When an infant is born, its immune system is not yet fully developed. Both the innate and adaptive immune systems need more time to be fully functional. For a long time, researchers believed that the innate immune system acts only as an immediate defence against invading pathogens, like bacteria and viruses, with limited specificity and little memory of how to respond to them. The adaptive immune system may react more slowly, but offers the benefit of a more specific response, as well as the ability to form immune memory. However, science has recently identified a new element of the innate immune system, known as “trained immunity,” or “innate immune training.”
It was found that the innate immune response towards a first infection can lead to development of innate immune memory, which is independent of the memory of the adaptive immune system. Just like adaptive immune response trained immunity leads to an elevated immune response in case of second infection
Netea, M. G., Quintin, J. & Van der Meer, J. W. M. Trained Immunity: A Memory for Innate Host Defense. Cell Host & Microbe 9 355-361 (2011).
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Some pathogens and pathogen-derived components, like those in vaccines, can induce trained immunity. Recently, there are indications from in vitro studies that dietary components also have the ability to induce trained immunity.
Van Splunter, M., Van Osch, T. L. J., Brugman, S. & Savelkoul, H. F. J. Induction of trained innate immunity in human monocytes by bovine milk and milk-derived immunoglobulin G. Nutrients 10 1378 (2018).
Pan, W., Hao, S., Zheng, M. & Lin, D. Oat-derived β-glucans induced trained immunity through metabolic reprogramming. Inflammation 43 1323-1336 (2020).
Bekkering, S., Quintin, J., Joosten, L. A. B. & Van der Meer, J. W. M. Oxidized low-density lipoprotein induces long-term proinflammatory cytokine production and foam cell formation via epigenetic reprogramming of monocytes, Arterioscler Thromb Vasc Biol 34 1731-1738 (2014).
Bekkering, S., Blok, B. A., Joosten, L. A. B. & Riksen, N. P. In vitro experimental model of trained innate immunity in human primary monocytes. Clin Vaccine Immunol 23 926-933 (2016).
Christ, A., Günther, P., Lauterbach, M. A. R. & Duewell, P. Western diet triggers NLRP3-dependent innate immune reprogramming. Cell 172 162-175 (2018).
Trained immunity plays an important role in the early years, as well as later in life when dealing with pathogens.
Breast milk contains a wide range of bioactive components that help to protect the infant against all kinds of infections.
Field, C. The immunological components of human milk and their effect on immune development in infants. J Nutr 135 1-4 (2005).
Most infant formulas on the market are based on bovine milk, which contains many immune-related components similar to those found in breast milk, although the concentrations are different and processing, especially heating, might impact their functionality.
Van Neervan, R. J. J., Knol, E. F., Heck J. M. L. & Savelkoul, H. F. J. Which factors in raw cow’s milk contribute to protection against allergies? J Allergy Clin Immunol 130 853-838 (2012).
Brick, T., Ege, M., Boeren, S. & Böck, A. Effect of processing intensity on immunologically active bovine milk serum proteins. Nutrients 9(9) 963 (2017).
Loss, G., Apprich, S., Waser, M. & Kneifel, W. The protective effect of farm milk consumption on childhood asthma and atopy: the GABRIELA study. J Allergy Clin Immunol 128(4) 766-773 (2011).
Hellinga et al. investigated whether two minimally-processed dairy streams from FrieslandCampina were able to induce trained immunity in human monocytes (blood cells) in vitro. Both whey protein concentrate Vivinal® MFGM and serum protein concentrate (SPC) were both demonstrated to achieve this. Both streams contain relatively high amounts of immunoglobulin G (bIgG). To study the contribution of bIgG to trained immunity induction, the team tested purified bIgG as well as two whey streams that had been depleted of bIgG. The results confirmed that bIgG can induce trained immunity in vitro, and also demonstrated that Vivinal® MFGM and SPC have the same ability, even when blgG is removed from these whey fractions.
As a result of this study, we can see strong evidence that minimally-processed dairy streams like Vivinal® MFGM and SPC may contribute to protection against infections, and they do so by enhancing the innate immune response towards pathogens.
Hellinga, A. H., Tsallis, T., Eshuis, T. & Triantis, V. et al. In vitro induction of trained innate immunity by bIgG and whey protein extracts. Int J Mol Sci 21 9077 (2020).
This is an exciting development for formulators seeking differentiated and value-adding ingredients for early life nutrition.
Vivinal® MFGM supports the development of the immune system via its potential role in gut maturation
Anderson RC, MacGibbon AKH, Haggarty N, et al (2018) Bovine dairy complex lipids improve in vitro measures of small intestinal epithelial barrier integrity. PLoS One. 2018 Jan 5;13(1):e0190839.
Motouri M, Matsuyama H, Yamamura J, et al (2003) Milk sphingomyelin accelerates enzymatic and morphological maturation of the intestine in artificially reared rats. J Pediatr Gastroenterol Nutr. 2003 Feb;36(2):241-7
Lee H, Zavaleta N, Chen S-Y, et al (2018) Effect of bovine milk fat globule membranes as a complementary food on the serum metabolome and immune markers of 6-11-month-old Peruvian infants. npj Sci Food 2:6.
Snow DR, Ward RE, Olsen a, et al (2011) Membrane-rich milk fat diet provides protection against gastrointestinal leakiness in mice treated with lipopolysaccharide. J Dairy Sci 94:2201–2212.
Bhinder G, Allaire JM, Garcia C, et al (2017) Milk Fat Globule Membrane Supplementation in Formula Modulates the Neonatal Gut Microbiome and Normalizes Intestinal Development. Sci Rep 7:45274.
, gut barrier function and by reducing the risk of infections.
Zavaleta, N. et al. Efficacy of an MFGM-enriched complementary food in diarrhea, anemia, and micronutrient status in infants. J. Pediatr. Gastroenterol. Nutr. 53, 561–568 (2011).
Timby, N. et al. Infections in infants fed formula supplemented with bovine milk fat globule membranes. J. Pediatr. Gastroenterol. Nutr. 60, 384–389 (2015).
Li F, Wu SS, Berseth CL, et al (2019) Improved Neurodevelopmental Outcomes Associated with Bovine Milk Fat Globule Membrane and Lactoferrin in Infant Formula: A Randomized, Controlled Trial. J Pediatr 215:24-31.e8.
Veereman-Wauters, G. et al. Milk fat globule membrane (INPULSE) enriched formula milk decreases febrile episodes and may improve behavioral regulation in young children. Nutrition 28, 749–752 (2012).
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