 1500g of birthweight) and 28 mothers breastfeeding term infants. The concentrations of most HMOs were comparable at equivalent postpartum age. However, HMOs containing α-1,2-linked fucose were reduced in concentration in preterm milk during the first month of lactation. The concentrations of a number of sialylated oligosaccharides were also different in preterm milk, in particular 3′-sialyllactose concentrations were elevated. At equivalent pos...

Challenges and Pitfalls in Human Milk Oligosaccharide Analysis

Nutrients

Human milk oligosaccharides have been recognized as an important, functional biomolecule in mothers’ milk. Moreover, these oligosaccharides have been recognized as the third most abundant component of human milk, ranging from 10–15 g/L in mature milk and up to and over 20 g/L reported in colostrum. Initially, health benefits of human milk oligosaccharides were assigned via observational studies on the differences between breastfed and bottle fed infants. Later, pools of milk oligosaccharides were isolated and used in functional studies and in recent years more specific studies into structure–function relationships have identified some advanced roles for milk oligosaccharides in the healthy development of infants. In other research, the levels, diversity, and complexity of human milk oligosaccharides have been studied, showing a wide variation in results. This review gives a critical overview of challenges in the analysis of human milk oligosaccharides. In view of the myriad function...

Cow Milk Oligosaccharides and Their Relevance to Infant Nutrition

Biology and Life Sciences Forum, 2013

Cow milk oligosaccharides (CMOs) are complex carbohydrates found in cow milk that resemble the oligosaccharides in human milk and are essential for regulating the immune system and forming the gut flora of infants. As prebiotics, they promote the growth of specific beneficial gut bacteria, such as Lactobacilli and Bifidobacteria, thus promoting the creation of short-chain fatty acids for gut health. Furthermore, CMOs correlate with enhanced infant immune system development, offering safeguards against pathogens and anti-inflammatory benefits. The results of recent CMO research are revealed in this review, together with their biological importance and potential applications. Their relevance to infant nutrition is highlighted, as is their potential to be used as bioactive ingredients in novel functional foods and nutraceuticals. This study also describes upcoming obstacles and opportunities for CMO research, such as understanding their structures and functions, improving extraction methods, and expanding applications to different age groups. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

CE‐LIF‐MS n profiling of oligosaccharides in human milk and feces of breast‐fed babies

ELECTROPHORESIS, 2010

Mixtures of the complex human milk oligosaccharides (HMOs) are difficult to analyze and gastrointestinal bioconversion products of HMOs may complicate analysis even more. Their analysis, therefore, requires the combination of a sensitive and high-resolution separation technique with a mass identification tool. This study introduces for the first time the hyphenation of CE with an electrospray mass spectrometer, capable to perform multiple MS analysis (ESI-MS n) for the separation and characterization of HMOs in breast milk and feces of breast-fed babies. LIF was used for on-and off-line detections. From the overall 47 peaks detected in off-line CE-LIF electropherograms, 21 peaks could be unambiguously and 11 peaks could be tentatively assigned. The detailed structural characterization of a novel lacto-N-neo-tetraose isomer and a novel lacto-Nfucopentaose isomer was established in baby feces and pointed to gastrointestinal hydrolysis of higher-Mw HMOs. CE-LIF-ESI-MS n presents, therefore, a useful tool which contributes to an advanced understanding on the fate of individual HMOs during their gastrointestinal passage.