Epigenetics of Breastfeeding: 4 Diseases and Disorders That Breast Milk Could Protect Against

breastfeeding baby epigenetic benefits

Many people believe that breastfeeding is the best gift a mother can offer to her child. It has lots of benefits, not only because breast milk contains the right amount of nutrients, but also because it’s packed with lots of antibodies and biologically active compounds that play a key role in boosting a baby’s immune system.

We have already seen how maternal nutrition and lifestyle can shape the development and future health of a baby via epigenetic mechanisms. Among many postnatal factors that can contribute to determining lifelong health and disease through epigenetic mechanisms, infant feeding plays a key role, especially breastfeeding.

Breast milk has been shown to protect newborns against many diseases commonly experienced during the first year of life and research has begun to make connections between the benefits of breastfeeding and epigenetics.1 In the spirit of World Breastfeeding Week, we’ll explore the health benefits of breastfeeding, the possible epigenetic effects, and its potential ability to protect against four major diseases.

Health Benefits Associated With Breastfeeding

baby and mother epigenetics of breastfeeding
Breastfeeding has been connected to numerous health benefits and reduced disease risk for the child.

Human milk confers unique nutritional and non-nutritional benefits, enhancing a child’s growth and development, as well as overall health, not only in early life but also for the long-term, and offering prevention against some diseases.

Recently, studies have confirmed that breastfeeding reduces the risk of hospitalization for lower respiratory tract infections in the first year; it also lowers the incidence of otitis media – a group of inflammatory diseases of the middle ear – and ear or throat infections.

Breast milk has also proved to have a protective effect in reducing the occurrence of gastrointestinal problems, asthma, atopic dermatitis, and eczema. In addition, the rates of celiac disease, inflammatory bowel disease, obesity, and diabetes are also lower in people who were breastfed, not to mention the positive effects of human milk feeding on long-term neurodevelopment.2,3

Epigenetic Effects of Breastfeeding

With these health benefits in mind, researchers have been exploring the potential underlying epigenetic mechanisms that may be linked to the benefits of breastfeeding.

An epigenetic mechanism is a biochemical alteration to the DNA that does not change the sequence but does influence gene expression. These epigenetic alterations are greatly influenced by the environment and are heritable.4 The major epigenetic processes are DNA methylation, histone modification, and chromatin remodeling.

To date, most studies on the effect of early-life nutrition, including breastfeeding, on the epigenetic regulation of genes have focused on modifications of the DNA methylation pattern, one of the most popular epigenetic marks to study. Early nutrition can influence DNA methylation because one-carbon metabolism is dependent on dietary methyl donors and cofactors, including methionine, choline, folic acid, and vitamin B12. 1,5

Here are 4 main diseases and disorders that breast milk may epigenetically protect against:

1. Inflammatory Bowel Disease

Neonatal necrotizing enterocolitis (NEC) is a devastating inflammatory bowel disease that affects mostly premature infants or those who were born at less than 37 weeks gestational age.6 When children are fed with human milk instead of artificial formula, the occurrence of NEC is much lower. This might be explained by the gut microbiota which can be altered by many factors in early age. Notably, these perturbations can play a role in the susceptibility to several diseases by modulating the immune development through epigenetic modifications. 1,2,7,12

When babies are breastfed, human breast milk components promote a healthier gut bacteria, which regulate the expression of genes involved in digestion, barrier function, and production of secretory IgA (sIgA). sIgA is the most abundant class of antibody in our organism and plays a crucial role in the immune function of mucous membranes and protection against pathogenic organisms. Moreover, sIgA positively influences the gut microbiota composition. Breastfeeding adjusts the composition of the gut microbiota, which then impacts DNA methylation.

Alterations in intestinal DNA methylation may contribute to high NEC susceptibility in preterm babies. A study revealed that infants’ intestines undergo rapid changes in DNA methylation during the first days after birth, with more dramatic changes occurring when babies are initially fed with infant formula, not mother’s milk. The resulting hypermethylation may likely induce long-lasting effects beyond the neonatal period.8

Bacteria within our gut regulate the expression of genes important for digestion. Our friendly bacteria can also inhibit the nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB),  which is  a crucial transcription factor that participates in inflammatory response and many other physiological and pathological conditions, including immune response, apoptosis, and carcinogenesis.9 If the NF-κB pathway is inhibited by human breast milk, it’ll suppress proinflammatory cytokines genes, such as interleukin-8 (IL-8), interleukin-1 (IL-1), and tumor necrosis factor (TNF).10

Ultimately, breastfeeding may play a role in preventing NEC by programming sIgA excretion through the influence on gut microbiota composition.11,12

2. Disorders of the Immune System

baby protected from immune related disorders via epigenetics of breastmilk
Breast milk could epigenetically protect a child from immune-related diseases by influencing the gut microbiota.

Breastfeeding has been shown to help prevent infections and other immune-related illnesses, particularly gastrointestinal infections and acute otitis media, even if the child has genetic susceptibility.3 The proposed mechanisms are similar to those for NEC, where the gut microbiota epigenetically mediates the expression of proinflammatory cytokines genes.

Furthermore, human milk contains oligosaccharides which promote healthier gut bacteria, which plays a leading role in epigenetically programming the infant’s immune phenotype and infection susceptibility.1,12

Overall, research suggests that breastfeeding may be able to epigenetically provide resistance against disorders of the immune system by influencing the gut microbiota, which influences proinflammatory genes.

3. Obesity and Related Disorders

Obesity is probably the disorder with the most remarkable evidence about nutritional programming and the protective effects of breastfeeding, due to a wide range of mechanisms, including epigenetic regulation.13,14 As we know, obesity is a multifactorial disease – it’s the result of the interaction between genetics, environment and individual lifestyles, including feeding practices during the early ages of life.

Babies fed with artificial formula can develop intestinal dysbiosis which leads to an unhealthy epigenetic expression. It is well known that gut microbiota has an important role in human metabolism – an unbalanced microbiota would be a risk factor for a child developing obesity.15

Researchers have also suggested that breastfeeding is negatively associated with methylation of the leptin gene, LEP, in very young children. Leptin is one of the several neuropeptides involve in the regulation of food intake and fat metabolism. When a baby is breastfed, there is less methylation or silencing of the leptin gene, meaning that more leptin is produced. The decrease in LEP methylation could be one of the mechanisms by which breastfeeding contributes to protection against childhood obesity.16

Although more research is needed, obesity risk, which is clearly linked to nutrition and early-life diet, could be epigenetically stifled in children who are breastfed.

4. Cancer

Benefits of breastfeeding are not only limited to the breastfed child. Mothers can have a deep and relevant impact on their own health just by nursing their babies.

breastfeeding reduces chance of cancer
Further studies are needed to determine if breastfeeding might reduce a woman’s risk of breast cancer.

It is not very clear yet, but the evidence so far has shown an inverse correlation between breastfeeding duration and breast cancer risk, even in women who carry deleterious mutations in the BRCA1 gene.

This has been demonstrated by several studies, where women with BRCA1 mutations who breastfed their kids for more than one year showed a statistically significantly reduced risk of breast cancer than those who did not breastfeed their children. However, no association was found between breast cancer risk and breastfeeding for women with BRCA2 mutations. 15,17

Scientists have proposed several mechanisms that might explain this positive effect of nursing in breast-cancer risk reduction, such as hormonal changes. Another proposed mechanism is the inhibiting effect that DHA, a natural ligand of peroxisome proliferator-activated receptors, exerts on breast cancer cell growth and mammary tumor growth by epigenetically modulating PPAR βmRNA expression.15

Despite the potential role of breastfeeding and breast cancer prevention via epigenetic mechanisms, further studies are needed to clarify exactly how, or which specific components of human milk are involved.

Future Directions

It is clear that breast milk may not only improve neonatal nutritional status but could also optimize the health of future generations. It’s important for women to be educated on the numerous benefits of breastfeeding. Additional epigenetic studies will continue to uncover the potential underlying biological mechanisms which may help explain how breastmilk could epigenetically protect a child from developing diseases as he or she grows older.

It is also important to note that breastfeeding can be considered a cheap, accessible, and efficient tool to impact public health. We are hopeful that in the near future we may see more evidence supporting the power of breastfeeding.

Learn more about World Breastfeeding Week, held from August 1st-7th.

 

 

Show 16 footnotes

  1. Verduci, E., Banderali, G., Barberi, S., Radaelli, G., Lops, A., Betti, F., … Giovannini, M. (2014). Epigenetic Effects of Human Breast Milk. Nutrients, 6(4), 1711–1724. http://doi.org/10.3390/nu6041711.
  2. Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics.2012 Mar;129(3):e827-41. doi: 10.1542/peds.2011-3552.
  3. Apps.who.int. (2018). Online. Available at:
    http://apps.who.int/iris/bitstream/handle/10665/79198/9789241505307_eng.pdf;jsessionid=F372F102B1B61447756208F2D2F54864?sequence=1 (Accessed 27 Jul. 2018).
  4. Baumgartel, K. L., & Conley, Y. P. (2013). The Utility of Breastmilk for Genetic or Genomic Studies: A Systematic Review. Breastfeeding Medicine, 8(3), 249–256. http://doi.org/10.1089/bfm.2012.0054.
  5. Gicquel C, El-Osta A, Le Bouc Y. epigenéticos regulation and fetal programming. Best Pract Res Clin Endocrinol Metabo. 2008 Feb; 22 (1): 1-16. doi:10.1016 / j.beem.2007.07.009..
  6. Hartwig FP, Loret de Mola C, Davies NM, Victora CG, Relton CL. Breastfeeding effects on DNA methylation in the offspring: A systematic literature review. PLoSOne. 2017 Mar 3;12(3):e0173070. doi: 10.1371/journal.pone.0173070. eCollection2017. Review. Erratum in: PLoS One. 2017 Apr 6;12 (4):e0175604.
  7. Claud, E. C. (2009). Neonatal Necrotizing Enterocolitis –Inflammation and Intestinal Immaturity. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 8(3), 248–259. http://doi.org/10.2174/187152309789152020.
  8. Gao, F., Zhang, J., Jiang, P., Gong, D., Wang, J.-W., Xia, Y., … Sangild, P. T. (2014). Marked methylation changes in intestinal genes during the perinatal period of preterm neonates. BMC Genomics, 15(1), 716. http://doi.org/10.1186/1471-2164-15-716.
  9. Dąbek J, Kułach A, Gąsior Z. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB): a new potential therapeutic target in atherosclerosis? Pharmacol Rep. 2010 Sep-Oct;62(5):778-83. Review.
  10. Melnik, B. C., & Schmitz, G. (2017). Milk’s Role as an Epigenetic Regulator in Health and Disease. Diseases, 5(1), 12. http://doi.org/10.3390/diseases5010012.
  11. Verduci, E., Banderali, G., Barberi, S., Radaelli, G., Lops, A., Betti, F., … Giovannini, M. (2014). Epigenetic Effects of Human Breast Milk. Nutrients, 6(4), 1711–1724. http://doi.org/10.3390/nu6041711.
  12. Indrio, F., Martini, S., Francavilla, R., Corvaglia, L., Cristofori, F., Mastrolia, S. A., … Loverro, G. (2017). Epigenetic Matters: The Link between Early Nutrition, Microbiome, and Long-term Health Development. Frontiers in Pediatrics, 5, 178. http://doi.org/10.3389/fped.2017.00178.
  13. Yang Z, Huffman SL. Nutrition in pregnancy and early childhood and associations with obesity in developing countries. Matern Child Nutr. 2013 Jan;9 Suppl 1:105-19. doi: 10.1111/mcn.12010.
  14. Haemer, M. A., Huang, T. T., & Daniels, S. R. (2009). The Effect of Neurohormonal Factors, Epigenetic Factors, and Gut Microbiota on Risk of Obesity. Preventing Chronic Disease, 6(3), A96.
  15. Kotsopoulos, J., Lubinski, J., Salmena, L., Lynch, H. T., Kim-Sing, C., Foulkes, W. D., … Narod, S. A. (2012). Breastfeeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Research : BCR, 14(2), R42. http://doi.org/10.1186/bcr3138.
  16. Jernström H, Lubinski J, Lynch HT, Ghadirian P, Neuhausen S, Isaacs C, Weber BL, Horsman D, Rosen B, Foulkes WD, Friedman E, Gershoni-Baruch R, Ainsworth P, Daly M, Garber J, Olsson H, Sun P, Narod SA. Breast-feeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2004 Jul 21;96(14):1094-8.

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About Janeth Santiago Rios 4 Articles
Janeth Santiago Rios is a dietitian-nutritionist from Colombia with an MSc in Nutrition and Metabolism from Barcelona and Rovira i Virgili University. Janeth is passionate about healthy eating, writing, and helping others improve their quality of life through nutrition.

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