Human milk oligosaccharide 2’-fucosyllactose links feedings at 1 month to cognitive development at 24 months in infants of normal and overweight mothers

Berger, Paige K.; Plows, Jasmine F.; Jones, Roshonda B.; Alderete, Tanya L.; Yonemitsu, Chloe; Poulsen, Marie Kanne; Ryoo, Ji Hoon; Peterson, Bradley S.; Bode, Lars; Goran, Michael I.

doi:10.1371/journal.pone.0228323

Cited by 102 publications

(133 citation statements)

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“…In Finland, 2′FL was positively associated with change in length, but not weight, from 3 to 12 mo ( 17 ), whereas in Denmark 2′FL was positively associated with weight gain from 0 to 5 mo, but not length ( 18 ). In Los Angeles, 2′FL at 1 mo (but not at 6 mo) was positively associated with cognitive development at 24 mo in 50 mother-child dyads ( 20 ). In both Finland and Denmark, LNnT was inversely associated with length and weight ( 17 , 18 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, there is limited evidence of associations of HMOs with infant growth and development in lower-income countries, and we could find no evidence of associations of bioactive proteins with infant growth and development. Studies in Finland ( 17 ), Denmark ( 18 ), and the United States ( 19 ) demonstrated that 2′-fucosyllactose (2′FL) was positively associated and lacto- N -neotetraose (LNnT) and lacto- N -fucopentaose I (LNFP I) were inversely associated with child height and weight, whereas 2′FL at 1 mo was positively associated with infant cognitive development at 24 mo among infants in the United States ( 20 ). The authors of those articles speculate that the HMOs affect infant growth via modulation of the infants’ intestinal microbiota.…”

Section: Introductionmentioning

confidence: 99%

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Associations of human milk oligosaccharides and bioactive proteins with infant growth and development among Malawian mother-infant dyads

Jorgensen

Young

Ashorn

et al. 2021

The American Journal of Clinical Nutrition

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Background Human milk oligosaccharides (HMOs) and bioactive breast milk proteins have many beneficial properties. Information is sparse regarding associations between these milk constituents and infant growth and development in lower-income countries. Objectives We aimed to examine associations of milk content of HMOs and bioactive proteins at 6 mo postpartum with infant growth and motor and cognitive development. These are secondary analyses of a randomized controlled trial in rural Malawi. Methods Breast milk samples were analyzed at 6 mo (n = 659) for general categories of HMOs (total HMOs, fucosylated HMOs, and sialylated HMOs), 51 individual HMOs, and 6 bioactive proteins (lactalbumin, lactoferrin, lysozyme, antitrypsin, IgA, and osteopontin). We examined associations of the relative abundances of HMOs and concentrations of bioactive proteins with infant growth from 6 to 12 mo [change in length-for-age (ΔLAZ), weight-for-age, weight-for-length, and head circumference z-scores] as well as ability to stand or walk alone at 12 mo, and motor and language skills, socioemotional development, executive function, and working memory at 18 mo. Analyses were adjusted for covariates and multiple hypothesis testing. Results Among all participants, there were inverse associations of IgA and lactoferrin concentrations with motor skills (P = 0.018 and P = 0.044), and a positive association of lactalbumin concentration with motor skills (P = 0.038). Among secretors only [fucosyltransferase 2 gene (FUT2) positive], there were positive associations of absolute abundance of HMOs with ΔLAZ (P = 0.035), and relative abundance of fucosylated and sialylated HMOs with language at 18 mo (P < 0.001 and P = 0.033, respectively), and inverse associations of osteopontin with standing and walking at 12 mo (P = 0.007 and 0.002, respectively). Relative abundances of several individual HMOs were associated with growth and development, mostly among secretors. Conclusions Certain bioactive breast milk proteins and HMOs are associated with infant growth and motor and cognitive development. Further studies are needed to determine if a causal relation exists. This trial was registered at clinicaltrials.gov as NCT01239693.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Associations of human milk oligosaccharides and bioactive proteins with infant growth and development among Malawian mother-infant dyads

Jorgensen

Young

Ashorn

et al. 2021

The American Journal of Clinical Nutrition

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“…HMOs are major bioactive components of human milk and provide a number of advantages to infant health [1,30,31]. However, not all HMOs are created equal, when it comes to possessing beneficial and protective properties for the infant gut.…”

Section: Discussionmentioning

confidence: 99%

Third-Trimester Glucose Homeostasis in Healthy Women Is Differentially Associated with Human Milk Oligosaccharide Composition at 2 Months Postpartum by Secretor Phenotype

et al. 2020

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Human milk oligosaccharides (HMOs) are bioactive molecules in human milk that play a critical role in infant health. Obesity and associated metabolic aberrations can negatively impact lactation and alter milk composition. Here, the relationship between maternal glucose homeostasis and HMO composition from 136 healthy women was examined. Maternal glucose homeostasis (fasting plasma glucose and insulin, homeostatic model assessment for insulin resistance, and insulin sensitivity index) was evaluated at 30 weeks of gestation in healthy women (body mass index = 18.5–35 kg/m2). Human milk samples were collected at two months postpartum. HMO concentrations were measured via high performance liquid chromatography. Women were categorized into “secretor” and “non-secretor” groups based on 2′-Fucosyllactose concentrations (<100 nmol/mL, non-secretor). Pearson’s correlation analysis and linear models were used to assess the relationships between maternal glucose homeostasis and HMO concentrations. In non-secretors, third trimester fasting plasma glucose and insulin were negatively associated with total HMO-bound sialic acid and concentrations of the sialylated HMOs 3′-sialyllactose and disialylacto-N-tetraose. In secretors, difucosyllactose and lacto-N-fucopentaose-II concentrations increased and sialyllacto-N-tetraose c and sialyllacto-N-tetraose b decreased as insulin sensitivity increased. This study is the first to demonstrate a relationship between obesity-associated maternal factors and HMO composition in both secretor and non-secretor populations.

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“…The latest research of mother-infant pairs suggested that the frequency of breastfeeding at 1 month due to the higher exposure to mother's milk 2 -FL promotes cognitive development of newborns, evaluated at 24 months with the Bayley-III Scale [132]. However, the same effect was not observed for 6-month-old newborns.…”

Section: Dietary Fucosylated Hmos As a Substrate For Synthesis Of Newmentioning

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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Human milk oligosaccharide 2’-fucosyllactose links feedings at 1 month to cognitive development at 24 months in infants of normal and overweight mothers

Cited by 102 publications

References 43 publications

Associations of human milk oligosaccharides and bioactive proteins with infant growth and development among Malawian mother-infant dyads

Associations of human milk oligosaccharides and bioactive proteins with infant growth and development among Malawian mother-infant dyads

Third-Trimester Glucose Homeostasis in Healthy Women Is Differentially Associated with Human Milk Oligosaccharide Composition at 2 Months Postpartum by Secretor Phenotype

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

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