Maternal and Infant Factors Associated with Human Milk Oligosaccharides Concentrations According to Secretor and Lewis Phenotypes

Human milk oligosaccharides (HMOs) are multifunctional carbohydrates naturally present in human milk that act as prebiotics, prevent pathogen binding and infections, modulate the immune system and may support brain development in infants. HMOs composition is very individualized and differences in HMOs concentrations may affect the infant’s health. HMOs variability can be partially explained by the activity of Secretor (Se) and Lewis (Le) genes in the mother, but non-genetic maternal factors may also be involved. In this cross-sectional, observational study, 78 single human milk samples ranging from 17 to 76 days postpartum (median: 32 days, IQR: 25–46 days) were collected from breastfeeding Brazilian women, analyzed for 16 representative HMOs by liquid chromatography coupled to mass spectrometry and associations between maternal and infant factors with HMOs concentrations were investigated. HMOs concentrations presented a high variability even in women with the same SeLe phenotype and associations with maternal allergic disease, time postpartum and with infant’s weight, weight gain and sex. Overall, we present unprecedented data on HMOs concentrations from breastfeeding Brazilian women and novel associations of maternal allergic disease and infant’s sex with HMOs concentrations. Differences in HMOs composition attributed to maternal SeLe phenotype do not impact infant growth, but higher concentrations of specific HMOs may protect against excessive weight gain.

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What Are the Maternal Factors That Potentially Intervenes in the Nutritional Composition of Human Milk?

Nutrients ◽

10.3390/nu13051587 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1587

Author(s):

Yasmin Amaral ◽

Leila Silva ◽

Fernanda Soares ◽

Daniele Marano ◽

Sylvia Nehab ◽

...

Keyword(s):

Weight Gain ◽

Nutritional Status ◽

Human Milk ◽

Gestational Weight Gain ◽

Post Partum ◽

Cross Sectional Study ◽

Nutritional Composition ◽

Cross Sectional ◽

Factors Associated ◽

Gestational Weight

Background: To evaluate the potential factors associated with the nutritional composition of human milk of puerperal women. Methods: cross-sectional study, conducted between March 2016 and August 2017, with 107 women, selected in a Tertiary Health Care Tertiary Health Facility of the Unified Health System (SUS) in the Municipality of Rio de Janeiro. Data were collected two months after delivery. The dependent variable of the study was the nutritional composition of human milk. We divided the independent variables into hierarchical levels: distal (age, schooling, parity and pregestational nutritional status), intermediate (number of prenatal visits and gestational weight gain) and proximal (alcohol consumption, smoking, diabetes mellitus and hypertension). For data analysis, we applied the multiple linear regression, centered on the hierarchical model. Only the variables associated with the nutritional composition of breast milk remained in the final model at a 5% level of significance. Results: The nutritional composition of human milk yielded by women with pregestational overweight, smokers and hypertensive had higher amounts of lipids and energy. Conversely, women with gestational weight gain below the recommended had lower amounts of these components. Conclusion: The evaluation of factors associated with the nutritional composition of human milk is extremely important to assist post-partum care practices. In this study, we observed that lipid and energy contents were associated to pregestational nutritional status, gestational weight gain, smoking and hypertension.

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Human Milk Oligosaccharides and Infant Weight in the First 6 Months of Life (P11-053-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz048.p11-053-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Cited By ~ 2

Author(s):

Paige Berger ◽

Jasmine Plows ◽

Roshonda Jones ◽

Tanya Alderete ◽

Chloe Yonemitsu ◽

...

Keyword(s):

Weight Gain ◽

Human Milk ◽

Kidney Diseases ◽

Total Sample ◽

Human Milk Oligosaccharides ◽

Milk Oligosaccharides ◽

Secretor Status ◽

Funding Sources ◽

Milk Components ◽

Infant Weight Gain

Abstract Objectives The effects of breastfeeding on reduced risk of obesity are inconclusive, although smaller studies suggest that specific human milk components may be relevant to infant weight gain. The primary aim of this study was to determine whether individual human milk oligosaccharides (HMOs) in the first month of life are associated with infant weight in the first 6 months of life. A secondary aim was to assess associations separately by HMO secretor status. Methods Participants were 156 Hispanic mother-infant pairs. Breast milk was collected at 1 month. HMO composition was analyzed using high-pressure liquid chromatography, and HMO secretor status was determined by the presence or near absence of 2’-fucosyllactose or lacto-N-fucopentaose (LNFP) I. Infant weight was measured at 1 and 6 months, and infant weight-for-age z scores (WAZ) and WAZ changes were calculated. Multiple linear regressions were used to examine the effect of HMO composition on WAZ, adjusting for maternal age, pre-pregnancy BMI, infant age, sex, and birth weight. Results In the total sample, HMO composition at 1 month was not significantly associated with WAZ at 1 month. In the total sample, higher LNFPII at 1 month predicted lower WAZ gain (β = –0.27, P = 0.01) and lower WAZ status (β = –0.26, P = 0.01) at 6 months. In infants of secretor mothers, higher LNFPII at 1 month predicted lower WAZ gain at 6 months (β = –0.23, P = 0.02); in infants of non-secretor mothers, LNFPII at 1 month predicted lower WAZ status at 6 months (β = –0.40, P = 0.03). Similar significant associations were observed when infant weight replaced WAZ in the models. No other HMOs were significantly related to infant WAZ or weight. Conclusions Our data suggest that greater exposure to LNFPII in the first month of life may be protective against rapid infant weight gain in the first 6 months, regardless of HMO secretor status. These findings provide additional evidence that specific human milk components may diminish infant obesity risk. Funding Sources Supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIH R01 DK110793) and the Gerber Foundation.

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Human Milk Oligosaccharides modulate the risk for preterm birth in a microbiome dependent and independent manner

10.1101/683714 ◽

2019 ◽

Cited By ~ 3

Author(s):

Manuela-Raluca Pausan ◽

Vassiliki Kolovetsiou-Kreiner ◽

Gesa Lucia Richter ◽

Tobias Madl ◽

Elisabeth Giselbrecht ◽

...

Keyword(s):

Preterm Birth ◽

Human Milk ◽

Sterile Inflammation ◽

Human Milk Oligosaccharides ◽

Spontaneous Preterm Birth ◽

Milk Oligosaccharides ◽

Short Cervix ◽

Independent Manner ◽

Cross Sectional ◽

Urinary Microbiome

AbstractBackgroundPreterm birth is one of the leading causes of neonatal mortality. The causes for spontaneous preterm birth (PTB) are multifactorial and remain often unknown. In this study, we tested the hypothesis that human milk oligosaccharides (HMOs) in blood and urine modulate the maternal urinary and vaginal microbiome and influence the risk for PTB. We analyzed the vaginal and urinary microbiome of a cross-sectional cohort of women with and without preterm labor and correlated our findings with measurements of metabolites and HMOs in urine and blood.ResultsWe identified several microbial signatures associated with short cervix, PTB and/or preterm contractions such asLactobacillus jensenii,L. gasseri,Ureaplasma sp. andGardnerella sp..Additionally, we observed associations between sialylated HMOs, in particular 3’-sialyllactose, with PTB, short cervix and increased inflammation and confirmed an influence of HMOs on the microbiome profile.ConclusionsIdentifying serum and urinary HMOs and several key microorganisms associated with PTB, our findings point at two distinct processes modulating the risk for PTB. One process seems to be driven by sterile inflammation, characterized by increased concentrations of sialylated HMOs in serum. Another process might be microbiome-mediated, potentially driven by secretor-active HMOs in urine. Our results support current efforts to improve diagnostics and therapeutic strategies.

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Human Milk Oligosaccharides and Hispanic Infant Weight Gain in the First 6 Months

Obesity ◽

10.1002/oby.22884 ◽

2020 ◽

Vol 28 (8) ◽

pp. 1519-1525

Author(s):

Paige K. Berger ◽

Jasmine F. Plows ◽

Roshonda B. Jones ◽

Tanya L. Alderete ◽

Chloe Yonemitsu ◽

...

Keyword(s):

Weight Gain ◽

Human Milk ◽

Human Milk Oligosaccharides ◽

Milk Oligosaccharides ◽

Infant Weight Gain

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Human Milk Oligosaccharides (HMOs) and Infant Microbiota: A Scoping Review

Foods ◽

10.3390/foods10061429 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1429

Author(s):

Cristina Sánchez ◽

Cristina Fente ◽

Patricia Regal ◽

Alexandre Lamas ◽

María Paz Lorenzo

Keyword(s):

Breast Milk ◽

Human Milk ◽

Mode Of Delivery ◽

Geographic Location ◽

Microbial Colonization ◽

Human Milk Oligosaccharides ◽

Maternal Factors ◽

Milk Oligosaccharides ◽

Breastfed Infants ◽

The Impact

Human milk oligosaccharides (HMOs) are the third most abundant solid component of breast milk. However, the newborn cannot assimilate them as nutrients. They are recognized prebiotic agents (the first in the newborn diet) that stimulate the growth of beneficial microorganisms, mainly the genus Bifidobacterium, dominant in the gut of breastfed infants. The structures of the oligosaccharides vary mainly according to maternal genetics, but also other maternal factors such as parity and mode of delivery, age, diet, and nutritional status or even geographic location and seasonality cause different breast milk oligosaccharides profiles. Differences in the profiles of HMO have been linked to breast milk microbiota and gut microbial colonization of babies. Here, we provide a review of the scope of reports on associations between HMOs and the infant gut microbiota to assess the impact of HMO composition.

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Human Milk Oligosaccharides Modulate the Risk for Preterm Birth in a Microbiome-Dependent and -Independent Manner

mSystems ◽

10.1128/msystems.00334-20 ◽

2020 ◽

Vol 5 (3) ◽

Author(s):

Manuela-Raluca Pausan ◽

Vassiliki Kolovetsiou-Kreiner ◽

Gesa Lucia Richter ◽

Tobias Madl ◽

Elisabeth Giselbrecht ◽

...

Keyword(s):

Preterm Birth ◽

Human Milk ◽

Sterile Inflammation ◽

Vaginal Microbiome ◽

Human Milk Oligosaccharides ◽

Milk Oligosaccharides ◽

Short Cervix ◽

Independent Manner ◽

Cross Sectional ◽

Content Type

ABSTRACT Preterm birth (PTB) is one of the leading causes of neonatal mortality. The causes for spontaneous PTB are multifactorial and often remain unknown. In this study, we tested the hypothesis that human milk oligosaccharides (HMOs) in blood and urine modulate the maternal urinary and vaginal microbiome and influence the risk for PTB. We analyzed the vaginal and urinary microbiome of a cross-sectional cohort of women with or without preterm labor and correlated our findings with measurements of metabolites and HMOs in urine and blood. We identified several microbial signatures, such as Lactobacillus jensenii, L. gasseri, Ureaplasma sp., and Gardnerella sp., associated with a short cervix, PTB, and/or preterm contractions. In addition, we observed associations between sialylated HMOs, in particular 3′-sialyllactose, with PTB, short cervix, and increased inflammation and confirmed an influence of HMOs on the microbiome profile. Since they identify serum and urinary HMOs and several key microorganisms associated with PTB, our findings point at two distinct processes modulating the risk for PTB. One process seems to be driven by sterile inflammation, characterized by increased concentrations of sialylated HMOs in serum. Another process might be microbiome mediated and potentially associated with specific HMO signatures in urine. Our results support current efforts to improve diagnostics and therapeutic strategies in PTB. IMPORTANCE The causes for preterm birth (PTB) often remain elusive. We investigated whether circulating human milk oligosaccharides (HMOs) might be involved in modulating urinary and vaginal microbiome promoting or preventing PTB. We identified here HMOs and key microbial taxa associated with indicators of PTB. Based on our results, we propose two models for how HMOs might modulate risk for PTB: (i) by changes in HMOs associated with sterile inflammation (microbiome-independent) and (ii) by HMO-driven shifts in microbiome (microbiome-dependent). Our findings will guide current efforts to better predict the risk for PTB in seemingly healthy pregnant women and also provide appropriate preventive strategies.

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