BLOG BY Dr Harriet Holme MA Hons Cantab MBBS MRCPCH(2009) PhD RNutr

Breast Milk And The Microbiome

While many women choose to breastfeed as their preference, we should all be able to make an informed decision about how to feed your baby, free from societal judgement or mum guilt, and that unbiased accurate information is sometimes incomplete.

What is the microbiome?

While some bacteria are harmful, many are key to our health. The microbiome is the term used to cover the trillions of bugs, mostly made up of bacteria, that live on our skin and in our gut.

Why is the microbiome important?

We know that these single cell organisms play a huge role in many aspects of our health as adults, ranging from reduced risk of type 2 diabetes, obesity, immune function and even response to chemotherapy1.

How are baby’s microbiomes formed?

When breastfeeding, the mother and baby although individuals, have an interactive relationship, that is called a dyad; this is highlighted by how the friendly microorganisms in breastmilk (milk microbiota) are formed. A healthy gut microbiome was first thought to be established by exposure through vaginal delivery and secondly through transfer of bacteria through breastmilk1,2 but there is now evidence that this is simplified, with many additional factors playing a role2.

Live microorganisms are already found in breastmilk, even before a mother has breastfed her baby for the first time, providing evidence of maternal origin (called entero-mammary pathway)2. The microorganisms in the baby’s mouth are similar to the mother’s breastmilk. New evidence suggests that in addition to maternal transfer, there is also communication via the baby’s saliva back into the breast, which also has a role in determining the microbiome2.

Mode of delivery, older siblings, maternal and infant antibiotic exposure, complementary feeding with formula milk, and even mode of feeding (pumped breastmilk versus directly at the breast) are all thought to play a part in determining the baby’s gut microbiome2. Some of these factors may only act in the short term, for example there is some evidence to suggest that mode of delivery has no persistent effect at 8 months3. While others may have a more long term effect, for example, stool microbiome profiles of children at 1 year were significantly different in those that were still breastfed, compared to those that weren’t4. This was independent of previous antibiotic exposure or mode of delivery4. More research is still needed to determine why the microbiome is different with pumped breastmilk compared with direct transfer, to answer whether it is the act of pumping or lack of contact with the baby’s mouth2.

Ultimately whether breastmilk provides the microorganisms to colonise the baby’s gut, or provides nutrients and prebiotics to foster a specific environment for selective growth of certain microorganisms, or a mixture of both, has yet to be fully established2. However, maturation and maintenance of the lining of the infant gut depends on bacterial colonisation5 and with evidence to support a long term health impact2,6,7

Why is breastmilk different?

Breastmilk contains a number of different components that make it different to formula milk, that are hard to replicate. In addition to the microorganisms, other components of breastmilk such as immune cells, fatty acids, antibodies, and human milk oligosaccharides (HMOs), also have a role in shaping the diversity of organisms2.

Human milk oligosaccharides

Human milk oligosaccharides (HMOs) are short chain carbohydrates, which are present in breastmilk that are essentially undigested by the baby, but are an important nutrient source for specific types of bacteria in the gut, called prebiotics8. One of the bacteria commonly seen the gut of healthy babies is Bifidobacterium longus infantis that metabolise HMOs into acetate and lactate9. These compounds are acidic, and change the pH of the infant stool, which are associated with lower levels of potentially harmful bacteria and those that harm the lining of the gut9. The formation of other bacteria that are potentially harmful, maybe prevented by HMOs, thereby shaping the formation of the microbiome, improving the barrier function of the lining of the gut, and playing a role in immune function8.

Lactoferrin

Lactoferrin, found in breastmilk, binds iron for transfer and aids it’s absorption through the infant gut lining8. This has a duel role, firstly helping the baby to absorb and use this iron as an important nutrient, and also leading to a reduction of the quantity of iron in the gut, which prevents harmful bacterial growth8.

Antibodies in Breastmilk

Antibodies are used to tag microbes like viruses and bacteria, for destruction by other immune cells. Levels of certain antibodies (IgA, IgG and IgM), have been found to be higher in the guts of babies who are breastfed10. When babies are born, they are initially unable to produce the antibodies they need.

Breastmilk functions to supply these antibodies for the first few weeks until the baby is able to produce enough themselves10. Supply of antibodies from breastmilk means that babies who are breastfed, have a lower risk of some childhood infections8.

Low levels of antibodies (specifically IgA), as a baby has been associated with increased risk of development of allergies and asthma during childhood11, and development of Crohn’s disease (chronic inflammatory condition of the gut), in children12.

Xanthine oxidase

Interestingly breastmilk contains an enzyme called xanthine oxidase, while neonatal saliva contains the substrates for this enzyme (xanthine and hypoxanthine). When the enzyme mixes with these substrates in the mouth and intestinal tract of the baby, a chemical reaction occurs, releasing hydrogen peroxide. This is antibacterial, and regulates the growth of some bacteria, possibly with a role in creating the different microbiome seen in breastfed babies13.

Does the type of milk matter?

Animal studies in monkeys have found that there are changes in the immune system in exclusively breastfed babies compared to those who are fed formula, and that these changes persist for 3-5 years after birth, long after weaning14.

In humans, gut bacteria have been found to differ between exclusively breastfed and formula fed babies5. Prebiotic like compounds added to formula milk, predict a microbiome distinct to that seen in an exclusively breastfed baby3. While mix fed babies have a microbiome that appears to be on a spectrum between that of breastfed and formula fed babies15.

What about weaning?

Introduction of complementary foods (weaning) changes the microbiome in the baby’s gut. Early weaning starting at 4 months or before, has been associated with a 30% higher risk of being overweight or obese (high Body Mass Index) in childhood, and a less diverse gut microbiome16. A high Body Mass Index (BMI) in childhood is associated with a higher future risk of high cholesterol profile, high blood pressure, diabetes and cardiovascular disease17.  However, those children who were breastfed for more than 4 months, did not have a higher BMI at 5 years, regardless of age at weaning16, so breastfeeding appears to be protective.

Are there benefits of breastmilk long term?

The first 1000 days of life is a critical period for development of the immune system4, and up to 70% is associated with the gut18. In the first few months of life, patterns are established for recognising self and non-self (highly important in autoimmune diseases), that have life-long consequences6,7.

There is evidence that the incidence of eczema, and wheezing in the first 2 years of life can be decreased by exclusive breastfeeding for 3 to 4 months19. Additionally, evidence suggests that a longer duration of breastfeeding may protect against asthma after the age of 5 years19. Breastfeeding has not been shown to prevent or delay the onset of specific food allergies19

Maternal benefits of breastfeeding

For mothers, in addition to the psychological aspect of bonding, breastfeeding decreases the risk of breast cancer and may protect against ovarian cancer and type 2 diabetes20.

This post was written by Dr Harriet Holme who studied medicine at the University of Cambridge and has over a decade of experience as a paediatric doctor. Harriet also has a PhD in genetics from University College London. Harriet now uses her skills for the benefit of her clients and students, exclusively consulting as a Registered Nutritionist with the Association of Nutrition and lecturing in culinary science and nutrition. You can find Harriet @healthyeatingdr and on her website Healthy Eating Dr.

References:

1. Lynch, S. V. & Pedersen, O. The Human Intestinal Microbiome in Health and Disease. https://doi.org/10.1056/NEJMra1600266 375, 2369–2379 (2016).

2.   Moossavi, S., Sepehri, S., Robertson, B., Bode, L., Goruk, S., Field, C. J., Lix, L. M., de Souza, R. J., Becker, A. B., Mandhane, P. J., Turvey, S. E., Subbarao, P., Moraes, T. J., Lefebvre, D. L., Sears, M. R., Khafipour, E. & Azad, M. B. Composition and Variation of the Human Milk Microbiota Are Influenced by Maternal and Early-Life Factors. Cell Host & Microbe 25, 324–335.e4 (2019).

3.   Baumann-Dudenhoeffer, A. M., D’Souza, A. W., Tarr, P. I., Warner, B. B. & Dantas, G. Infant diet and maternal gestational weight gain predict early metabolic maturation of gut microbiomes. Nat. Med. 24, 1822–1829 (2018).

4.   Matsuyama, M., Gomez-Arango, L. F., Fukuma, N. M., Morrison, M., Davies, P. S. W. & Hill, R. J. Breastfeeding: a key modulator of gut microbiota characteristics in late infancy. Journal of Developmental Origins of Health and Disease 10, 206–213 (2019).

5.   Solís, G., de Los Reyes-Gavilan, C. G., Fernández, N., Margolles, A. & Gueimonde, M. Establishment and development of lactic acid bacteria and bifidobacteria microbiota in breast-milk and the infant gut. Anaerobe 16, 307–310 (2010).

6.   Arrieta, M.-C., Stiemsma, L. T., Dimitriu, P. A., Thorson, L., Russell, S., Yurist-Doutsch, S., Kuzeljevic, B., Gold, M. J., Britton, H. M., Lefebvre, D. L., Subbarao, P., Mandhane, P., Becker, A., McNagny, K. M., Sears, M. R., Kollmann, T., Investigators, T. C. S., Mohn, W. W., Turvey, S. E. & Finlay, B. B. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Science Translational Medicine 7, 307ra152–307ra152 (2015).

7.   Insel, R. & Knip, M. Prospects for primary prevention of type 1 diabetes by restoring a disappearing microbe. Pediatric Diabetes 19, 1400–1406 (2018).

8.   Kleist, S. A. & Knoop, K. A. Understanding the Elements of Maternal Protection from Systemic Bacterial Infections during Early Life. Nutrients 12, 1045 (2020).

9.   Duar, R. M., Kyle, D. & Casaburi, G. Colonization Resistance in the Infant Gut: The Role of B. infantis in Reducing pH and Preventing Pathogen Growth. High-Throughput 2020, Vol. 9, Page 7 9, 7 (2020).

10. Janzon, A., Goodrich, J. K., Koren, O., TEDDY Study Group, Waters, J. L. & Ley, R. E. Interactions between the Gut Microbiome and Mucosal Immunoglobulins A, M, and G in the Developing Infant Gut. mSystems 4, 759 (2019).

11. Dzidic, M., Abrahamsson, T. R., Artacho, A., Björkstén, B., Collado, M. C., Mira, A. & Jenmalm, M. C. Aberrant IgA responses to the gut microbiota during infancy precede asthma and allergy development. J. Allergy Clin. Immunol. 139, 1017–1025.e14 (2017).

12. De Palma, G., Nadal, I., Medina, M., Donat, E., Ribes-Koninckx, C., Calabuig, M. & Sanz, Y. Intestinal dysbiosis and reduced immunoglobulin-coated bacteria associated with coeliac disease in children. BMC Microbiol. 10, 63–7 (2010).

13. Sweeney, E. L., Al-Shehri, S. S., Cowley, D. M., Liley, H. G., Bansal, N., Charles, B. G., Shaw, P. N., Duley, J. A. & Knox, C. L. The effect of breastmilk and saliva combinations on the in vitro growth of oral pathogenic and commensal microorganisms. Sci Rep 8, 1–9 (2018).

14. Narayan, N. R., Méndez-Lagares, G., Ardeshir, A., Lu, D., Van Rompay, K. K. A. & Hartigan-O'Connor, D. J. Persistent effects of early infant diet and associated microbiota on the juvenile immune system. Gut Microbes 6, 284–289 (2015).

15. Borewicz, K., Suarez-Diez, M., Hechler, C., Beijers, R., de Weerth, C., Arts, I., Penders, J., Thijs, C., Nauta, A., Lindner, C., Van Leusen, E., Vaughan, E. E. & Smidt, H. The effect of prebiotic fortified infant formulas on microbiota composition and dynamics in early life. Sci Rep 9, 1–13 (2019).

16. Differding, M. K., Doyon, M., Bouchard, L., Perron, P., Guérin, R., Asselin, C., Massé, E., Hivert, M.-F. & Mueller, N. T. Potential interaction between timing of infant complementary feeding and breastfeeding duration in determination of early childhood gut microbiota composition and BMI. Pediatr Obes 9, e12642 (2020).

17. Juonala, M., Magnussen, C. G., Berenson, G. S., Venn, A., Burns, T. L., Sabin, M. A., Srinivasan, S. R., Daniels, S. R., Davis, P. H., Chen, W., Sun, C., Cheung, M., Viikari, J. S. A., Dwyer, T. & Raitakari, O. T. Childhood adiposity, adult adiposity, and cardiovascular risk factors. N Engl J Med 365, 1876–1885 (2011).

18. Bäckhed, F., Roswall, J., Peng, Y., Feng, Q., Jia, H., Kovatcheva-Datchary, P., Li, Y., Xia, Y., Xie, H., Zhong, H., Khan, M. T., Zhang, J., Li, J., Xiao, L., Al-Aama, J., Zhang, D., Lee, Y. S., Kotowska, D., Colding, C., Tremaroli, V., Yin, Y., Bergman, S., Xu, X., Madsen, L., Kristiansen, K., Dahlgren, J. & Wang, J. Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. Cell Host & Microbe 17, 690–703 (2015).

19. Greer, F. R., Sicherer, S. H., Burks, A. W., COMMITTEE ON NUTRITIONSECTION ON ALLERGY AND IMMUNOLOGY. The Effects of Early Nutritional Interventions on the Development of Atopic Disease in Infants and Children: The Role of Maternal Dietary Restriction, Breastfeeding, Hydrolyzed Formulas, and Timing of Introduction of Allergenic Complementary Foods. Pediatrics 143, e20190281 (2019).

20. Victora, C. G., Bahl, R., Barros, A. J. D., França, G. V. A., Horton, S., Krasevec, J., Murch, S., Sankar, M. J., Walker, N., Rollins, N. C.Lancet Breastfeeding Series Group. Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet 387, 475–490 (2016).

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