Human Milk Oligosaccharides in the Prevention of Necrotizing Enterocolitis: A Journey From in vitro and in vivo Models to Mother-Infant Cohort Studies

Preterm infants who receive human milk instead of formula are 6- to 10-times less likely to develop necrotizing enterocolitis (NEC), one of the most common and devastating intestinal disorders that affects 5–10% of all very-low-birth-weight infants. Combined data from in vitro tissue culture models, in vivo preclinical studies in animal models, as well human mother-infant cohort studies support the hypothesis that human milk oligosaccharides (HMOs), complex sugars that are highly abundant in human milk but not in infant formula, contribute to the beneficial effects of human milk feeding in reducing NEC. The almost 20-year long journey of testing this hypothesis took an interesting turn during HMO in vivo efficacy testing and structure elucidation, suggesting that the original hypothesis may indeed be correct and specific HMO reduce NEC risk, however, the underlying mechanisms are likely different than originally postulated

Methodology to predict stiffness knock-down in laminates for wind turbine blades with artificial wrinkles

This work presents a methodology to evaluate the effect of wrinkle defects in the stiffness response of laminate characteristic of wind turbine blades. The assessment is carried out through numerical models and experimental tests with coupon specimens embedded with artificial wrinkles. Specimens are manufactured with two types of defects, prone to arising along the manufacturing process of wind turbine blades. Image-based numerical models were built to enclose the actual features of the cross-sectional wrinkling of each defect type. Experimental quasi-static tension and compression tests were performed, where extensometers collect the strain distribution about the wrinkle section as around the flat section of the test specimens. Two-dimensional finite element simulations carried out in Abaqus/Standard captured the stiffness behaviour of the two types of wrinkles. The numerical approach is validated against the quasi-static tests retrieving a fair agreement with experimental data. A significant knock-down in the stiffness response was found due to the wrinkle with larger aspect ratio of amplitude / half-wavelength.</p

Residential green environments are associated with human milk oligosaccharide diversity and composition

Publisher Copyright: © 2023, The Author(s).Increased exposure to greener environments has been suggested to lead to health benefits in children, but the associated mechanisms in early life, particularly via biological mediators such as altered maternal milk composition, remain largely unexplored. We investigated the associations between properties of the mother’s residential green environment, measured as (1) greenness (Normalized Difference Vegetation index, NDVI), (2) Vegetation Cover Diversity (VCDI) and (3) Naturalness Index (NI), and human milk oligosaccharides (HMOs), known for their immune- and microbiota-related health effects on the infant (N = 795 mothers). We show that HMO diversity increases and concentrations of several individual HMOs and HMO groups change with increased VCDI and NI in residential green environments. This suggests that variation in residential green environments may influence the infant via maternal milk through modified HMO composition. The results emphasize the mediating role of breastfeeding between the residential green environments and health in early life.Peer reviewe

Associations between human milk oligosaccharides and growth in infancy and early childhood

Background: Breastfeeding modulates infant growth and protects against the development of obesity. However, whether or not maternal variation in human milk components, such as human milk oligosaccharides (HMOs), is associated with programming of child growth remains unknown.Objective: Our objective was to determine the association between maternal HMO composition and child growth during the first 5 y of life. In addition, the association between maternal prepregnancy BMI and HMO composition was assessed.Methods: Human milk samples from 802 mothers were obtained from a prospective population-based birth cohort study, Steps to healthy development of Children (STEPS), conducted in Turku, Finland. HMO composition in these milk samples was analyzed by HPLC. Child growth data from 3 mo to 5 y were collected from municipal well-baby clinics and linked to maternal HMO composition data to test for associations.Results: Maternal HMO composition 3 mo after delivery was associated with height and weight during the first 5 y of life in children of secretor mothers. Specifically, HMO diversity and the concentration of lacto-N-neo-tetraose (LNnT) were inversely associated and that of 2'-fucosyllactose (2'FL) was directly associated with child height and weight z scores in a model adjusted for maternal prepregnancy BMI, mode of delivery, birthweight z score, sex, and time. Maternal prepregnancy BMI was associated with HMO composition.Conclusions: The association between maternal HMO composition and childhood growth may imply a causal relation, which warrants additional testing in preclinical and clinical studies, especially since 2'FL and LNnT are among the HMOs now being added to infant formula. Furthermore, altered HMO composition may mediate the impact of maternal prepregnancy BMI on childhood obesity, which warrants further investigation to establish the cause-and-effect relation.</p

Breastfeeding and the origins of health: Interdisciplinary perspectives and priorities

Breastfeeding and human milk (HM) are critically important to maternal, infant and population health. This paper summarizes the proceedings of a workshop that convened a multidisciplinary panel of researchers to identify key priorities and anticipated breakthroughs in breastfeeding and HM research, discuss perceived barriers and challenges to achieving these breakthroughs and propose a constructive action plan to maximize the impact of future research in this field. Priority research areas identified were as follows: (1) addressing low breastfeeding rates and inequities using mixed methods, community partnerships and implementation science approaches; (2) improving awareness of evidence-based benefits, challenges and complexities of breastfeeding and HM among health practitioners and the public; (3) identifying differential impacts of alternative modes of HM feeding including expressed/pumped milk, donor milk and shared milk; and (4) developing a mechanistic understanding of the health effects of breastfeeding and the contributors to HM composition and variability. Key barriers and challenges included (1) overcoming methodological limitations of epidemiological breastfeeding research and mechanistic HM research; (2) counteracting ‘breastfeeding denialism’ arising from negative personal breastfeeding experiences; (3) distinguishing and aligning research and advocacy efforts; and (4) managing real and perceived conflicts of interest. To advance research on breastfeeding and HM and maximize the reach and impact of this research, larger investments are needed, interdisciplinary collaboration is essential, and the scientific community must engage families and other stakeholders in research planning and knowledge translation

Interrogation of Milk-Driven Changes to the Proteome of Intestinal Epithelial Cells by Integrated Proteomics and Glycomics

Bovine colostrum is a rich source of bioactive components which are important in the development of the intestine, in stimulating gut structure and function and in preparing the gut surface for subsequent colonization of microbes. What is not clear, however, is how colostrum may affect the repertoire of receptors and membrane proteins of the intestinal surface and the post-translational modifications associated with them. In the present work, we aimed to characterize the surface receptor and glycan profile of human HT-29 intestinal cells after exposure to a bovine colostrum fraction (BCF) by means of proteomic and glycomic analyses. Integration of label-free quantitative proteomic analysis and lectin array profiles confirmed that BCF exposure results in changes in the levels of glycoproteins present at the cell surface and also changes to their glycosylation pattern. This study contributes to our understanding of how milk components may regulate intestinal cells and prime them for bacterial interaction

The Human-Milk Oligosaccharide Profile of Lactating Women in Dhaka, Bangladesh.

BACKGROUND: Human-milk oligosaccharides (HMOs) are an abundant component of human milk that have health-related effects on breastfeeding infants. Since variation in HMO composition can be explained by maternal and environmental factors, understanding the diversity in HMOs across settings and identifying context-specific factors associated with HMO abundances is important. OBJECTIVES: The aim was to describe the HMO profile of Bangladeshi women and to estimate the effect of maternal vitamin D supplementation on HMO composition. METHODS: In a cross-sectional analysis of data and samples from the Maternal Vitamin D for Infant Growth trial in Dhaka, Bangladesh (clinicaltrials.gov; NCT01924013), 192 participants were randomly selected including 96 from each of the placebo and highest-dose vitamin D supplementation groups. In mid-feed breast milk samples collected at a mean (±SD) postpartum age of 93 ± 7 d, absolute and relative abundances of 19 HMOs were analyzed by HPLC. "Secretors" were defined as participants with 2'fucosyllactose concentrations >350 nmol/mL. Associations between HMO concentrations and selected maternal or environmental factors were estimated by multivariable linear regression, adjusting for vitamin D group allocation and secretor status. HMO profiles of Bangladeshi women were compared with data from other international cohorts. RESULTS: Overall, 34% (65/192) of participants were nonsecretors. Secretor status was associated with the concentrations of total HMOs and 79% (15/19) of individual HMOs. Vitamin D supplementation did not affect the total or individual concentration of any measured HMO. 3-Fucosyllactose concentration was significantly higher in breast milk samples collected in December to February compared with samples collected in March to May. HMO composition was similar to other previously reported cohorts. CONCLUSIONS: The HMO profile of Bangladeshi women is predominantly determined by secretor status. Context-specific HMO data may improve understanding of the effects of HMOs on the infant microbiome and health and guide the development of HMO-containing interventions

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

Background Infant cognitive development is influenced by maternal factors that range from obesity to early feeding and breast milk composition. Animal studies suggest a role for human milk oligosaccharide (HMO), 2&rsquo;-fucosyllactose (2&rsquo;FL), on learning and memory, yet no human studies have examined its impact on infant cognitive development relative to other HMOs and maternal factors. Objective To determine the impact of 2&rsquo;FL from breast milk feeding on infant cognitive development at 24 months of age relative to maternal obesity and breast milk feeding frequency. Methods and materials Hispanic mother-infant pairs (N = 50) were recruited across the spectrum of pre-pregnancy BMI. Breast milk was collected at 1 and 6 months, and feedings/day were reported. Nineteen HMOs were analyzed using high-performance liquid chromatography, with initial interest in 2&rsquo;FL. Infant cognitive development score was assessed with the Bayley-III Scale at 24 months. Linear regressions were used for prediction, and bootstrapping to determine mediation by 2&rsquo;FL. Results Maternal pre-pregnancy BMI was not related to feedings/day or HMOs, but predicted poorer infant cognitive development (&beta; = -0.31, P = 0.03). Feedings/day (&beta; = 0.34) and 2&rsquo;FL (&beta; = 0.59) at 1 month predicted better infant cognitive development (both P&le; 0.01). The association of feedings/day with infant cognitive development was no longer significant after further adjustment for 2&rsquo;FL (estimated mediation effect = 0.13, P = 0.04). There were no associations of feedings/day and 2&rsquo;FL at 6 months with infant cognitive development. Conclusions Our findings suggest that maternal factors influence infant cognitive development through multiple means. Though maternal obesity may be a separate negative influence, greater frequency of breast milk feeding at 1 month contributed to infant cognitive development through greater exposure to 2&rsquo;FL relative to other HMOs. The influence of 2&rsquo;FL was not significant at 6 months, indicating that early exposure to 2&rsquo;FL may be a critical temporal window for positively influencing infant cognitive development. </div