Talk:Normal Development - Milk

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Cite this page: Hill, M.A. (2019, September 22) Embryology Normal Development - Milk. Retrieved from

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Maternal Milk

<pubmed limit=10>Maternal Milk</pubmed>

Mammalian Milk

<pubmed limit=10>Mammalian Milk</pubmed>


<pubmed limit=10>Milk</pubmed>


Innate Immunity and Breast Milk

Front Immunol. 2017 May 29;8:584. doi: 10.3389/fimmu.2017.00584. eCollection 2017.

Cacho NT1, Lawrence RM2.


Human milk is a dynamic source of nutrients and bioactive factors; unique in providing for the human infant's optimal growth and development. The growing infant's immune system has a number of developmental immune deficiencies placing the infant at increased risk of infection. This review focuses on how human milk directly contributes to the infant's innate immunity. Remarkable new findings clarify the multifunctional nature of human milk bioactive components. New research techniques have expanded our understanding of the potential for human milk's effect on the infant that will never be possible with milk formulas. Human milk microbiome directly shapes the infant's intestinal microbiome, while the human milk oligosaccharides drive the growth of these microbes within the gut. New techniques such as genomics, metabolomics, proteomics, and glycomics are being used to describe this symbiotic relationship. An expanded role for antimicrobial proteins/peptides within human milk in innate immune protection is described. The unique milieu of enhanced immune protection with diminished inflammation results from a complex interaction of anti-inflammatory and antioxidative factors provided by human milk to the intestine. New data support the concept of mucosal-associated lymphoid tissue and its contribution to the cellular content of human milk. Human milk stem cells (hMSCs) have recently been discovered. Their direct role in the infant for repair and regeneration is being investigated. The existence of these hMSCs could prove to be an easily harvested source of multilineage stem cells for the study of cancer and tissue regeneration. As the infant's gastrointestinal tract and immune system develop, there is a comparable transition in human milk over time to provide fewer immune factors and more calories and nutrients for growth. Each of these new findings opens the door to future studies of human milk and its effect on the innate immune system and the developing infant. KEYWORDS: breast milk; colostrum; human milk; innate immunity; preterm PMID: 28611768 PMCID: PMC5447027 DOI: 10.3389/fimmu.2017.00584


The Effect of UV-C Pasteurization on Bacteriostatic Properties and Immunological Proteins of Donor Human Milk

Lukas Christen Ching Tat Lai, Ben Hartmann, Peter E. Hartmann, Donna T. Geddes

Published: December 23, 2013DOI: 10.1371/journal.pone.0085867


UV-C irradiation of human milk preserves significantly higher levels of immunological proteins than Holder pasteurization, resulting in bacteriostatic properties similar to those of untreated human milk.


Colostrum of healthy mothers contains broad spectrum of secretory IgA autoantibodies

J Clin Immunol. 2012 Dec;32(6):1372-80. doi: 10.1007/s10875-012-9733-9. Epub 2012 Jul 10.

Pribylova J, Krausova K, Kocourkova I, Rossmann P, Klimesova K, Kverka M, Tlaskalova-Hogenova H. Source Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20, Prague 4-Krč, Czech Republic.


PURPOSE: Human colostrum and milk provide a newborn with immunomodulatory components, ensuring protection and proper development of the immune system. Secretory IgA antibodies in colostrum represent the first line of defence against harmful substances, but their potential spectra of reactivity with autoantigens remains unclear. Here, we characterised the repertoire of natural sectretory IgA autoantibodies in colostrum of healthy mothers. METHODS: The human colostrum samples from 39 healthy mothers were analyzed for autoantibodies by indirect immunofluorescence, dot blots, immunoblots and ELISA. RESULTS: We found that there is high diversity in reactivities of colostral IgA antibodies to autoantigens among individual samples. Using tissue sections and biochips commonly used for autoimmunity testing, we found that most samples reacted with monkey ovary (79.3 %), monkey pancreatic tissue (78.6 %), human HEp-2 cells (69 %) and monkey adrenal gland (69.0 %), fewer samples reacted with monkey liver tissue (47.2 %), rat stomach (42.9 %), monkey testicular tissue (41.4 %), monkey salivary gland (39.3 %), rat kidney (32.1 %) and monkey cerebellar tissue (17.9 %). At the protein level, we detected reactivity of IgA with 21 out of 25 (auto) antigens. The majority of the samples reacted with the pyruvate dehydrogenase complex, E3 ubiquitin ligase, cytosolic liver antigen, promyelocytic leukemia protein and nuclear pore glycoprotein-210. Using ELISA, we found reactivity of colostral IgA antibodies against examined extractable nuclear antigens, double stranded DNA, phospholipids and neutrophil cytoplasm. CONCLUSIONS: The broad spectrum of polyreactive natural autoantibodies present in human colostrum may contribute to proper development of mucosal immune system of the breastfed infant.

PMID 22777159

The human milk microbiota: Origin and potential roles in health and disease

Pharmacol Res. 2012 Sep 10. pii: S1043-6618(12)00165-X. doi: 10.1016/j.phrs.2012.09.001. [Epub ahead of print]

Fernández L, Langa S, Martín V, Maldonado A, Jiménez E, Martín R, Rodríguez JM. Source Department of Nutrition, Food Science and Food Technology, Complutense University of Madrid, 28040 Madrid, Spain.


Human milk has been traditionally considered sterile; however, recent studies have shown that it represents a continuous supply of commensal, mutualistic and/or potentially probiotic bacteria to the infant gut. Culture-dependent and -independent techniques have revealed the dominance of staphylococci, streptococci, lactic acid bacteria and bifidobacteria in this biological fluid, and their role on the colonization of the infant gut. These bacteria could protect the infant against infections and contribute to the maturation of the immune system, among other functions. Different studies suggest that some bacteria present in the maternal gut could reach the mammary gland during late pregnancy and lactation through a mechanism involving gut monocytes. Thus, modulation of maternal gut microbiota during pregnancy and lactation could have a direct effect on infant health. On the other hand, mammary dysbiosis may lead to mastitis, a condition that represents the first medical cause for undesired weaning. Selected strains isolated from breast milk can be good candidates for use as probiotics. In this review, their potential uses for the treatment of mastitis and to inhibit mother-to-infant transfer of HIV are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID 22974824


Breast milk hormones and regulation of glucose homeostasis

Int J Pediatr. 2011;2011:803985. Epub 2011 May 5.

Savino F, Liguori SA, Sorrenti M, Fissore MF, Oggero R. Source Department of Pediatrics, Regina Margherita Children's Hospital, University of Turin, 10126 Turin, Italy.


Growing evidence suggests that a complex relationship exists between the central nervous system and peripheral organs involved in energy homeostasis. It consists in the balance between food intake and energy expenditure and includes the regulation of nutrient levels in storage organs, as well as in blood, in particular blood glucose. Therefore, food intake, energy expenditure, and glucose homeostasis are strictly connected to each other. Several hormones, such as leptin, adiponectin, resistin, and ghrelin, are involved in this complex regulation. These hormones play a role in the regulation of glucose metabolism and are involved in the development of obesity, diabetes, and metabolic syndrome. Recently, their presence in breast milk has been detected, suggesting that they may be involved in the regulation of growth in early infancy and could influence the programming of energy balance later in life. This paper focuses on hormones present in breast milk and their role in glucose homeostasis.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PMID 21760816

Premature Delivery Influences the Immunological Composition of Colostrum and Transitional and Mature Human Milk

J Nutr. 2011 Apr 20. [Epub ahead of print]

Castellote C, Casillas R, Ramírez-Santana C, Pérez-Cano FJ, Castell M, Moretones MG, López-Sabater MC, Franch A. Source Department of Physiology, Faculty of Pharmacy, University of Barcelona, Barcelona 08028, Spain. Abstract Human breast milk is the ideal nutrition for the newborn, and in addition to its nutritional contribution, necessary for infant growth and development, it contains various immune bioactive factors that confer some of the numerous beneficial effects of breastfeeding. The current study analyzed the concentrations of IgA, growth factors such as epidermal growth factor (EGF), TGFβ1, and TGFβ2, cytokines IL-6, IL-8, IL-10, IL-13, and TNFα, and TNF-receptor I (TNF-RI) in colostrum and transitional and mature milk from mothers with mature, premature, and very premature infants. Human milk samples were collected from mothers delivering at term (T), preterm (PT), and very preterm (VPT). Milk from all the mothers was collected at 3 different time points after delivery corresponding to colostrum and transitional and mature milk. After obtaining milk whey, IgA, EGF, TGFβ1, and TGFβ2 were determined by ELISA and IL-6, IL-8, IL-10, IL-13, TNFα and TNF-RI by cytometric bead array immunoassay. The colostrum of the PT group was extremely rich in most of the factors studied, but higher concentrations than in the T group were only found for IL-6 (P = 0.051), TGFβ1, and TGFβ2 (P < 0.05). Conversely, the colostrum of the VPT group had lower concentrations of IgA, IL-8, IL-10, and TNFα than those in the T group (P < 0.05). Results suggest that maternal lactogenic compensatory mechanisms accelerating the development of immature breast-fed preterm infants may take effect only after wk 30 of gestation.

PMID 21508211

Breastmilk cultures and infection in extremely premature infants

J Perinatol. 2011 May;31(5):335-8. Epub 2011 Feb 24.

Schanler RJ, Fraley JK, Lau C, Hurst NM, Horvath L, Rossmann SN. Source 1] Division of Neonatal-Perinatal Medicine, Cohen Children's Medical Center of New York at North Shore, North Shore University Hospital, Manhasset, NY, USA [2] Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA.


Objective:As expressed mother's milk (MM) is known to be colonized by microbial species, it is occasionally considered as a source of infection in premature infants, prompting some clinicians to obtain milk bacterial culture results before infant feeding. To determine whether serial microbial cultures of MM predict infection in premature infants.Study Design:Milk microbial flora was determined by plate counts from aliquots of MM obtained from 161 mothers of infants born <30 weeks gestation (n=209). Pathogens isolated from the same infant were tabulated.Result:Milk samples (n=813) yielded 1963 isolates. There were no relationships between microbial counts and maternal age, ethnicity, education, skin-to-skin contact and infant infection. In 64 infants, milk and pathological isolates had presumptively the same Gram-positive organism, yet the odds of infection before or after exposure to milk containing that Gram-positive organism were not significant (1.18; 95% confidence interval=0.51, 2.76). In eight infants, milk and pathological isolates had presumptively the same Gram-negative organism, which appeared sporadically in milk, either before or after isolation in the infant.Conclusion:Results of initial milk cultures do not predict subsequent culture results. Random milk cultures, even if obtained at any time during hospitalization, are not predictive of infection in premature infants. The sporadic nature of the appearance of certain isolates, however, suggests common exposure of both mother and infant. Routine milk cultures do not provide sufficient data to be useful in clinical management.

PMID: 21350430

Breastfeeding and body composition in children: will there ever be conclusive empirical evidence for a protective effect against overweight?

Am J Clin Nutr. 2011 Apr 27. [Epub ahead of print]

Beyerlein A, von Kries R. Source Institute of Social Paediatrics and Adolescent Medicine, Ludwig-Maximilians University of Munich, Munich, Germany.


An increased prevalence of childhood overweight has been observed worldwide over the past decades, which indicates the need for strategies to prevent obesity. There is some evidence that risk of obesity is primed by exposures early in life. Among other factors, breastfeeding has been hypothesized as a potential priming factor against overweight. Although the properties of human milk suggest possible mechanisms for a protective effect of breastfeeding compared with formula feeding with respect to later overweight, empirical evidence is more difficult to establish. This article reviews the available epidemiologic literature on this topic. Several observational studies have shown evidence for a small protective effect with respect to overweight in childhood. Three meta-analyses reported significant protective effects of breastfeeding against overweight in later life, whereas another meta-analysis showed no effect of breastfeeding on mean body mass index (BMI) after adjustment for confounding factors. These seemingly inconsistent results might potentially be explained by different effects of breastfeeding in normal-weight compared with overweight children. Evidence from interventional studies is limited. A randomized trial failed to confirm an effect of a breastfeeding promotion on children's BMI, but this trial lacked statistical power because rates of breastfeeding were relatively similar in the intervention and control groups. In conclusion, protective priming effects of breastfeeding on later overweight appear to be possible but are difficult to prove. Although observational studies have to deal with confounding issues, interventional studies on breastfeeding promotion may lack power.

PMID 21525195

COMPANION ANIMALS SYMPOSIUM: Development of the mammalian gastrointestinal tract, the resident microbiota, and the role of diet in early life

J Anim Sci. 2011 May;89(5):1506-19. Epub 2011 Jan 14.

Buddington RK, Sangild PT. Source Department of Health and Sport Science, University of Memphis, Memphis, TN 38152.


Mammalian gastrointestinal (GI) development is guided by genetic determinants established during the evolution of mammals and matched to the natural diet and environment. Coevolution of the host GI tract (GIT) and the resident bacteria has resulted in commensal relationships that are species and even individual specific. The interactions between the host and the GI bacteria are 2-way and of particular importance during the neonatal period, when the GIT needs to adapt rapidly to the external environment, begin processing of oral foods, and acquire the ability to differentiate between and react appropriately to colonizing commensal and potentially pathogenic bacteria. During this crucial period of life, the patterns of gene expression that determine GI structural and functional development are modulated by the bacteria colonizing the previously sterile GIT of fetuses. The types and amounts of dietary inputs after birth influence GI development, species composition, and metabolic characteristics of the resident bacteria, and the interactions that occur between the bacteria and the host. This review provides overviews of the age-related changes in GIT functions, the resident bacteria, and diet, and describes how interactions among these 3 factors influence the health and nutrition of neonates and can have lifelong consequences. Necrotizing enterocolitis is a common GI inflammatory disorder in preterm infants and is provided as an example of interactions that go awry. Other enteric diseases are common in all newborn mammals, and an understanding of the above interactions will enhance efforts to support neonatal health for infants and for farm and companion animals.

PMID 21239667


Bioactive proteins in human milk: mechanisms of action

J Pediatr. 2010 Feb;156(2 Suppl):S26-30.

Lönnerdal B. Source Department of Nutrition, University of California, Davis, CA, USA.


Human milk contains a multitude of bioactive proteins, with very diverse functions. Some of these proteins are involved in the synthesis and expression of milk, but the majority appears to have evolved to provide physiological activities in the breast-fed infant. These activities are exerted by a wide variety of mechanisms and have largely been unraveled by in vitro studies. To be active in the gastrointestinal tract, these proteins must be able to resist proteolytic degradation, at least for some time. We have evaluated the human milk proteins lactoferrin, haptocorrin, alpha(1)-antitrypsin, and transforming growth factor -beta in an in vitro digestion model, mimicking the conditions of the infant gastrointestinal milieu. These bioactive proteins are resistant against proteolysis and can remain intact or as larger fragments through passage of the gastrointestinal tract. In vitro digestibility assays can be helpful to assess which human milk proteins can resist proteolysis and to what extent.

Copyright 2010 Mosby, Inc. All rights reserved.

PMID: 20105661

Lead levels in human milk and children's health risk: a systematic review

Rev Environ Health. 2010 Jul-Sep;25(3):243-53. Koyashiki GA, Paoliello MM, Tchounwou PB. Source Department of Collective Health, Health Science Center, State University of Londrina, Parana, Brazil.


Lead (Pb), a naturally-occurring element and industrially-produced metal, is highly toxic to children, causing intellectual and behavioral deficits, hyperactivity, fine motor function deficits, decreased intelligence quotient, alteration of hand-eye coordination, and problems in reaction time. Children's exposure to Pb occurs mainly through ingestion of contaminated food, water and soil. Few discussions have been held on the magnitude and potential risk associated with exposure from the consumption of breast milk. Hence, this research was designed to systematically review the scientific literature on published epidemiologic studies, with an emphasis on the study designs and analytical procedures used for Pb assessment in breast milk. From a total of 112 selected articles published since the 1980s, 11 met the inclusion criteria. A review of the data indicated that Pb levels varied from 0.15 to 6.1 microg L(-1) in mature milk samples, from 0.48 to 14.6 microg L(-1) in colostrum samples, and were non-detectable in some samples. The milk/blood ratio, which estimates the mean efficiency transfer of lead from blood to milk, varied between 0.01 and 0.48. The heterogeneity of methods revealed by our assessment of published studies underscores the need for harmonization of study designs and sample collection and analysis protocols to reflect specific exposure scenarios. Human milk seems to be one of the relevant biological matrices for use as a biomarker for assessing children's health risk to Pb poisoning.

PMID 21038758


Reevaluation of the DHA requirement for the premature infant

Prostaglandins Leukot Essent Fatty Acids. 2009 Aug-Sep;81(2-3):143-50. Epub 2009 Jul 5.

Lapillonne A, Jensen CL. Source APHP, Paris Descartes University, Paris, France.


The long-chain polyunsaturated fatty acid (LC-PUFA) intake in preterm infants is crucial for normal central nervous system development and has the potential for long-lasting effects that extend beyond the period of dietary insufficiency. While much attention has focused on improving their nutritional intake, many premature infants do not receive an adequate DHA supply. We demonstrate that enterally fed premature infants exhibit daily DHA deficit of 20mg/kg.d, representing 44% of the DHA that should have been accumulated. Furthermore, the DHA content of human milk and current preterm formulas cannot compensate for an early DHA deficit which may occur during the first month of life. We recommend breast-feeding, which supplies preformed LC-PUFA, as the preferred method of feeding for preterm infants. However, to fulfill the specific DHA requirement of these infants, we recommend increasing the DHA content of human milk either by providing the mothers with a DHA supplement or by adding DHA directly to the milk. Increasing the DHA content above 1% total fatty acids appears to be safe and may enhance neurological development particularly that of infants with a birth weight below 1250 g. We estimate that human milk and preterm formula should contain approximately 1.5% of fatty acid as DHA to prevent the appearance of a DHA deficit and to compensate for the early DHA deficit.

PMID 19577914


Evolution of lactation: nutrition v. protection with special reference to five mammalian species

Nutr Res Rev. 2008 Dec;21(2):97-116. McClellan HL, Miller SJ, Hartmann PE. Source School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley WA 6009, Australia.


The evolutionary origin of the mammary gland has been difficult to establish because little knowledge can be gained on the origin of soft tissue organs from fossil evidence. One approach to resolve the origin of lactation has compared the anatomy of existing primitive mammals to skin glands, whilst another has examined the metabolic and molecular synergy between mammary gland development and the innate immune system. We have reviewed the physiology of lactation in five mammalian species with special reference to these theories. In all species, milk fulfils dual functions of providing protection and nutrition to the young and, furthermore, within species the quality and quantity of milk are highly conserved despite maternal malnutrition or illness. There are vast differences in birth weight, milk production, feeding frequency, macronutrient concentration, growth rate and length of lactation between rabbits, quokkas (Setonix brachyurus), pigs, cattle and humans. The components that protect the neonate against infection do so without causing inflammation. Many protective components are not unique to the mammary gland and are shared with the innate immune system. In contrast, many of the macronutrients in milk are unique to the mammary gland, have evolved from components of the innate immune system, and have either retained or developed multiple functions including the provision of nourishment and protection of the hatchling/neonate. Thus, there is a strong argument to suggest that the mammary gland evolved from the inflammatory response; however, the extensive protection that has developed in milk to actively avoid triggering inflammation seems to be a contradiction.

PMID 19087365

The nutritional modulation of the evolving intestine

Berni Canani R, Passariello A, Buccigrossi V, Terrin G, Guarino A. Source Department of Pediatrics, University Federico II of Naples, Naples, Italy. Abstract Nutrition plays a major role in the modulation of the evolving human gut influencing all the main components of the intestinal ecosystem. The regulatory role of nutrition is particularly crucial in the early postnatal period but it continues also in subsequent ages when the development of the gastrointestinal tract is completed. Recent data support the hypothesis that nutrition can affect some inherited disorders of gastrointestinal tract. These "epigenetic" mechanisms are involved in the development of intestinal enzymes, hormones, transporters, and immunity. This is an expanding research area related to the possible nutritional intervention in selected clinical condition. This paper is focused on the main components and mechanisms of action of the nutritional modulation on intestinal development.

PMID 18685515 J Clin Gastroenterol. 2008 Sep;42 Suppl 3 Pt 2:S197-200.


Transfer of antibody via mother's milk

Vaccine. 2003 Jul 28;21(24):3374-6.

Van de Perre P. Source Laboratory of Bacteriology and Virology, University Hospital A. de Villeneuve and Mixed Research Unit 145 (UMR 145), Institute for Research and Development (IRD) and University of Montpellier 1, Montpellier, France.


Differing from humans, IgG from breast milk in many animal species (rodents, bovines, cats, ferrets, etc.) are transported across the intestinal epithelium into the neonatal circulation. This transport is located at the duodenal and jejunal level where enterocytes express a surface membrane receptor able to bind Fc of IgG and to facilitate transcytosis of these immunoglobulins. Fcgamma-R, which is very similar to the placenta receptor responsible for active transplacental transfer of IgG in humans, binds IgG but not other isotypes. Maternal milk antibodies represent an important part of circulating IgG in these animals, as they are involved in the negative feedback of endogenous IgG synthesis. This phenomenon stops abruptly as soon as weaning takes place. Neonatal calves that have a defect in such transfer of maternal immunoglobulins are at high risk of systemic infectious diseases. In humans, in whom gut closure occurs precociously, breast milk antibodies do not enter neonatal/infant circulation. A large part of immunoglobulins excreted in milk are IgA that protect mainly against enteric infections. The specificity of maternal milk IgA is driven by an entero-mammary cell circulation. Human milk also contains anti-idiotypic antibodies capable of enhancing infant antibody response. Maternal milk antibodies coat infant mucosal surfaces and some have a clear protective role. This has been studied extensively in infectious disease models such as rotavirus, E. coli, poliovirus, and retroviruses. In the rotavirus model, antirotaviral IgA can be detected in stools of breast-fed but not bottle-fed neonates. In a large cohort of lactating women infected with HIV-1 in Rwanda, anti-HIV milk antibodies of the IgG isotype were more frequently detected followed by secretory IgM. Surprisingly, anti-HIV-1 SIgA were less frequently found. The presence of milk SIgA at 15 days as well as the persistence of a SIgM response during the whole lactation period was associated with lower risk of HIV transmission from the mother to the infant. Recently, HIV-1 antibodies from maternal milk have been shown to block transcytosis in vitro in a monolayer enterocyte model. Among these antibodies, those directed against the ELDKWA epitope had higher neutralising activity than serum antibodies. In humans, milk excreted antibodies play a major role in protecting infants from infection by pathogens having a mucosal portal of entry.

PMID: 12850343



Intestinal absorption of immunoglobulins by newborn infants

Arch Dis Child. 1972 Jun;47(253):411-4.

Iyengar L, Selvaraj RJ.

Intestinal absorption in newborn infants of immunoglobulins present in colostrum was studied by measuring the concentrations of immunoglobulins IgA, IgG, and IgM in cord blood and following the changes in the serum of the infant on the 5th day after birth. In infants who did not receive colostrum, a marked fall in IgG levels was observed on the 5th day after birth as compared to levels at birth. The concentrations of IgA and IgM showed marginal changes. In contrast, colostrumfed infants showed significant increases in the concentration of IgG. Levels of all 3 immunoglobulins on the 5th day were significantly higher in the serum of colostrumfed infants as compared to those who did not receive colostrum. It is suggested that immunoglobulins present in colostrum are to some extent absorbed from the intestinal tract of newborn infants, and this may have some physiological significance in the resistance to infection during the early neonatal period.

PMID 4624594