Profiles of Human Milk Oligosaccharides and Their Relations to the Milk Microbiota of Breastfeeding Mothers in Dubai

The composition of human breast milk is affected by several factors, including genetics, geographic location and maternal nutrition. This study investigated the human milk oligosaccharides (HMOs) of breastfeeding mothers living in Dubai and their relations with the milk microbiota. A total of 30 breast milk samples were collected from healthy Emirati and UAE-expatriates at Latifa Hospital. HMO profiling was performed using UHPLC-MS. Microbiota profiles were determined by sequencing amplicons of the V3-V4 region of the 16S rRNA gene. HMO concentrations were significantly higher in Emirati, and dropped with the lactation period in both groups of mothers. The Le (a−b+)-secretor (Le+Se+) type was the most abundant in Dubai mothers (60%), followed by the Le(a−b−)-secretor (Le−Se+) type (23%). Bifidobacterium and Lactobacillus were considerably lower in Dubai-based mothers, while Pseudomonas and Delftia (Hydrogenophaga) were detected at a higher abundance compared to mothers from other countries. Atopobium was correlated with sialyl-lacto-N-tetraose c, Leptotrichia and Veillonella were correlated with 6’-sialyl-lactose, and Porphyromonas was correlated with lacto-N-hexaose. The study highlights the HMO profiles of breastfeeding mothers in Dubai and reveals few correlations with milk microbial composition. Targeted genomic analyses may help in determining whether these differences are due to genetic variations or to sociocultural and environmental factors.

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

Nutrients ◽

10.3390/nu12030826 ◽

2020 ◽

Vol 12 (3) ◽

pp. 826 ◽

Cited By ~ 1

Author(s):

Meichen Wang ◽

Zhenwen Zhao ◽

Ai Zhao ◽

Jian Zhang ◽

Wei Wu ◽

...

Keyword(s):

Breast Milk ◽

Human Milk ◽

Delivery Mode ◽

Human Breast Milk ◽

Lactation Period ◽

Human Milk Oligosaccharides ◽

Milk Oligosaccharides ◽

Term Infants ◽

Milk Samples ◽

Lactation Stage

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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New strategies for profiling and characterization of human milk oligosaccharides

Glycobiology ◽

10.1093/glycob/cwaa028 ◽

2020 ◽

Vol 30 (10) ◽

pp. 774-786 ◽

Cited By ~ 1

Author(s):

Sara Porfirio ◽

Stephanie Archer-Hartmann ◽

G Brett Moreau ◽

Girija Ramakrishnan ◽

Rashidul Haque ◽

...

Keyword(s):

Breast Milk ◽

Human Milk ◽

Milk Composition ◽

Human Breast Milk ◽

Human Milk Oligosaccharides ◽

Bacterial Strains ◽

Milk Oligosaccharides ◽

Vast Number ◽

The Impact

Abstract Human breast milk is an incredibly rich and complex biofluid composed of proteins, lipids and complex carbohydrates, including a diverse repertoire of free human milk oligosaccharides (HMOs). Strikingly, HMOs are not digested by the infant but function as prebiotics for bacterial strains associated with numerous benefits. Considering the broad variety of beneficial effects of HMOs, and the vast number of factors that affect breast milk composition, the analysis of HMO diversity and complexity is of utmost relevance. Using human milk samples from a cohort of Bangladeshi mothers participating in a study on malnutrition and stunting in children, we have characterized breast milk oligosaccharide composition by means of permethylation followed by liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-MS/MS) analysis. This approach identified over 100 different glycoforms and showed a wide diversity of milk composition, with a predominance of fucosylated and sialylated HMOs over nonmodified HMOs. We observed that these samples contain on average 80 HMOs, with the highest permethylated masses detected being >5000 mass units. Here we report an easily implemented method developed for the separation, characterization and relative quantitation of large arrays of HMOs, including higher molecular weight sialylated HMOs. Our ultimate goal is to create a simple, high-throughput method, which can be used for full characterization of sialylated and/or fucosylated HMOs. These results demonstrate how current analytical techniques can be applied to characterize human milk composition, providing new tools to help the scientific community shed new light on the impact of HMOs during infant development.

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In Love with Shaping You—Influential Factors on the Breast Milk Content of Human Milk Oligosaccharides and Their Decisive Roles for Neonatal Development

Nutrients ◽

10.3390/nu12113568 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3568

Author(s):

Christian Hundshammer ◽

Oliver Minge

Keyword(s):

Breast Milk ◽

Human Milk ◽

Influential Factors ◽

Human Breast Milk ◽

Human Milk Oligosaccharides ◽

Milk Oligosaccharides ◽

Neonatal Development ◽

Potential Health ◽

Depth Analysis

Human milk oligosaccharides (HMOs) are structurally versatile sugar molecules constituting the third major group of soluble components in human breast milk. Based on the disaccharide lactose, the mammary glands of future and lactating mothers produce a few hundreds of different HMOs implicating that their overall anabolism utilizes rather high amounts of energy. At first sight, it therefore seems contradictory that these sugars are indigestible for infants raising the question of why such an energy-intensive molecular class evolved. However, in-depth analysis of their molecular modes of action reveals that Mother Nature created HMOs for neonatal development, protection and promotion of health. This is not solely facilitated by HMOs in their indigestible form but also by catabolites that are generated by microbial metabolism in the neonatal gut additionally qualifying HMOs as natural prebiotics. This narrative review elucidates factors influencing the HMO composition as well as physiological roles of HMOs on their way through the infant body and within the gut, where a major portion of HMOs faces microbial catabolism. Concurrently, this work summarizes in vitro, preclinical and observational as well as interventional clinical studies that analyzed potential health effects that have been demonstrated by or were related to either human milk-derived or synthetic HMOs or HMO fractions.

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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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Bovine Milk Oligosaccharides and Human Milk Oligosaccharides Modulate the Gut Microbiota Composition and Volatile Fatty Acid Concentrations in a Preclinical Neonatal Model

Microorganisms ◽

10.3390/microorganisms9050884 ◽

2021 ◽

Vol 9 (5) ◽

pp. 884

Author(s):

Mei Wang ◽

Marcia H. Monaco ◽

Jonas Hauser ◽

Jian Yan ◽

Ryan N. Dilger ◽

...

Keyword(s):

Fatty Acid ◽

Human Milk ◽

Volatile Fatty Acid ◽

Bovine Milk ◽

Rrna Gene ◽

Microbiota Composition ◽

Human Milk Oligosaccharides ◽

Microbial Composition ◽

Milk Oligosaccharides ◽

The Impact

Milk oligosaccharides (OS) shape microbiome structure and function, but their relative abundances differ between species. Herein, the impact of the human milk oligosaccharides (HMO) (2′-fucosyllactose [2′FL] and lacto-N-neotetraose [LNnT]) and OS isolated from bovine milk (BMOS) on microbiota composition and volatile fatty acid (VFA) concentrations in ascending colon (AC) contents and feces was assessed. Intact male piglets received diets either containing 6.5 g/L BMOS (n = 12), 1.0 g/L 2′FL + 0.5 g/L LNnT (HMO; n = 12), both (HMO + BMOS; n = 10), or neither (CON; n = 10) from postnatal day (PND) 2 to 34. Microbiota were assessed by 16S rRNA gene sequencing and real-time PCR, and VFA were measured by gas chromatography. The microbiota was affected by OS in an intestine region-specific manner. BMOS reduced (p < 0.05) microbial richness in the AC, microbiota composition in the AC and feces, and acetate concentrations in AC, regardless of HMO presence. HMO alone did not affect overall microbial composition, but increased (p < 0.05) the relative proportion of specific taxa, including Blautia, compared to other groups. Bacteroides abundance was increased (p < 0.05) in the AC by BMOS and synergistically by BMOS + HMO in the feces. Distinct effects of HMO and BMOS suggest complementary and sometimes synergistic benefits of supplementing a complex mixture of OS to formula.

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Does the contribution of human milk oligosaccharides to the beneficial effects of breast milk allow us to hope for an improvement in infant formulas?

Critical Reviews in Food Science and Nutrition ◽

10.1080/10408398.2020.1761772 ◽

2020 ◽

pp. 1-12

Author(s):

Jean-Pierre Chouraqui

Keyword(s):

Breast Milk ◽

Human Milk ◽

Infant Formulas ◽

Human Milk Oligosaccharides ◽

Milk Oligosaccharides ◽

Beneficial Effects

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Low Diversity of Human Milk Oligosaccharides is Associated with Necrotising Enterocolitis in Extremely Low Birth Weight Infants

Nutrients ◽

10.3390/nu10101556 ◽

2018 ◽

Vol 10 (10) ◽

pp. 1556 ◽

Cited By ~ 10

Author(s):

Erik Wejryd ◽

Magalí Martí ◽

Giovanna Marchini ◽

Anna Werme ◽

Baldvin Jonsson ◽

...

Keyword(s):

Birth Weight ◽

Breast Milk ◽

Low Birth Weight ◽

Human Milk ◽

Amperometric Detection ◽

Exchange Chromatography ◽

Extremely Low Birth Weight ◽

Human Milk Oligosaccharides ◽

Low Birth Weight Infants ◽

Milk Oligosaccharides

Difference in human milk oligosaccharides (HMO) composition in breast milk may be one explanation why some preterm infants develop necrotizing enterocolitis (NEC) despite being fed exclusively with breast milk. The aim of this study was to measure the concentration of 15 dominant HMOs in breast milk during the neonatal period and investigate how their levels correlated to NEC, sepsis, and growth in extremely low birth weight (ELBW; <1000 g) infants who were exclusively fed with breast milk. Milk was collected from 91 mothers to 106 infants at 14 and 28 days and at postmenstrual week 36. The HMOs were analysed with high-performance anion-exchange chromatography with pulsed amperometric detection. The HMOs diversity and the levels of Lacto-N-difucohexaose I were lower in samples from mothers to NEC cases, as compared to non-NEC cases at all sampling time points. Lacto-N-difucohexaose I is only produced by secretor and Lewis positive mothers. There were also significant but inconsistent associations between 3′-sialyllactose and 6′-sialyllactose and culture-proven sepsis and significant, but weak correlations between several HMOs and growth rate. Our results suggest that the variation in HMO composition in breast milk may be an important factor explaining why exclusively breast milk fed ELBW infants develop NEC.

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Efforts to emulate human milk oligosaccharides

British Journal Of Nutrition ◽

10.1017/s0007114507838062 ◽

2007 ◽

Vol 98 (S1) ◽

pp. S74-S79 ◽

Cited By ~ 21

Author(s):

Rosa María Espinosa ◽

Martha Taméz ◽

Pedro Prieto

Keyword(s):

Breast Milk ◽

Human Milk ◽

Current Knowledge ◽

Biological Effects ◽

Historical Context ◽

Published Data ◽

Human Milk Oligosaccharides ◽

Milk Oligosaccharides ◽

Fast Analysis ◽

Chemical Structures

Research on human milk oligosaccharides (HMO) began with the characterisation of their chemical structures and is now focused on the elucidation of their biological roles. Previously, biological effects could only be investigated with fractions or structures isolated from breast milk; consequently, clinical observations were limited to comparisons between outcomes from breast-fed infants and their formula-fed counterparts. In some cases, it was inferred that the observed differences were caused by the presence of HMO in breast milk. Presently, analytical techniques allow for the fast analysis of milk samples, thus providing insights on the inherent variability of specimens. In addition, methods for the synthesis of HMO have provided single structures in sufficient quantities to perform clinical studies with oligosaccharide-supplemented formulae. Furthermore, studies have been conducted with non-mammalian oligosaccharides with the purpose of assessing the suitability of these structures to functionally emulate HMO. Taken together, these developments justify summarising current knowledge on HMO to further discussions on efforts to emulate human milk in regard to its oligosaccharide content. The present account summarises published data and intends to provide an historical context and to illustrate the state of the field.

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Breast Milk, a Source of Beneficial Microbes and Associated Benefits for Infant Health

Nutrients ◽

10.3390/nu12041039 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1039 ◽

Cited By ~ 11

Author(s):

Katríona E. Lyons ◽

C. Anthony Ryan ◽

Eugene M. Dempsey ◽

R. Paul Ross ◽

Catherine Stanton

Keyword(s):

Mammary Gland ◽

Breast Milk ◽

Human Milk ◽

Infant Health ◽

Gastrointestinal Disease ◽

Newborn Infants ◽

Human Breast Milk ◽

Microbial Composition ◽

Beneficial Microbes ◽

Health And Nutrition

Human breast milk is considered the optimum feeding regime for newborn infants due to its ability to provide complete nutrition and many bioactive health factors. Breast feeding is associated with improved infant health and immune development, less incidences of gastrointestinal disease and lower mortality rates than formula fed infants. As well as providing fundamental nutrients to the growing infant, breast milk is a source of commensal bacteria which further enhance infant health by preventing pathogen adhesion and promoting gut colonisation of beneficial microbes. While breast milk was initially considered a sterile fluid and microbes isolated were considered contaminants, it is now widely accepted that breast milk is home to its own unique microbiome. The origins of bacteria in breast milk have been subject to much debate, however, the possibility of an entero-mammary pathway allowing for transfer of microbes from maternal gut to the mammary gland is one potential pathway. Human milk derived strains can be regarded as potential probiotics; therefore, many studies have focused on isolating strains from milk for subsequent use in infant health and nutrition markets. This review aims to discuss mammary gland development in preparation for lactation as well as explore the microbial composition and origins of the human milk microbiota with a focus on probiotic development.

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Influence of sulfonated and diet-derived human milk oligosaccharides on the infant microbiome and immune markers

Journal of Biological Chemistry ◽

10.1074/jbc.ra119.011351 ◽

2020 ◽

Vol 295 (12) ◽

pp. 4035-4048 ◽

Cited By ~ 4

Author(s):

Candice Quin ◽

Sara D. Vicaretti ◽

Nina A Mohtarudin ◽

Alexander M. Garner ◽

Deanna M. Vollman ◽

...

Keyword(s):

Fatty Acids ◽

Breast Milk ◽

Human Milk ◽

Unsaturated Fatty Acids ◽

Maternal Diet ◽

Intestinal Microbiome ◽

Human Milk Oligosaccharides ◽

Immune Markers ◽

Milk Oligosaccharides ◽

Milk Fatty Acids

Human milk oligosaccharides (HMOs) promote the development of the neonatal intestinal, immune, and nervous systems and has recently received considerable attention. Here we investigated how the maternal diet affects HMO biosynthesis and how any diet-induced HMO alterations influence the infant gut microbiome and immunity. Using capillary electrophoresis and MS-based analyses, we extracted and measured HMOs from breast milk samples and then correlated their levels with results from validated 24-h diet recall surveys and breast milk fatty acids. We found that fruit intake and unsaturated fatty acids in breast milk were positively correlated with an increased absolute abundance of numerous HMOs, including 16 sulfonated HMOs we identified here in humans for the first time. The diet-derived monosaccharide 5-N-glycolyl-neuraminic acid (Neu5Gc) was unambiguously detected in all samples. To gain insights into the potential impact of Neu5Gc on the infant microbiome, we used a constrained ordination approach and identified correlations between Neu5Gc levels and Bacteroides spp. in infant stool. However, Neu5Gc was not associated with marked changes in infant immune markers, in contrast with sulfonated HMOs, whose expression correlated with suppression of two major Th2 cytokines, IL-10 and IL-13. The findings of our work highlight the importance of maternal diet for HMO biosynthesis and provide as yet unexplored targets for future studies investigating interactions between HMOs and the intestinal microbiome and immunity in infants.

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