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Immunobiology

22/04/2024

Breastfeeding confers immuno-protective factors to the baby and helps build the baby’s own lifelong immune system.

Breastfeeding is now more important than ever as optimal nutrition for the child on the one hand, and on the other hand because of its important role for the human immune system for lifelong health.

Table of Contents

IBFAN document: Breastfeeding and the immune system

Document published by IBFAN with 25 scientific references (Carol Bartle et al. 2023)

IBFAN2023-Breastfeeding-and-Immune-systemDownload

What do parents know?

Most parents are aware of the overall beneficial impact of breastfeeding on the health of the baby. Their child’s immune system is immature at birth, and few parents know that breastfeeding not only protects the child through the transfer of immunoglobulins and other immunocompetent factors, but that breast milk helps their baby to strengthen and mature his or her immune system.

Breastfeeding not only strengthens the child’s immune system, but breast milk also contributes to the child’s development. Breastfeeding provides the child with many immuno-protective factors: specific (adapted to the mother’s and child’s environment) and non-specific (those present in the basic composition of breast milk from the beginning, such as IgA, cytokines, human oligosaccharides (about 200), tumour-killing proteins, and many others – the list is long (see below).

Moreover, breastfeeding builds and nourishes the child’s microbiota. Breast milk acts on the intestinal flora and mucous membranes, two important protective filters against pathogens and viruses. As researcher Lars A. Hanson wrote as early as 2004: Breastfeeding protects the baby, and in addition, it nourishes him. Major components of human milk are not primarily for nutrition, but for host defense (see Immunobiology of Human Milk – How Breastfeeding protects babies, 2004) .

Knowledge and research into the dynamic, protective and physiological-immune role of breast milk reveal its important role and lasting impact on the health of the breastfed child – the health of the future adult.

Photograph of a bus poster in Luxemburg : To immunise my baby, I am breastfeeding

Microbiota

The microbiota is the wide variety of microorganisms that live in a certain environment: so the “human microbiota” includes all bacteria, viruses, fungi, and other single-celled organisms living in the human body. Every human body is host to anywhere between 10 trillion and 100 trillion microorganisms from over 1,000 different species. These organisms live in many different sites of the human body, such as skin, gut, mouth, lungs, and more like in breastmilk.

Breastfeeding builds and nourishes the child’s microbiota, and breast milk acts on the intestinal flora and mucous membranes, two important protective filters against pathogens and viruses. As researcher Lars A Hanson wrote as early as 2004: breastfeeding not only protects the baby, but also nourishes it: “The main components of human milk are not primarily for feeding, but for defending the baby. (in Immunobiology of Human Milk – How Breastfeeding protects babies, 2004).

Thymus

During the first two years of life, the thymus gland of the breastfed child is exceptionally large. It is the “organ” that produces T-lymphocytes or “killer” lymphocytes of infected cells and therefore plays an important role in the fight against immune aggression. In the non-breastfed child, the thymus is only half the size.

HAMLET

The protein-lipid complex HAMLET (human alpha-lactalbumin made lethal to tumor cells) has a broad spectrum of activity against cancer cells of different origin. (Ho et al. 2017)

Antiviral properties

The act of breastfeeding means more than just the nutritious transfer of human milk. It is a dynamic biological process that requires close contact between mother and baby so that the mother produces protective factors via her breast tissue in response to her environment and her own exposure to infectious agents.

Breastfeeding confers antibodies against SARS-CoV-2 virus, see the list below.

Immunoprotective factors

The following list shows immuno-protective factors that are transmittetd to the infant via breastfeeding

alpha-Lactalbumin (variant)
alpha-lactoglobulin
alpha2-macroglobulin (like)
ß-defensin-1
Bifidobacterium bifidum
Carbohydrate
Casein
CCL28 (CC-chemokine)
Chondroitin sulphate (-like)
Complement C1-C9
Folate
Free secretory component
Fucosylated oligosaccharides
Gangliosides GM1-3, GD1a, GT1b, GQ1b
Glycolipid Gb3, Gb
Glycopeptides
Glycoproteins (mannosylated)
Glycoproteins (receptor-like)
Glycoproteins (sialic acid-containing or terminal galactose)
Haemagglutinin inhibitors
Heparin
IgA secretory
IgG
IgM
IgD
kappa-Casein
Lactadherin (mucin-associated glycoprotein)
lactoferrin
Lactoperoxidase       Lewis antigens
Lipids
Lysozyme
Milk cells (macrophages, neutrophils, B & T lymphocytes)
Mucin (muc-1; milk fat globulin membrane)
Nonimmunoglobulin macromolecules (milk fat, proteins)
Oligosaccharides (about 200 human oligosaccharides are known today)
Phosphatidylethanolamine
(Tri to penta) phosphorylated beta-casein
Prostaglandins E1, E2, F2 alpha
RANTES (CC-chemokine)
Ribonuclease
Secretory IgA (see above, too)
Secretory leukocyte protease inhibitor (antileukocyte protease; SLPI)
Sialic acid-glycoproteins
sialylated oligosaccharides
Sialyllactose
Sialyloligosaccharides on sIgA(Fc)
Soluble bacterial pattern recognition receptor CD14
Soluble intracellular adhesion molecule 1 (ICAM-1)
Soluble vascular cell adhesion molecule 1 (VCAM-1)
Sulphatide (sulphogalactosylceramide)
Trypsin inhibitor
Vitamin A
vitamin B12
Xanthine oxidase (with added hypoxanthine)
Zinc

Covid-19, breastfeeding and the immune protection

Check out our specific page on Covid-19 and breastfeeding

Breastmilk Composition

What’s in Breastmilk – Poster

whatsinbreastmilkposter-2020Download

The list of immunocompetent factors transmitted from mother to child through breastfeeding is not only considerable in itself but reveals part of the way in which breastfeeding functions: it is not a static assembly of ingredients, but a biological liquid resulting from its continuous and dynamic production during breastfeeding and mother-child skin-to-skin contact.

In other words, the fine-tuned adaptation of breast milk is the result of an ongoing dialogue between the mother’s microbial environment and that of her child. Thus, in addition to the many non-specific immunological factors transmitted to the infant, the mother provides targeted anti-infective agents and immunological factors for her child.

Changes in Human Milk during prolonged lactation

The results of a study by Sinkiewicz-Darol E et al (2021) suggest an adaptive role of human milk to the nutritional needs of newborns and older children. This may support the promotion of long-term breastfeeding, including co-breastfeeding. Tandem Breastfeeding: A Descriptive Analysis of the Nutritional Value of Milk When Feeding a Younger and Older Child https://pubmed.ncbi.nlm.nih.gov/33478010/

Human milk after the 2nd year of lactation contains significantly higher concentrations of protein, SIgA, and IgG. High concentration of immunoglobulins and protein during prolonged lactation is an additional argument to support breastfeeding even after introducing solid foods and should be one of the overarching goals in the protection of children’s health. Therefore, it is important to consider when making recommendations that not even the number of feeds per day but breastfeeding, in general, should be continued for as long as possible that the mother and the baby wish to as supplement and support for the maturing immune system of the baby. Czosnykowska-Łukacka MO et al.(2020) https://doi.org/10.3389/fped.2020.00428

Lactoferrin in breastmilk. The concentration of Lf in human milk is lactation-stage related; colostrum contains more than 5 g/L, which then significantly decreases to 2-3 g/L in mature milk. The milk of mothers who are breastfeeding for more than one year is of a standard value, containing macronutrients in a composition similar to that of human milk at later stages. The aim of this study was to evaluate lactoferrin concentration in prolonged lactation from the first to the 48th month postpartum. The mean value of lactoferrin concentration was the lowest in the group of 1-12 months of lactation (3.39 ± 1.43 g/L), significantly increasing in the 13-18 months group (5.55 ± 4.00 g/L; p < 0.006), and remaining at a comparable level in the groups of 19-24 month and over 24 months (5.02 ± 2.97 and 4.90 ± 3.18 g/L, respectively). Czosnykowska-Łukacka MO et al.(2019) https://pubmed.ncbi.nlm.nih.gov/31581741/

Protein content of human milk is negatively associated to volume of milk production, so the decrease in the milk volume predicted an increase in protein content. While the nutritional content of human milk is variable, on average the milk protein concentration during the later stages of lactation is sensitive to the declining output of milk. Studies dating back several decades have shown an increase in the proportion of immunoglobulins, lactoferrin, and serum albumin during weaning or prolonged breastfeeding. Verd S et al. (2018) https://www.mdpi.com/2072-6643/10/8/1124

The aim of another study was to describe longitudinal changes in human milk macronutrient concentrations during the prolonged lactation of healthy mothers from the 1st to the 48th month. For the macronutrient content of milk of mothers breastfeeding for longer than 18 months, fat and protein increased and carbohydrates decreased significantly, compared with milk expressed by women breastfeeding up to 12 months. Moreover, the concentration of fat, protein and carbohydrates in HM over 2 years of lactation from the 24th to the 48th month remained at a stable level. Czosnykowska-Łukacka MO et al.(2018) https://pubmed.ncbi.nlm.nih.gov/30513944/

Difference between breastfeeding and feeding with human milk

There is a significant difference between

  • breastfeeding with skin to skin contact and transfer of the mother’s antibodies and the anti-infective agents in the live cells to her child, and
  • the feeding with human milk using expressed (and transformed) breastmilk and delivered through feeding apparatus. 

That said, breastmilk in any form (raw human milk, pasteurized human milk, individual donor milk or pooled breastmilk…) will always be superior to “formula” or artificial baby milk which is always at risk for contamination: on the production site (check out here) and through preparation (follow WHO Guidelines for the safe preparation, storage and handling of powdered infant formula)

Breastfeeding and epigenetics

Breastfeeding also provides epigenetic information to the child in the form of maternal stem cells, hormones and miRNA messengers which play an important role in metabolism and protection against non-communicable diseases (NCDs), known as “diseases of civilisation” (obesity, diabetes, cancer, hypertension, cardiovascular diseases…). Lancet Breastfeeding Series 2016

Ames et al. (2023) describe the broad impact of breastfeeding on the microbiota and the development of the immune system. The immune system is immature at birth. Active B and C lymphocytes can be detected in children from 12 weeks onwards, but they are much more likely to induce tolerance to antigens than to participate in the fight against pathogens. In addition, the intestinal barrier is somewhat permeable for at least the first 6 months, allowing the translocation of macromolecules such as immunoglobulins (Ig). The intestinal microbiota is established during the first few weeks, and will have a major impact on the development of the immune system, including the acquisition of oral tolerance and the establishment of defences against pathogens. A good understanding of all the factors, particularly dietary factors, that modulate all these phenomena is essential if we are to optimise them in all infants. The authors provide an overview of the subject: immune cells, enzymes and bioactive proteins, immunoglobulins, oligosaccharides, miRNA, etc. Above all, they note that: “Industrial milks contain almost none of the immunomodulating components of human milk, and they do not provide a dynamic, personalised nutritional intake.” https://pubmed.ncbi.nlm.nih.gov/37055920/

MicroRNA in human milk

“Breast milk is a complex, multiform liquid that plays an essential role in the development of infants. It is composed of water, carbohydrates, fats, proteins, vitamins and minerals, as well as numerous bioactive compounds such as hormones, oligosaccharides and immune proteins. Additionally, breast milk contains microRNAs, which have been shown to regulate gene expression and have an impact on various aspects of infant development”. Slyk-Gulewska P et al. MicroRNA as a new bioactive component in breast milk 2023, https://doi.org/10.1016/j.ncrna.2023.06.003

More than 1,400 miRNAs have been identified in human milk. Their profile depends on the mother’s diet, intestinal flora, genetic factors and the time elapsed since birth. It is likely that this profile adapts to the changing needs of the breastfed baby. These miRNAs have been associated with the modulation of the expression of more than 4,000 DNA sites involved in development and immune function. […] It appears that miRNAs are resistant to pasteurisation. Cow’s milk contains miRNAs and they have been detected in industrial milks made from cow’s milk, but at very low levels. Ames SR et al. 2023 https://pubmed.ncbi.nlm.nih.gov/37055920/

Human Breast Milk microRNAs, Potential Players in the Regulation of Nervous System : “Human breast milk (HBM) is a gold standard for preterm and term infant nutrition. It combines all essential nutrients and bioactive factors, either synthesized in the lactating breast or transferred via systemic circulation. It provides essential functions for the lactating mother and the breastfed infant. HBM composition is dynamic and may vary according to various factors related to mother, infant, environment and physiology. Among the whole variety of bioactive components, it includes miRNAs.” Freiría-Martínez L et al. 2023 https://pubmed.ncbi.nlm.nih.gov/37513702/

“Human milk is the biological fluid with the highest exosome amount and is rich in microRNAs (miRNAs). These are key regulators of gene expression networks in both normal physiologic and disease contexts, miRNAs can influence many biological processes and have also shown promise as biomarkers for disease. One of the key aspects in the regeneration of the nervous system is that there are practically no molecules that can be used as potential drugs. In the first weeks of lactation, we know that human breast milk must contain the mechanisms to transmit molecular and biological information for brain development.” Freiría-Martínez L et al. 2023 https://pubmed.ncbi.nlm.nih.gov/37513702/

“The miRNAs present in human milk come from mammary epithelial cells. Those included in the exosomes will resist digestion and can pass into the bloodstream of the breastfed baby. miRNAs have been found in many body fluids. Many of them may be present in these various fluids, and some are particularly abundant in a specific fluid. The variable profile of miRNAs in human fluids suggests that these miRNAs are selectively synthesised for each fluid. Human milk is one of the most miRNA-rich human body fluids. In contrast, industrial milks contain almost no miRNAs (whose biological activity will not necessarily be the same).” Freiría-Martínez L et al. 2023 https://pubmed.ncbi.nlm.nih.gov/37513702/

“There is accumulating evidence that milk functions as a transmitter or relay between the maternal lactation genome and epigenetic regulation of genes of the milk recipient, who under physiological conditions is the newborn infant, but under Neolithic conditions is the human consumer of bovine milk. In fact, epigenetic processes are considered to play a pivotal role in regulating tissue-specific gene expression and hence alterations in these processes can induce long-term changes in gene expression and metabolism which persist throughout life course. Because human milk protects against diseases of civilization in later life, the World Health Organization recommends exclusive breastfeeding for up to six months with continuation of breastfeeding for at least the first two years.” Melnik & Schmitz 2017, https://pubmed.ncbi.nlm.nih.gov/28933365/

Epidermal Growth Factor (EGF)

As babies gets complementary feeding, they are given increasing quantities of a variety of foods, while the volume of breast milk decreases. This leads to the formation of passage channels associated with goblet cells in the small intestine and colon. EGF could be a major regulator of the inhibition of the creation of passage channels before weaning, via its binding to goblet cells, according to studies in mice. Although there are other translocation pathways in the intestinal walls, these channels are the main route for transporting molecules present in the intestinal lumen to the lamina propria. These molecules, including bacterial and food antigens, will stimulate the local immune system and facilitate the regulation of T cells to promote antigen tolerance, with a long-term impact. This mechanism is associated with the risk of developing colitis, inflammation or intestinal cancer for the rest of one’s life. Ames et al. 2023 https://pubmed.ncbi.nlm.nih.gov/37055920/

Bibliography (chronological)

Risks of artificial feeding

The risks of formula feeding are essentially depriving the child of the many benefits provided by breast milk. For information on the benefits of breastfeeding, see The Lancet Breastfeeding Series 2016. In terms of regulating short and long-term health, keep in mind that “Industrial milks contain almost none of the immunomodulatory components of human milk, and they do not provide a dynamic, personalised nutritional intake.” See above, Ames SR et al. 2023 https://pubmed.ncbi.nlm.nih.gov/37055920/

These risks are known for a long time. The following document by Dr Jack Newman lists research items about the negative impact of articifial feeding as of 1998.

Dr-Newman-Risks-of-Artificial-Feeding-1998Download