Dataset Information

Time of Lactation and Maternal Fucosyltransferase Genetic Polymorphisms Determine the Variability in Human Milk Oligosaccharides.

ABSTRACT: Rationale: Human milk oligosaccharides (HMOs) vary among mothers and genetic factors contribute to this variability. We assessed changes in HMO concentrations during the first year of lactation and the relationship with FUT2 Secretor group and FUT3 Lewis group defining genetic polymorphisms. Methods: Milk samples were collected from lactating mothers participating in the LIFE Child cohort in Leipzig, Germany. The concentrations of 24 HMOs in milk samples collected at 3 months (N = 156), 6 months (N = 122), and 12 months (N = 28) were measured using liquid chromatography. Concentrations of HMOs were compared at all time-points and were tested for their associations with FUT2 and FUT3 genetic variations by sPLS regression. Results: FUT2 SNP rs601338 was found to predominantly define the Secretor status Se-: 11.8% and it was highly correlated with 2'-fucosyllactose (2'FL, p < 0.001) and lacto-N-fucosylpentaose-I (LNFP-I, p < 0.001). FUT3 SNPs rs28362459 and rs812936 were found to define Lewis status (Le-: 5.9%) and correlated with lacto-N-fucosylpentaose-II (LNFP-II, p < 0.001). A polygenic score predicted the abundance of 2'FL levels within Secretors' milk (adj. R 2 = 0.58, p < 0.001). Mean concentrations of most of the individual HMOs, as well as the sums of the measured HMOs, the fucosylated HMOs, and the neutral HMOs were lower at 6 and 12 months compared to 3 months (p < 0.001). Conclusions: Secretor and Lewis status defined by specific FUT2 and FUT3 SNPs are confirmed to be good proxies for specific individual HMOs and milk group variabilities. The polygenic score developed here is an opportunity for clinicians to predict 2'FL levels in milk of future mothers. These results show opportunities to strengthen our understanding of factors controlling FUT2 and FUT3 functionality, the temporal changes and variability of HMO composition during lactation and eventually their significance for infant development.

SUBMITTER: Lefebvre G

PROVIDER: S-EPMC7658960 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Time of Lactation and Maternal Fucosyltransferase Genetic Polymorphisms Determine the Variability in Human Milk Oligosaccharides.

Lefebvre Gregory G Shevlyakova Maya M Charpagne Aline A Marquis Julien J Vogel Mandy M Kirsten Toralf T Kiess Wieland W Austin Sean S Sprenger Norbert N Binia Aristea A

Frontiers in nutrition 20201029

Rationale: Human milk oligosaccharides (HMOs) vary among mothers and genetic factors contribute to this variability. We assessed changes in HMO concentrations during the first year of lactation and the relationship with FUT2 Secretor group and FUT3 Lewis group defining genetic polymorphisms. Methods: Milk samples were collected from lactating mothers participating in the LIFE Child cohort in Leipzig, Germany. The concentrations of 24 HMOs in milk samples collected at ...[more]

PMID: 33195368

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Project description:The quantitation of human milk oligosaccharides (HMOs) is challenging because of the structural complexity and lack of standards.The objective of our study was to rapidly measure the absolute concentrations of HMOs in milk using LC-mass spectrometry (MS) and to determine the phenotypic secretor status of the mothers.This quantitative method for measuring HMO concentration was developed by using ultraperformance LC multiple reaction monitoring MS. It was validated and applied to milk samples from Malawi (88 individuals; 88 samples from postnatal month 6) and the United States (Davis, California; 45 individuals, mean age: 32 y; 103 samples collected on postnatal days 10, 26, 71, or 120, repeated measures included). The concentrations of ?(1,2)-fucosylated HMOs were used to determine the mothers' phenotypic secretor status with high sensitivity and specificity. We used Friedman's test and Wilcoxon's signed rank test to evaluate the change in HMO concentration during the course of lactation, and Student's t test was used to compare secretors and nonsecretors.A decrease (P < 0.05) in HMO concentration was observed during the course of lactation for the US mothers, corresponding to 19.3 ± 2.9 g/L for milk collected on postnatal day 10, decreasing to 8.53 ± 1.18 g/L on day 120 (repeated measures; n = 14). On postnatal day 180, the total concentration of HMOs in Malawi milk samples from secretors (6.46 ± 1.74 mg/mL) was higher (P < 0.05) than that in samples from nonsecretors (5.25 ± 2.55 mg/mL ). The same trend was observed for fucosylated species; the concentration was higher in Malawi milk samples from secretors (4.91 ± 1.22 mg/mL) than from nonsecretors (3.42 ± 2.27 mg/mL) (P < 0.05).HMOs significantly decrease during the course of lactation. Secretor milk contains higher concentrations of total and fucosylated HMOs than does nonsecretor milk. These HMO concentrations can be correlated to the health of breastfed infants in order to investigate the protective effects of milk components. The trials were registered at clinicaltrials.gov as NCT01817127 and NCT00524446.

Project description:BackgroundHuman 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.ObjectivesThe purpose of this study is to investigate factors associated with HMO concentrations in Chinese populations.MethodsA 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.ResultsMedian 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).ConclusionsThe 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).

Project description:The composition of porcine milk oligosaccharides (PMO) was analyzed during early lactation and their relation to piglet gut microbiome was investigated. Pigs are considered ideal intestinal models to simulate humans because of the striking similarity in intestinal physiopathology to humans. The evolution of PMO was investigated in the milk from 3 healthy sows at prefarrowing, farrowing, and d 7 and 14 postpartum by Nano-LC Chip Quadrupole-Time-of-Flight mass spectrometer (Agilent Technologies, Santa Clara, CA). Previously sequenced metagenome libraries were reanalyzed to examine changes with specific gut bacterial populations. Over 30 oligosaccharides (OS) were identified in the milk, with 3'-sialyllactose, lacto-N-tetraose, α1-3,β1-4-d-galactotriose, 2'-fucosyllactose, and 6'-sialyllactose being the most abundant species (accounting for ~70% of the total OS). Porcine milk had lower OS diversity (number of unique structures) than human milk, and appeared closer to bovine and caprine milk. In agreement with previous studies, only 3 fucosylated OS were identified. Surprisingly, their contribution to total OS abundance was greater than in bovine milk (9 vs. 1%). Indeed, fucosylated PMO increased during lactation, mirroring a similar trend observed for neutral and type I OS content during early lactation. Taken together, these results suggest that, in terms of abundance, PMO are closer to human milk than other domestic species, such as bovine and caprine milks. Metagenomic sequencing revealed that fucose-consuming bacterial taxa in the gut microbiota of piglets were qualitatively but not quantitatively different between nursing and weaning stages, suggesting that both the composition and structure of dietary glycans may play a critical role in shaping the distal gut microbiome. The similarity of both intestinal physiopathology and milk OS composition in human and porcine species suggests similar effects on gastrointestinal development of early nutrition, reinforcing the use of the pig intestinal model to simulate human intestinal models in the clinical setting.

Dataset Information

Time of Lactation and Maternal Fucosyltransferase Genetic Polymorphisms Determine the Variability in Human Milk Oligosaccharides.

Publications

Time of Lactation and Maternal Fucosyltransferase Genetic Polymorphisms Determine the Variability in Human Milk Oligosaccharides.

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