Development of high-throughput UPLC-MS/MS using multiple reaction monitoring for quantitation of complex human milk oligosaccharides and application to large population survey of secretor status and Lewis blood group

Li, Jiaqi; Bi, Yang; Zheng, Yi; Cao, Cuiyan; Yu, Long; Yang, Zhenyu; Chai, Wengang; Yan, Jingyu; Lai, Jianqiang; Liang, Xinmiao

doi:10.1016/j.foodchem.2022.133750

Cited by 17 publications

(18 citation statements)

References 45 publications

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“…McGuire et al [ 1 ] suggested normal HMO concentrations and profiles vary geographically. Li et al [ 26 ] indicated that HMO concentration of the Tibetans was 56% higher than the concentration of Zhuang, and the concentration of Han (6.3 g/L) was close to the average value (5.6 g/L) of all samples, which was within the scope of our research results. This result is the average of all data during different lactation periods (colostrum, transitional, and mature milk), with a mean lactation value of 143 days, with the earliest at day 6 and the longest at day 347.…”

Section: Discussionsupporting

confidence: 85%

“…Human milk oligosaccharide (HMO) content was determined using a recently published high-throughput UPLC-MRM method [ 26 ]. An ACQUITY Ultraperformance system (Waters, Milford, MA, USA) coupled to a Xevo TQ-XS triple quadrupole mass spectrometer (Waters) was used for analysis.…”

Section: Methodsmentioning

confidence: 99%

“…The subjects’ secretor status and Lewis blood type was determined by the presence of specific oligosaccharide and ion fragments. The presence of the product ion m / z 325 from 2′-fucosyllactose (2′-FL), Lactodifucotetraose (LDFT), lacto- N -fucopentaose I (LNFP-I), and lacto- N -neo-difucohexaose I (LNnDFH-I) can be used as an indicator of secretor’s status, while lacto- N -fucopentaose II (LNFP-II) with the fragment ion m / z 348 can be used as an indicator of Lewis blood-group phenotype [ 26 , 27 ]. Study sites were divided into rural and urban areas or were classified into coastal and inland areas based on geographic features.…”

Section: Methodsmentioning

confidence: 99%

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Human Milk Oligosaccharides Are Associated with Lactation Stage and Lewis Phenotype in a Chinese Population

Ren

Yan

et al. 2023

Nutrients

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Background: Human milk oligosaccharides (HMOs) are the third most abundant component of human milk. Various factors may affect the concentration of HMOs, such as the lactation period, Lewis blood type, and the maternal secretor gene status. Objectives: The purpose of this study is to investigate factors associated with HMO concentrations in Chinese populations. Methods: A sub-sample of 481 was randomly selected from a large cross-sectional study in China (n = 6481) conducted in eight provinces (Beijing, Heilongjiang, Shanghai, Yunnan, Gansu, Guangdong, Zhejiang, and Shandong) between 2011 and 2013. HMO concentrations were determined by a high-throughput UPLC-MRM method. Various factors were collected through face-to-face interviews. Anthropometric measurement was conducted by trained staff. Results: Median total HMO concentration was 13.6 g/L, 10.7 g/L, and 6.0 g/L for colostrum, transitional milk, and mature milk, respectively. HMO concentration decreased significantly as the lactation period increased (p < 0.0001). There were significant differences of average total HMO concentration between secretor mothers and non-secretor mothers (secretor 11.3 g/L vs. non-secretor 5.8 g/L, p < 0.0001). There were significant differences of average total HMO concentrations among three Lewis blood types (p = 0.003). Comparing with the concentration of total oligosaccharides of Le+ (a−b+), average of total oligosaccharides concentrations increased by 3.9 (Le+ (a+b−), p = 0.004) and 1.1 g/L (Le− (a−b−), p = 0.049). The volume of breast milk expressed and the province the mother came from affected the concentration of total oligosaccharides (all p < 0.0001). Maternal BMI (p = 0.151), age (p = 0.630), prematurity (p = 0.850), mode of delivery (p = 0.486), infants’ gender (p = 0.685), maternal education level (p = 0.989), maternal occupation (p = 0.568), maternal allergic history (p = 0.370), maternal anemia (p = 0.625), pregnancy-induced hypertension (p = 0.739), gestational diabetes (p = 0.514), and parity (p = 0.098) were not significantly correlated with the concentration of milk oligosaccharides. The concentrations of 2′-fucosyllactose (2′-FL), lacto-N-neotetraose (LNnT), sialyllacto-N-tetraose c (LSTc), lacto-N-fucopentaose I (LNFP-I), disialylated lacto-N-tetraose (DSLNT), difucosyl-para-lacto-N-neohexaose (DFpLNnH), difucosyl-lacto-N-hexaose (DFLNH[a]), and 3-sialyllactose (3′-SL) showed a gradual downward trend, while the concentration of 3-fucosyllactose (3-FL) showed a gradual upward trend among three lactation stages (p < 0.05). Conclusions: The concentration of HMOs changes throughout lactation, and it varies between different HMOs. HMO concentrations differed between lactation stage, maternal secretor gene status, Lewis blood type, volume of breast milk expressed, and the province the mother came from. Prematurity, mode of delivery, parity, infants’ gender, and maternal characteristics did not affect the HMO concentration. Geographical region may be not associated with HMOs concentration in human milk. There may be a mechanism for co-regulation of the secretion of some of the oligosaccharides such as 2′FL vs. 3FL, 2′FL vs. LNnT, and lacto-N-tetraose (LNT).

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Section: Discussionsupporting

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Human Milk Oligosaccharides Are Associated with Lactation Stage and Lewis Phenotype in a Chinese Population

Ren

Yan

et al. 2023

Nutrients

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“…Human and bovine milk samples, each with a volume of about 20 L, were employed by the laboratory of the Dalian Institute of Chemical Physics (Chinese Academy of Sciences, Dalian, China) to obtain the milk oligosaccharide fractions used in the current study. The whole isolation-separation process was carried out in accordance with Li et al [ 66 ]. Briefly, both milk samples, initially stored at −40 °C, were first thawed at 4 °C and then filtered using a 750 KDa and a 50 KDa hollow fiber membranes (Shandong Bona Biology, Shandong, China) to remove most of the lipids and proteins.…”

Section: Methodsmentioning

confidence: 99%

Short-Term Effects of Human versus Bovine Sialylated Milk Oligosaccharide Microinjection on Zebrafish Larvae Survival, Locomotor Behavior and Gene Expression

Licitra

Naef

Marchese

et al. 2023

IJMS

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Milk oligosaccharides are a complex class of carbohydrates that act as bioactive factors in numerous defensive and physiological functions, including brain development. Early nutrition can modulate nervous system development and can lead to epigenetic imprinting. We attempted to increase the sialylated oligosaccharide content of zebrafish yolk reserves, with the aim of evaluating any short-term effects of the treatment on mortality, locomotor behavior, and gene expression. Wild-type embryos were microinjected with saline solution or solutions containing sialylated milk oligosaccharides extracted from human and bovine milk. The results suggest that burst activity and larval survival rates were unaffected by the treatments. Locomotion parameters were found to be similar during the light phase between control and treated larvae; in the dark, however, milk oligosaccharide-treated larvae showed increased test plate exploration. Thigmotaxis results did not reveal significant differences in either the light or the dark conditions. The RNA-seq analysis indicated that both treatments exert an antioxidant effect in developing fish. Moreover, sialylated human milk oligosaccharides seemed to increase the expression of genes related to cell cycle control and chromosomal replication, while bovine-derived oligosaccharides caused an increase in the expression of genes involved in synaptogenesis and neuronal signaling. These data shed some light on this poorly explored research field, showing that both human and bovine oligosaccharides support brain proliferation and maturation.

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“…The extraction and fractionation of HMOs were performed as previously reported and neutral fraction DP4 to DP10 were obtained. 17 The DP7 fraction was further separated by PGC columns (Hypercarb, 5 μm, Thermo Fisher Scientific, Waltham, MA) to obtain isomeric heptasaccharides by acetonitrile/water gradient elution at a flow rate of 0.8 mL/min for preparative (4.6 × 150 mm) and 0.2 mL/min for analytical scale (2.1 × 100 mm) separation.…”

Section: Methodsmentioning

confidence: 99%

GIPS-Mix for Accurate Identification of Isomeric Components in Glycan Mixtures Using Intelligent Group-Opting Strategy

et al. 2022

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Accurate identification of glycan structures is highly desirable as they are intimately linked to their different functions. However, glycan samples generally exist as mixtures with multiple isomeric structures, making assignment of individual glycan components very challenging, even with the aid of multistage mass spectrometry (MS n ). Here, we present an approach, GIPS-mix, for assignment of isomeric glycans within a mixture using an intelligent group-opting strategy. Our approach enumerates all possible combinations (groupings) of candidate glycans and opts in the best-matched glycan group(s) based on the similarity between the simulated spectra of each glycan group and the acquired experimental spectra of the mixture. In the case that a single group could not be elected, a tie break is performed by additional MS n scanning using intelligently selected precursors. With 11 standard mixtures and 6 human milk oligosaccharide fractions, we demonstrate the application of GIPS-mix in assignment of individual glycans in mixtures with high accuracy and efficiency.

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Development of high-throughput UPLC-MS/MS using multiple reaction monitoring for quantitation of complex human milk oligosaccharides and application to large population survey of secretor status and Lewis blood group

Cited by 17 publications

References 45 publications

Human Milk Oligosaccharides Are Associated with Lactation Stage and Lewis Phenotype in a Chinese Population

Human Milk Oligosaccharides Are Associated with Lactation Stage and Lewis Phenotype in a Chinese Population

Short-Term Effects of Human versus Bovine Sialylated Milk Oligosaccharide Microinjection on Zebrafish Larvae Survival, Locomotor Behavior and Gene Expression

GIPS-Mix for Accurate Identification of Isomeric Components in Glycan Mixtures Using Intelligent Group-Opting Strategy

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