Human Milk, More Than Simple Nourishment

Human breast milk not only has nutritional properties but also holds a functional role. It contains various bioactive factors (lactoferrin, lysozyme, leukocytes, immunoglobulins, cytokines, hormones, human milk oligosaccharides, microbiome, microRNAs and stem cells) shown to contribute to several short- and long-term health outcomes. Some of these factors appear to be involved in the infant’s neuro-cognitive development, anti-oncogenic processes, cellular communication and differentiation. Furthermore, breast milk is increasingly recognized to have dynamic characteristics and to play a fundamental role in the cross-talking mother-neonate. This narrative review aims to provide a summary and an update on these bioactive substances, exploring their functions mainly on immunomodulation, microbiome and virome development. Although the knowledge about breast milk potentiality has significantly improved, leading to discovering unexpected functions, the exact mechanisms with which breast milk exercises its bioactivity have not been completely clarified. This can represent a fertile ground for exploring and understanding the complexity behind these functional elements to develop new therapeutic strategies.

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Short- and Long-Term Implications of Human Milk Microbiota on Maternal and Child Health

International Journal of Molecular Sciences ◽

10.3390/ijms222111866 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11866

Author(s):

María García-Ricobaraza ◽

José Antonio García-Santos ◽

Mireia Escudero-Marín ◽

Estefanía Diéguez ◽

Tomás Cerdó ◽

...

Keyword(s):

Breast Milk ◽

Human Milk ◽

Milk Fat ◽

Current Knowledge ◽

Nutritional Composition ◽

Biologically Active ◽

Human Breast Milk ◽

Gut Colonization ◽

Short And Long Term

Human milk (HM) is considered the most complete food for infants as its nutritional composition is specifically designed to meet infant nutritional requirements during early life. HM also provides numerous biologically active components, such as polyunsaturated fatty acids, milk fat globules, IgA, gangliosides or polyamines, among others; in addition, HM has a “bifidogenic effect”, a prebiotic effect, as a result of the low concentration of proteins and phosphates, as well as the presence of lactoferrin, lactose, nucleotides and oligosaccharides. Recently, has been a growing interest in HM as a potential source of probiotics and commensal bacteria to the infant gut, which might, in turn, influence both the gut colonization and maturation of infant immune system. Our review aims to address practical approaches to the detection of microbial communities in human breast milk samples, delving into their origin, composition and functions. Furthermore, we will summarize the current knowledge of how HM microbiota dysbiosis acts as a short- and long-term predictor of maternal and infant health. Finally, we also provide a critical view of the role of breast milk-related bacteria as a novel probiotic strategy in the prevention and treatment of maternal and offspring diseases.

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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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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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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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Dietary Habits and Relationship with the Presence of Main and Trace Elements, Bisphenol A, Tetrabromobisphenol A, and the Lipid, Microbiological and Immunological Profiles of Breast Milk

Nutrients ◽

10.3390/nu13124346 ◽

2021 ◽

Vol 13 (12) ◽

pp. 4346

Author(s):

Irma Castro ◽

Rebeca Arroyo ◽

Marina Aparicio ◽

María Ángeles Martínez ◽

Joaquim Rovira ◽

...

Keyword(s):

Trace Elements ◽

Breast Milk ◽

Bisphenol A ◽

Human Milk ◽

Dietary Habits ◽

Immunological Profile ◽

Early Life Exposure ◽

Study Support ◽

Short And Long Term

Breastfeeding is the best way to feed an infant, although it can also be a source of abiotic contaminants such as heavy metals or bisphenol A (BPA). The early life exposure to these compounds can lead to serious toxic effects in both the short and long-term. These substances can reach breast milk through the mother’s habits, diet being one of the main routes of exposure. The aim of the present work was to analyse possible associations between the dietary habits of women and the content of major trace elements, BPA, fatty acids and lipids, and the microbiological and immunological profiles of human milk. Possible associations between major trace elements and BPA and the lipid, microbiological and immunological profiles were also analysed. The results of this study support that the microbiological composition of human milk is associated with the dietary habits of the women, and that the consumption of canned drinks is related to the presence of BPA in human milk. Furthermore, some relationships were found between the amount of major trace elements and the microbiological and immunological profile of the milk samples. Finally, the presence of BPA was associated with changes in the immunological profile of human milk.

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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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Nordic study on human milk fortification in extremely preterm infants: a randomised controlled trial—the N-forte trial

BMJ Open ◽

10.1136/bmjopen-2021-053400 ◽

2021 ◽

Vol 11 (11) ◽

pp. e053400

Author(s):

Georg Bach Jensen ◽

Fredrik Ahlsson ◽

Magnus Domellöf ◽

Anders Elfvin ◽

Lars Naver ◽

...

Keyword(s):

Breast Milk ◽

Human Milk ◽

Preterm Infants ◽

Ethical Review ◽

Human Breast Milk ◽

Human Breast ◽

Preterm Formula ◽

Extremely Preterm ◽

Extremely Preterm Infants ◽

Randomised Controlled

IntroductionThe mortality rate of extremely low gestational age (ELGA) (born <gestational week 28+0) infants remains high, and severe infections and necrotising enterocolitis (NEC) are common causes of death. Preterm infants receiving human milk have lower incidence of sepsis and NEC than those fed a bovine milk-based preterm formula. Despite this, fully human milk fed ELGA infants most often have a significant intake of cow’s milk protein from bovine-based protein fortifier. The aim of this study is to evaluate whether the supplementation of human milk-based, as compared with bovine-based, nutrient fortifier reduces the prevalence of NEC, sepsis and mortality in ELGA infants exclusively fed with human milk.Methods and analysisA randomised-controlled multicentre trial comparing the effect of a human breast milk-based fortifier with a standard bovine protein-based fortifier in 222–322 ELGA infants fed human breast milk (mother’s own milk and/or donor milk). The infants will be randomised to either fortifier before reaching 100 mL/kg/day in oral feeds. The intervention, stratified by centre, will continue until the target postmenstrual week 34+0. The primary outcome is a composite of NEC, sepsis or death. Infants are characterised with comprehensive clinical and nutritional data collected prospectively from birth until hospital discharge. Stool, urine, blood and breast milk samples are collected for analyses in order to study underlying mechanisms. A follow-up focusing on neurological development and growth will be performed at 2 and 5.5 years of age. Health economic analyses will be made.Ethics and disseminationThe study is conducted according to ICH/GCP guidelines and is approved by the regional ethical review board in Linköping Sweden (Dnr 2018/193-31, Dnr 2018/384-32). Results will be presented at scientific meetings and published in peer-reviewed publications.Trial registration numberThe study was registered with ClinicalTrials.gov NCT03797157, 9 January 2019.

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Characteristics of Human Breast Milk Based on Infant’s Gender

Journal of Basic and Applied Research in Biomedicine ◽

10.51152/jbarbiomed.v5i1.21 ◽

2019 ◽

Vol 5 (1) ◽

pp. 8-10

Author(s):

Moudah Alhindi ◽

Hadohum Musallam ◽

Esam Elhefian

Keyword(s):

Breast Milk ◽

Human Milk ◽

Physicochemical Properties ◽

Infant Formula ◽

Human Breast Milk ◽

Human Breast ◽

Milk Samples ◽

Complex Fluid ◽

Infant Sex ◽

Calcium And Magnesium

Human milk is a complex fluid, which contains a number of constituents such as fats, proteins and vitamins, in addition to other compounds. These nutrients are needed for infant protection against infections and diseases. This study was undertaken to evaluate some physicochemical properties and biochemical constituents content of human milk samples (based on the gender of the breast feeding infant). This includes acidity, density and viscosity, as well as lactose, protein, calcium and magnesium contents. Results showed that the highest value of viscosity as well as the highest percentages of protein and acidity were recorded for human breast milk for a boy (2.212 cP, 1.237% and 0.02% respectively) while close values for density and other biochemical contents were recorded for both types of samples. However, only the change in viscosity was found to be significant (p?0.05). Variations in some properties of human milk depending on the infant' sex could be of benefit for developing infant formula taking infant’s gender into consideration.

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Differential Transcriptional Response of Bifidobacterium longum to Human Milk, Formula Milk, and Galactooligosaccharide

Applied and Environmental Microbiology ◽

10.1128/aem.00122-08 ◽

2008 ◽

Vol 74 (15) ◽

pp. 4686-4694 ◽

Cited By ~ 66

Author(s):

Rina González ◽

Eline S. Klaassens ◽

Erja Malinen ◽

Willem M. de Vos ◽

Elaine E. Vaughan

Keyword(s):

Breast Milk ◽

Human Milk ◽

Carbohydrate Metabolism ◽

Bifidobacterium Longum ◽

Milk Formula ◽

Human Breast Milk ◽

Human Breast ◽

Dominant Group ◽

Formula Milk ◽

Carbohydrate Utilization

ABSTRACT In order to gain insight into the effects of human breast milk on the development of the intestinal bifidobacteria and associated health effects, the transcriptome of Bifidobacterium longum LMG 13197 grown in breast milk and formula milk containing galactooligosaccharides (GOS) and long-chain fructooligosaccharides was compared to that obtained in a semisynthetic medium with glucose. Total RNA was isolated from exponentially growing cells and hybridized to a clone library-based microarray. Inserts of clones with significant hybridization signals were sequenced and identified. The B. longum transcriptomes obtained during growth on human and formula milk were more similar to each other than to that obtained from growth in semisynthetic medium with glucose. Remarkably, there were only a few genes implicated in carbohydrate metabolism that were similarly upregulated during growth in both human and formula milk although oligosaccharides were added to the formula. Common highly upregulated genes notably included putative genes for cell surface type 2 glycoprotein-binding fimbriae that are implicated in attachment and colonization in the intestine. Genes involved in carbohydrate metabolism formed the dominant group specifically upregulated in breast milk and included putative genes for N-acetylglucosamine degradation and for metabolism of mucin and human milk oligosaccharides via the galactose/lacto-N-biose gene cluster. This supports the notion that the bifidogenic effect of human milk is to a great extent based on its oligosaccharides. The transcriptional effect of semisynthetic medium containing GOS, which, like human milk, contains a large amount of lactose and galactose, on the B. longum transcriptome was also studied and revealed substantial similarity with carbohydrate-utilization genes upregulated during growth in human milk. This knowledge provides leads to optimizing formula milk to better simulate the observed bifidogenic effects of human breast milk.

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Detection of SARS-CoV-2 in Human Breast Milk

10.1101/2020.04.28.20075523 ◽

2020 ◽

Cited By ~ 2

Author(s):

Rüdiger Groß ◽

Carina Conzelmann ◽

Janis A. Müller ◽

Steffen Stenger ◽

Karin Steinhart ◽

...

Keyword(s):

Breast Milk ◽

Human Milk ◽

Breast Feeding ◽

Human Population ◽

Close Contact ◽

Human Breast Milk ◽

Human Breast ◽

Milk Samples ◽

Respiratory Droplets

SARS-CoV-2 (CoV-2) is mainly transmitted in the human population during close contact and respiratory droplets. It is currently unclear, however, whether CoV-2 is shed into milk and may also be transmitted from infected mothers to newborns trough breast feeding. Two recent reviews on the topic (1,2) did not find evidence for CoV-2 in human milk. However, the number of breast milk samples analyzed so far is small and samples were taken only once from each mother (2).

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