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

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

Nutrients ◽

10.3390/nu12061727 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1727

Author(s):

Carole Ayoub Moubareck ◽

Maryam Lootah ◽

Muna Tahlak ◽

Koen Venema

Keyword(s):

Breast Milk ◽

Human Milk ◽

Maternal Nutrition ◽

Geographic Location ◽

Rrna Gene ◽

Human Breast Milk ◽

Lactation Period ◽

Human Milk Oligosaccharides ◽

Microbial Composition ◽

Milk Oligosaccharides

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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Breast Milk Lipids and Fatty Acids in Regulating Neonatal Intestinal Development and Protecting against Intestinal Injury

Nutrients ◽

10.3390/nu12020534 ◽

2020 ◽

Vol 12 (2) ◽

pp. 534 ◽

Cited By ~ 4

Author(s):

David Ramiro-Cortijo ◽

Pratibha Singh ◽

Yan Liu ◽

Esli Medina-Morales ◽

William Yakah ◽

...

Keyword(s):

Fatty Acids ◽

Breast Milk ◽

Human Milk ◽

Preterm Infants ◽

Gastrointestinal Disease ◽

Essential Fatty Acids ◽

Intestinal Injury ◽

Human Breast Milk ◽

Intestinal Development ◽

Human Breast

Human breast milk is the optimal source of nutrition for infant growth and development. Breast milk fats and their downstream derivatives of fatty acids and fatty acid-derived terminal mediators not only provide an energy source but also are important regulators of development, immune function, and metabolism. The composition of the lipids and fatty acids determines the nutritional and physicochemical properties of human milk fat. Essential fatty acids, including long-chain polyunsaturated fatty acids (LCPUFAs) and specialized pro-resolving mediators, are critical for growth, organogenesis, and regulation of inflammation. Combined data including in vitro, in vivo, and human cohort studies support the beneficial effects of human breast milk in intestinal development and in reducing the risk of intestinal injury. Human milk has been shown to reduce the occurrence of necrotizing enterocolitis (NEC), a common gastrointestinal disease in preterm infants. Preterm infants fed human breast milk are less likely to develop NEC compared to preterm infants receiving infant formula. Intestinal development and its physiological functions are highly adaptive to changes in nutritional status influencing the susceptibility towards intestinal injury in response to pathological challenges. In this review, we focus on lipids and fatty acids present in breast milk and their impact on neonatal gut development and the risk of disease.

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An Insight into Probiotics Bio-Route: Translocation from the Mother’s Gut to the Mammary Gland

Applied Sciences ◽

10.3390/app11167247 ◽

2021 ◽

Vol 11 (16) ◽

pp. 7247

Author(s):

Shanmugaprakasham Selvamani ◽

Daniel Joe Dailin ◽

Vijai Kumar Gupta ◽

Mohd Wahid ◽

Ho Chin Keat ◽

...

Keyword(s):

Mammary Gland ◽

Human Milk ◽

Lymphatic Vessels ◽

Secretory Iga ◽

Intestinal Lumen ◽

Nutritional Requirement ◽

Human Breast Milk ◽

Microbial Composition ◽

Neonatal Immunity

Human breast milk (HBM) is unique in its composition as it is adapted to fulfil the newborns’ nutritional requirement and helps in improving the health of newborns. Besides various nutrients, the human milk also contains diverse group of microbiotas. The human milk microbiota has a remarkable impact on the growth and development of a newborn. Additionally, the human milk microbiota enhances the colonization of microbes in the gut of infants. Debates about the origin of HBM microbial flora remain premature and contradictory in some cases. Recent data suggest that the maternal gut microbiota has a major impact on microbial composition, areolar skin, and from the infant’s oral cavity. The current review investigates the possible route of microbial transfer from the maternal gut to mammary gland and suggests that it might occur through the entero-mammary pathway. It involves precise selection of probiotic microorganisms from the gut, as the human gut hosts trillions of microorganisms involved in gut homeostasis and other metabolic pathways. Gastrointestinal lymphatic vessels, macrophages, and dendritic cells are shown to play a significant role in the microbial transmission. Furthermore, the role of microbial factors in the development of neonatal immunity and translocation of secretory IgA (SIgA) cells from the intestinal lumen to GALT and finally to mammary glands via entero-mammary link are discussed.

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A Review of the Immunomodulating Components of Maternal Breast Milk and Protection Against Necrotizing Enterocolitis

Nutrients ◽

10.3390/nu12010014 ◽

2019 ◽

Vol 12 (1) ◽

pp. 14 ◽

Cited By ~ 14

Author(s):

Lila S. Nolan ◽

Olivia B. Parks ◽

Misty Good

Keyword(s):

Growth Factors ◽

Breast Milk ◽

Human Milk ◽

Necrotizing Enterocolitis ◽

Protective Factor ◽

Inflammatory Responses ◽

Newborn Infants ◽

Microbial Colonization ◽

Human Breast Milk ◽

Lactation Stage

Breast milk contains immunomodulating components that are beneficial to newborns during maturation of their immune system. Human breast milk composition is influenced by an infant’s gestational and chronological age, lactation stage, and the mother and infant’s health status. Major immunologic components in human milk, such as secretory immunoglobulin A (IgA) and growth factors, have a known role in regulating gut barrier integrity and microbial colonization, which therefore protect against the development of a life-threatening gastrointestinal illness affecting newborn infants called necrotizing enterocolitis (NEC). Breast milk is a known protective factor in the prevention of NEC when compared with feeding with commercial formula. Breast milk supplements infants with human milk oligosaccharides, leukocytes, cytokines, nitric oxide, and growth factors that attenuate inflammatory responses and provide immunological defenses to reduce the incidence of NEC. This article aims to review the variety of immunomodulating components in breast milk that protect the infant from the development of NEC.

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Human Breast Milk Contains Bovine lgG. Relationship to Infant Colic?

PEDIATRICS ◽

10.1542/peds.87.4.439 ◽

1991 ◽

Vol 87 (4) ◽

pp. 439-444

Author(s):

Patrick S. Clyne ◽

Anthony Kulczycki

Keyword(s):

Breast Milk ◽

Human Milk ◽

Milk Protein ◽

Cow’S Milk ◽

Human Breast Milk ◽

Human Breast ◽

Cow's Milk ◽

Milk Samples ◽

Infant Colic ◽

Β Lactoglobulin

Previous studies have suggested that an unidentified cow's milk protein, other than β-lactoglobulin and casein, might play a pathogenetic role in infant colic. Therefore, a radioimmunoassay was used to analyze human breast milk and infant formula samples for the presence of bovine IgG. Milk samples from 88 of the 97 mothers tested contained greater than 0.1 µg/mL of bovine IgG. In a study group of 59 mothers with infants in the colic-prone 2- to 17-week age group, the 29 mothers of colicky infants had higher levels of bovine IgG in their breast milk (median 0.42 µg/mL) than the 30 mothers of noncolicky infants (median 0.32 µg/mL) (P < .02). The highest concentrations of bovine IgG observed in human milk were 8.5 and 8.2 µg/mL. Most cow's milk-based infant formulas contained 0.6 to 6.4 µg/mL of bovine IgG, a concentration comparable with levels found in many human milk samples. The results suggest that appreciable quantities of bovine IgG are commonly present in human milk, that significantly higher levels are present in milk from mothers of colicky infants, and that bovine IgG may possibly be involved in the pathogenesis of infant colic.

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Riboflavin uptake transporter Slc52a2 (RFVT2) is upregulated in the mouse mammary gland during lactation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00507.2015 ◽

2016 ◽

Vol 310 (7) ◽

pp. R578-R585 ◽

Cited By ~ 8

Author(s):

Alex Man Lai Wu ◽

Liana Dedina ◽

Pooja Dalvi ◽

Mingdong Yang ◽

John Leon-Cheon ◽

...

Keyword(s):

Mammary Gland ◽

Breast Milk ◽

Milk Fat ◽

Fluorescent Protein ◽

Mammary Epithelial Cells ◽

Mdck Cells ◽

Basolateral Membrane ◽

Mouse Mammary Gland ◽

Transport Systems ◽

Human Breast Milk

While it is well recognized that riboflavin accumulates in breast milk as an essential vitamin for neonates, transport mechanisms for its milk excretion are not well characterized. The multidrug efflux transporter ABCG2 in the apical membrane of milk-producing mammary epithelial cells (MECs) is involved with riboflavin excretion. However, it is not clear whether MECs possess other riboflavin transport systems, which may facilitate its basolateral uptake into MECs. We report here that transcripts encoding the second ( SLC52A2) and third ( SLC52A3) member of the recently discovered family of SLC52A riboflavin uptake transporters are expressed in milk fat globules from human breast milk. Furthermore, Slc52a2 and Slc52a3 mRNA are upregulated in the mouse mammary gland during lactation. Importantly, the induction of Slc52a2, which was the major Slc52a riboflavin transporter in the lactating mammary gland, was also observed at the protein level. Subcellular localization studies showed that green fluorescent protein-tagged mouse SLC52A2 mainly localized to the cell membrane, with no preferential distribution to the apical or basolateral membrane in polarized kidney MDCK cells. These results strongly implicate a potential role for SLC52A2 in riboflavin uptake by milk-producing MECs, a critical step in the transfer of riboflavin into breast milk.

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Summary-The Early Feeds: Human Milk Versus Formula and Bovine Milk

PEDIATRICS ◽

10.1542/peds.75.1.157 ◽

1985 ◽

Vol 75 (1) ◽

pp. 157-159

Keyword(s):

Breast Milk ◽

Human Milk ◽

Whey Proteins ◽

Bovine Milk ◽

Milk Proteins ◽

Human Infant ◽

Postnatal Life ◽

Human Breast Milk ◽

Nonprotein Nitrogen ◽

Casein Protein

Adaptations of the gastrointestinal tract and the immune system that take place during the first year of postnatal life are of great importance, initially facilitating the transition between gestation and lactation, ultimately supporting independent postnatal life. When considering feeding options during the early periods, the roles of human milk, commercially prepared formula, and bovine milk must be evaluated in light of recent knowledge of these adaptations. Since infant feeding practices and the biologic capabilities of infants themselves vary significantly, the question arises as to what is "acceptable" v what is "optimal." NUTRITIONAL PROTEINS At present, evaluations of the amount of protein required for infant growth are based on clinical studies of largē populations and include a "margin of safety" to meet the needs of the individual infant. Based on the assumption that the milk of a given species is best adapted to the nutrient requirements of the young of that species, human infant protein requirements are determined by the protein contribution of human breast milk. Breast-milk proteins are defined broadly as either whey or casein protein with an approximate ratio of 70:30, respectively. The casein portion is divided into three subgroups: α,β and κ casein. Whey proteins are divided into six major subgroups: α-lactalbumin, β-lactoglobulin; lactoferrin; serum-albumin; lysozyme, and immunoglobulins A, G, and M. Numerous nonprotein nitrogen substances including taurine exist as well. Protein Availability Protein concentration of breast milk is approximately 1.2 g/dL when measured as total nitrogen. Nearly 25% of this is nonprotein nitrogen, much of which may not be used for nutritional purposes.

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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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Human Milk Oligosaccharide, Phospholipid, and Ganglioside Concentrations in Breast Milk from United Arab Emirates Mothers: Results from the MISC Cohort

Nutrients ◽

10.3390/nu11102400 ◽

2019 ◽

Vol 11 (10) ◽

pp. 2400 ◽

Cited By ~ 3

Author(s):

Paul McJarrow ◽

Hadia Radwan ◽

Lin Ma ◽

Alastair K.H. MacGibbon ◽

Mona Hashim ◽

...

Keyword(s):

Breast Milk ◽

Human Milk ◽

United Arab Emirates ◽

High Performance ◽

Post Partum ◽

Human Breast Milk ◽

Mature Milk ◽

Cross Sectional ◽

Significant Difference ◽

The Individual

Human milk oligosaccharides (HMOs), phospholipids (PLs), and gangliosides (GAs) are components of human breast milk that play important roles in the development of the rapidly growing infant. The differences in these components in human milk from the United Arab Emirates (UAE) were studied in a cross-sectional trial. High-performance liquid chromatography‒mass spectrometry was used to determine HMO, PL, and GA concentrations in transitional (5–15 days) and mature (at 6 months post-partum) breast milk of mothers of the United Arab Emirates (UAE). The results showed that the average HMO (12 species), PL (7 species), and GA (2 species) concentrations quantified in the UAE mothers’ transitional milk samples were (in mg/L) 8204 ± 2389, 269 ± 89, and 21.18 ± 11.46, respectively, while in mature milk, the respective concentrations were (in mg/L) 3905 ± 1466, 220 ± 85, and 20.18 ± 9.75. The individual HMO concentrations measured in this study were all significantly higher in transitional milk than in mature milk, except for 3 fucosyllactose, which was higher in mature milk. In this study, secretor and non-secretor phenotype mothers showed no significant difference in the total HMO concentration. For the PL and GA components, changes in the individual PL and GA species distribution was observed between transitional milk and mature milk. However, the changes were within the ranges found in human milk from other regions.

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Human Cytomegalovirus (HCMV) Reactivation in the Mammary Gland Induces a Proinflammatory Cytokine Shift in Breast Milk

Microorganisms ◽

10.3390/microorganisms8020289 ◽

2020 ◽

Vol 8 (2) ◽

pp. 289 ◽

Cited By ~ 2

Author(s):

Tabea Rabe ◽

Katrin Lazar ◽

Christoffer Cambronero ◽

Rangmar Goelz ◽

Klaus Hamprecht

Keyword(s):

Mammary Gland ◽

Breast Milk ◽

Human Cytomegalovirus ◽

Proinflammatory Cytokine ◽

Human Breast Milk ◽

Dna Dynamics ◽

Cytokine Network ◽

Milk Whey ◽

Mothers Of Preterm Infants ◽

The Impact

A locally restricted human cytomegalovirus (HCMV) reactivation in the mammary gland commonly occurs in nearly every IgG-seropositive breastfeeding mother. This unique phenomenon can therefore be used to study the reactivation process in an immunocompetent healthy host. Breast milk contains a variety of immunoactive compounds, including immune cells, antibodies, growth factors, and cytokines supporting the newborn’s immature immune system. To characterize the impact of HCMV reactivation on breast milk cytokines, we analyzed longitudinal breast milk samples of four IgG-seropositive and three IgG-seronegative mothers of preterm infants using Proximity Extension Assay (PEA) technology (Olink Proteomics, Uppsala, Sweden). Cytokine profiling revealed elevated cytokine levels in IgG-seropositive mothers’ milk whey. Reactivating mothers showed higher levels of CC-chemokines (MCP-2, CCL19, and CCL20) and CXC-chemokines (IL-8, CXCL9, CXCL10, and CXCL11), such as the proinflammatory cytokine IL-17C, glycoprotein CD5, and TNFSF14. HCMV reactivation seems to influence the cytokine profile in human breast milk. This work could open the door for further studies analyzing distinct relations of the cytokine network as well as phenotypical and functional T cell properties in background of HCMV DNA dynamics in early lactation.

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