Fucosylated Human Milk Oligosaccharides and N-Glycans in the Milk of Chinese Mothers Regulate the Gut Microbiome of Their Breast-Fed Infants during Different Lactation Stages

Bai, Yaqiang; Tao, Jia; Zhou, Jiaorui; Fan, Q; Liu, Man; Hu, Yuqi; Yao, Xu; Zhang, Lilong; Yuan, Jieli; Li, Wenzhe; Ze, Xiaolei; Malard, Patrice; Guo, Zhimou; Yan, Jingyu; Li, Ming

doi:10.1128/msystems.00206-18

Cited by 85 publications

(117 citation statements)

References 78 publications

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“…Nevertheless, these HMOs deeply decreased at 6 months. One study revealed that fucosylated HMOs could regulate the gut microbiome of infants during different lactation stages [27]. We believe that infants need to be exposed to a certain content of HMOs at specific stages of their development, and different pathways of HMOs exert different roles during different stages.…”

Section: Hmos Concentration During Lactationmentioning

confidence: 97%

“…However, most studies collected samples in a single time point or focused on first few weeks of lactation. In addition, HMOs vary during lactation and may also be influenced by the gestational stage [17,27]. Recently, researchers found that HMOs composition and concentration presented a wide variability in women with the same genetic background [28], which suggested that sociodemographic and environmental factors may play a role.…”

Section: Introductionmentioning

confidence: 99%

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Neutral Human Milk Oligosaccharides Are Associated with Multiple Fixed and Modifiable Maternal and Infant Characteristics

Wang

Zhao

et al. 2020

Nutrients

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We aimed to identify if maternal and infant factors were associated with neutral human milk oligosaccharides (HMOs) variability and examined the associations between HMOs concentration and infant growth and disease status in healthy Chinese mothers over a 6-month lactation period. We recruited mothers and their full-term infants as our subjects. At 1–5 days, 8–14 days, 4 weeks, and 6 months postpartum, all participants were interviewed to collect breast milk samples, obtain follow-up data and measure infant length and weight at their local hospital. A total of 23 neutral HMOs were analyzed by high performance liquid chromatography (HPLC)- mass spectrometer (MS). Secretor and Lewis phenotype were determined by the concentration of 2′-fucosyllactose (2′-FL) and Lacto-N-fucopentaose (LNFP)-II. The associations between maternal and infant factors with HMOs concentrations were investigated. A total of 464 human breast milk samples were collected from 116 mothers at four different time points. In total, 76.7% mothers were found to be Secretor and Lewis positive phenotype (Se+Le+), 17.2% were Se-Le+, 4.3% were Se+Le-, and 1.7% were Se-Le-. Several individual HMOs, including 2′-FL, Lactodifucotetraose (LDFT), LNFP-I were determined by Secretor phenotype. Most individual HMOs decreased at the later stage of lactation, except 3′-FL. We suggest that Secretor phenotype and lactation stage could influence most of the neutral HMOs. Concentrations of specific HMOs may be associated with maternal age, allergic history, pre-pregnancy body mass index (BMI), parity, delivery mode, infant gestational age and gender.

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Section: Hmos Concentration During Lactationmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Neutral Human Milk Oligosaccharides Are Associated with Multiple Fixed and Modifiable Maternal and Infant Characteristics

Wang

Zhao

et al. 2020

Nutrients

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“…15,16 Among the complex N-glycans, we noticed that the glycans carrying one fucose gradually decreased, while those harboring multiple fucose moieties increased in time from early to mature lactation, again consistent with previous findings based on studies focused on released N-glycans. 22 Having established a global picture of the glycan distribution as occurring on glycoproteins in human milk, we used these data to make a rough comparison to the global distribution of glycans in human serum, taking serum data reported earlier 23 ( Figure S2). This comparison revealed, not surprisingly, that global glycoproteome compositions in human milk and serum are quite distinct.…”

Section: Journal Of Proteome Research Pubsacsorg/jpr Articlementioning

confidence: 99%

Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor Reveals the Highly Variable Repertoire and Dynamic Site-Specific Changes

et al. 2020

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Protein N-glycosylation on human milk proteins assists in protecting an infant's health and functions among others as competitive inhibitors of pathogen binding and immunomodulators. Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein-and N-site-specific quantitative information. Here, we describe an automated platform using hydrophilic-interaction chromatography (HILIC)-based cartridges enabling the proteome-wide monitoring of intact Nglycopeptides using just a digest of 150 μg of breast milk protein. We were able to map around 1700 glycopeptides from 110 glycoproteins covering 191 glycosites, of which 43 sites have not been previously reported with experimental evidence. We next quantified 287 of these glycopeptides originating from 50 glycoproteins using a targeted proteomics approach. Although each glycoprotein, N-glycosylation site, and attached glycan revealed distinct dynamic changes, we did observe a few general trends. For instance, fucosylation, especially terminal fucosylation, increased across the lactation period. Building on the improved glycoproteomics approach outlined above, future studies are warranted to reveal the potential impact of the observed glycosylation microheterogeneity on the healthy development of infants.

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“…However, the question concerning which transferases contribute to HMO sialylation remains unanswered. Interestingly, the obtained structures, despite the small structural differences, namely the position of the glycosidic bond with identical qualitative composition for fucosyllactose and sialyllactose, respectively (Figure 1a), show significant functional differences in shaping the gut microbiome and in different levels of protection against fucose-or sialic acid-dependent pathogens, among others [19,32,[38][39][40][41][42][43]. The actions of different fucosyltransferases and sialyltransferases allow the identification of over 100 different oligosaccharide structures [21] Depending on the presence of fucose and sialic acid in the oligosaccharide structure, HMOs are divided as follows: fucosylated (neutral) and non-fucosylated (neutral) oligosaccharides and sialylated (acidic) and non-sialylated molecules, respectively.…”

Section: Structures and Diversity Of Hmosmentioning

confidence: 99%

“…Concentration and mutual proportions of HMOs are affected mainly by 3 different factors, namely polymorphisms of two fucosyltransferase genes (FUT2 and FUT3), which gives 4 different groups of mothers [20,45], stage of milk maturation [40,46] and the week of delivery [47,48]. [49][50][51].…”

Section: Structures and Diversity Of Hmosmentioning

confidence: 99%

The Impact of Dietary Fucosylated Oligosaccharides and Glycoproteins of Human Milk on Infant Well-Being

Orczyk-Pawiłowicz

Lis-Kuberka

2020

Nutrients

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Apart from optimal nutritional value, human milk is the feeding strategy to support the immature immunological system of developing newborns and infants. The most beneficial dietary carbohydrate components of breast milk are human milk oligosaccharides (HMOs) and glycoproteins (HMGs), involved in both specific and nonspecific immunity. Fucosylated oligosaccharides represent the largest fraction of human milk oligosaccharides, with the simplest and the most abundant being 2′-fucosyllactose (2′-FL). Fucosylated oligosaccharides, as well as glycans of glycoproteins, as beneficial dietary sugars, elicit anti-adhesive properties against fucose-dependent pathogens, and on the other hand are crucial for growth and metabolism of beneficial bacteria, and in this aspect participate in shaping a healthy microbiome. Well-documented secretor status related differences in the fucosylation profile of HMOs and HMGs may play a key but underestimated role in assessment of susceptibility to fucose-dependent pathogen infections, with a potential impact on applied clinical procedures. Nevertheless, due to genetic factors, about 20% of mothers do not provide their infants with beneficial dietary carbohydrates such as 2′-FL and other α1,2-fucosylated oligosaccharides and glycans of glycoproteins, despite breastfeeding them. The lack of such structures may have important implications for a wide range of aspects of infant well-being and healthcare. In light of the above, some artificial mixtures used in infant nutrition are supplemented with 2′-FL to more closely approximate the unique composition of maternal milk, including dietary-derived fucosylated oligosaccharides and glycoproteins.

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Fucosylated Human Milk Oligosaccharides and N-Glycans in the Milk of Chinese Mothers Regulate the Gut Microbiome of Their Breast-Fed Infants during Different Lactation Stages

Cited by 85 publications

References 78 publications

Neutral Human Milk Oligosaccharides Are Associated with Multiple Fixed and Modifiable Maternal and Infant Characteristics

Neutral Human Milk Oligosaccharides Are Associated with Multiple Fixed and Modifiable Maternal and Infant Characteristics

Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor Reveals the Highly Variable Repertoire and Dynamic Site-Specific Changes

The Impact of Dietary Fucosylated Oligosaccharides and Glycoproteins of Human Milk on Infant Well-Being

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