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

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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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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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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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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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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Detectable Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Human Breast Milk of a Mildly Symptomatic Patient With Coronavirus Disease 2019 (COVID-19)

Clinical Infectious Diseases ◽

10.1093/cid/ciaa673 ◽

2020 ◽

Cited By ~ 18

Author(s):

Patrick C K Tam ◽

Kathleen M Ly ◽

Max L Kernich ◽

Nicola Spurrier ◽

Diana Lawrence ◽

...

Keyword(s):

Case Report ◽

Breast Milk ◽

Severe Acute Respiratory Syndrome ◽

Human Milk ◽

Symptomatic Patient ◽

Clinical Samples ◽

Human Breast Milk ◽

Causative Pathogen ◽

Human Breast ◽

Novel Coronavirus

Abstract SARS-CoV-2 is a novel coronavirus and causative pathogen to the pandemic illness COVID-19. Although RNA has been detected in various clinical samples, no reports to date have documented SARS-CoV-2 in human milk. This case report describes an actively breastfeeding patient with COVID-19 infection with detectable viral RNA in human milk.

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Necrotizing Enterocolitis: Protective Factor in Breast Milk

New England Journal of Medicine ◽

10.1056/nejm197604082941518 ◽

1976 ◽

Vol 294 (15) ◽

pp. 844-845 ◽

Cited By ~ 2

Keyword(s):

Breast Milk ◽

Necrotizing Enterocolitis ◽

Protective Factor

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Inhibitors of Complement Activity in Human Breast-Milk: A Proposed Hypothesis of Their Physiological Significance

Mediators of Inflammation ◽

10.1080/09629359990559 ◽

1999 ◽

Vol 8 (2) ◽

pp. 69-75 ◽

Cited By ~ 14

Author(s):

Michael Oladipo Ogundele

Keyword(s):

Breast Milk ◽

Human Milk ◽

Complement Activation ◽

Milk Fat ◽

Physiological Significance ◽

Human Breast Milk ◽

Human Breast ◽

Complement Activity ◽

Milk Fat Globule ◽

Fat Globule

Several natural components abundant in the fluid phase of human breast-milk have been shown to be inhibitors of complement activationin vitro, particularly the classical pathway. These include lysozyme, lactoferrin, lactalbumin alpha and other ligand chelators, complement regulator proteins and other specific soluble inhibitors of complement activation. Their physiological significance probably resides in their ability to restrictin vivocomplement activation to specialized (compartmentalized) sites on the cellular membrane structures in human milk, represented by the abundant surface area of the milk fat globule membranes. This would serve to prevent inflammatory-induced tissue damage of the delicate immature gastrointestinal tract of the newborn as well as the mammary gland itself. A number of recognized and potential inhibitors of complement activity in human milk and other biological fluids are hereby reviewed, with a proposal of their physiological significance.Abbreviations: HBM, human breast-milk; APC, alternative complement activation pathway; MAC, membrane attack complex (C5b-9); MFGM, milk fat globule membrane

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COVID-19 mRNA vaccine is not detected in human milk

10.1101/2021.03.05.21252998 ◽

2021 ◽

Cited By ~ 1

Author(s):

Yarden Golan ◽

Mary Prahl ◽

Arianna Cassidy ◽

Christine Y. Lin ◽

Nadav Ahituv ◽

...

Keyword(s):

Clinical Trials ◽

High Risk ◽

Breast Milk ◽

Human Milk ◽

Human Breast Milk ◽

Human Breast ◽

Phase 3 ◽

Milk Samples

AbstractSeveral countries have recently approved the use of mRNA vaccines against COVID-19 under an emergency use authorization. However, no pregnant or lactating individuals were included in the Phase 3 clinical trials of these vaccines despite belonging to a group at high risk for severe complications of COVID-19 infection. We show here that the mRNA from anti-COVID BNT162b2 (Pfizer) and mRNA-1273 (Moderna) vaccines is not detected in human breast milk samples collected 4-48 hours post-vaccine. These results strengthen the recommendation of ABM and WHO that lactating individuals who receive the anti-COVID-19 mRNA-based vaccine should continue to breastfeed their infants uninterrupted.

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