Immunology of Breast Milk

Science and technology have elucidated important information about neonates and infants’ applications and benefits from breast milk’s immunology. Nevertheless, breastfeeding and lactation always had healing and sometimes (called) magical powers associated with them.

Human milk and breastfeeding are important parts of community health. Also, historically human milk was linked to miracles, such as the one involving St. Bernard, in which human milk healed his eye infection in addition to giving the gift of great wisdom.

Human milk components:

The wealth of biologically active components that human milk provides to the suckling neonate have proven to be effective and essential to human development and survival. The main products of human lactation are colostrum and milk. They provide immunologic and microbiological protection mediated by the mother’s prior experiences. Furthermore, the main biologically active components are Secretory IgA, nutritional components, hormones, cytokines and chemokines, casein, polysaccharides, oligosaccharides, and lipids.

The historical science of breast milk’s immunology started with Dr. Lars Hanson and Gugler and von Muralt. In fact, the discovery of secretory IgA (SIgA) was followed by identifying multiple soluble and cellular immunologic elements in breast milk and how it was transported to the neonate by breastfeeding. More recently, information about the immunologic activity attributed to the biologically active products in human milk and their function on the mucosal immune system has been present in multiple studies.

Immunology of human milk:

Milk’s active immunological products are:

1.- Secreted and synthesized by the mammary glands.

2.- All the compounds and products depend directly on the maternal bloodstream and circulation.

3.- These compounds are transported, selectively and specifically, from the mucosa-associated lymphoid tissue located in multiple sites such as nasopharynx, bronchoepithelial mucosal sites, and sublingual lymphoid tissue.

Colostrum is the product to be secreted by the mammary glands after birth. Its composition is described by being dense in protein and fat as well as immunologic components. On the other hand, mature milk has less protein, fat, and it has been reported to have a decreased number of immunologic components. In fact, these diminished amounts of immune factors are mainly associated with the fact that the infant has developed a better immunologic response. Also, the secretion of mature milk is orchestrated by many factors, including endocrine signaling, maternal-infant stimulation, and neural interactions. These actions will contribute to the stimulation of neural pathways needed to maintain prolactin and oxytocin.

Soluble components

Immunoglobulins:

As mentioned before, immunoglobulins levels have been reported to decrease or change depending on the lactation time. The highest levels of SIgA and IgG are observed during the first 3-5 days of lactation. Also, IgA levels are 4-5 times higher than IgM and 26-30 times higher than IgG levels. Besides, there are multiple isotypes of SIgA: 11SIgA is one of the major isotypes, followed by 7SIgA, IgG, IgM, and IgG, while IgE is occasionally observed.

11SIgA is a dimer composed of 2 molecules of 7SIgA by a polypeptide chain associated with a secretory component. Furthermore, observational studies have found that IgA levels drop rapidly as lactation progresses, but an increased amount of milk production compensates. Also, it is reported that a fully breastfed infant ingests 1g of IgA per day.

In terms of reactivity, studies involving the actions of IgA and microorganisms like Escherichia coli 083 and Streptococcus pneumoniae show that IgA levels in milk rise independently from serum levels. Furthermore, this shows an enteromammary and bronchomammary axis, and when exposed to antigens, it promotes the IgA secretion into the mammary glands.

Antisecretory factor:

This hormone-like factor binds to certain polysaccharides and is produced by many tissues, including the mammary glands. Furthermore, this compound has been found in human milk in poor socioeconomic settings, possibly induced by enterotoxin- producing bacteria. Antisecretory factor beneficial effects include anti-inflammation; it has been useful on diarrhea reduction and inflammatory bowel disease.

Soluble CD14 and Soluble Toll-Like Receptor.

The function of colostrum´s CD14 has been associated with its binding action to lipopolysaccharides and allowing a better cleavage to the TLR-4 receptor and posterior phagocyte activation, showing that milk’s CD14 activates gut mucosal phagocytes in the presence of gram-positive and gram-negative organisms.

Cytokines.

Over 150 cytokines have been previously identified in human milk. Furthermore, the different immunomodulating roles of cytokines are:

1.- Growth and differentiation of immunoglobulin products of B cells.

2.- Promotion of thymocyte proliferation.

3.- Suppression of IgE production.

4.- Inhibition of IL-2 production by T cells.

Chemokines

These are described as specific and selective small cytokines; they serve as signaling to mobilize phagocytes to an inflamed area. One of these chemokines found in human milk is IL-8.

IL-7 has also been recovered from human milk. This growth factor is involved in thymic growth and, therefore, the enhancement of the individual’s immunological response.

Cellular components:

Leukocytes:

These elements are found in colostrum and early milk in 1–3 × 106 leukocytes/mL, sometimes even more. Conversely, these levels seem to decline gradually with the continuation of breastfeeding, and they can go as low as <1 × 106/mL over the next 2–3 months of lactation. Also, in the presence of maternal infection, milk leukocyte levels are known to increase until the infection is resolved.

Macrophages:

Milk macrophages show various functional and phenotypic characteristics, such as producing cytokines like IL-1?, IL-6, TNF-?, and GM-CSF. Nevertheless, macrophages can provide antigen presentation and can synthesize plasminogen activator, lysozyme, prostaglandin E_2, and C3.

Epithelial cells:

Cells from the milk ducts, myoepithelial cells, and alveolar epithelial cells can be found in the colostrum. Therefore, this shows that epithelial cells found in the colostrum are detached from the mammary glands’ stroma. Additional studies to determine the function that these epithelial cells have on the infant’s health are needed.

Stem cells and lymphocytes are commonly found in human milk. In fact, stem cells have shown cell differentiation properties in milk and can turn into cells of other lineages like hepatocytes, adipocytes, and pancreatic B-cells. On the other hand, compared to the large number of leukocytes found in milk, lymphocytes account for about 4-6% of the total cells.

In conclusion: the benefits of breastfeeding

In conclusion, human milk has beneficial immune properties, and these properties are specific to the infant’s needs. Also, colostrum’s important features and its components make the neonate the most important vehicle of immunologic protection. Nevertheless, there are still numerous bioactive compounds found in human milk that need further studies. In order to provide a better and tailored diet to pregnant women, DNA tests can be used.

Healthy diet, healthy genes:

After reading all of this interesting information you might feel a little confused about what to do to improve your genetic code. I mean, that idea would definitely be on my mind if I was pregnant. Since studies show that maternal immunity can infuence neonate immunological reactions and everything is linked to gut permeability, I will provide you some options to change your daily gluten intake and improve your dietary fiber:

• Millet
• Quinoa
• Oats
• Rice (basmati, bran, brown, wild)
• Rye
• Amaranth
• Tapioca
• Corn
• Kamut
• Teff

-Ana Paola Rodríguez Arciniega. Master in Clinical Nutrition

References:

Baldassarre, Maria Elisabetta, et al. “Administration of a multi-strain probiotic product to women in the perinatal period differentially affects the breast milk cytokine profile and may have beneficial effects on neonatal gastrointestinal functional symptoms. A randomized clinical trial.” Nutrients 8.11 (2016): 677.

Ogra, Pearay L. “Immunology of Human Milk and Lactation: Historical Overview.” Milk, Mucosal Immunity, and the Microbiome: Impact on the Neonate. Vol. 94. Karger Publishers, 2020. 11-26.

Dr. Alex Jimenez’s Blog Post

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