Immunity is critical throughout life, but especially in the early years, when the immune system needs to be built up for long and healthy living. Immune health is a top priority for parents of babies and children, and nutrition plays an important role in supporting it. Learn how ingredient solutions from FrieslandCampina Ingredients can help your infant milk formula to support immune health in early life.
When a baby is born, its immune system is not yet mature. During the final stage of pregnancy, the baby does receive some protective immunoglobulins (IgG) from the mother. But unless the baby is breastfed, protective components decrease within a few months following birth
Niewiesk, S. Maternal antibodies: Clinical significance, mechanism of interference with immune responses, and possible vaccination strategies. Front. Immunol. 5, 1–15 (2014).
. It is essential that the newborn’s immune system develops and grows strong in order to reduce the risk of pathogenic infections. Infant immunity, which is primarily influenced by the gut
Vighi, G., Marcucci, F., Sensi, L., Di Cara, G. & Frati, F. Allergy and the gastrointestinal system. Clin. Exp. Immunol. 153, 3–6 (2008)
, can be supported in several different ways: by strengthening the gut barrier, inhibiting pathogen binding, modulating the immune response or by stimulating the growth of beneficial bacteria
Gewirtz, A. T. & Madara, J. L. (2001). Periscope, up! Monitoring microbes in the intestine. Nat. Immunol. 2001;2,288-290.
. Our ingredient solutions can support immunity during the most vulnerable period in early life.
Galacto-oligosaccharides (GOS) and the human milk oligosaccharides (HMOs*) 2’-Fucosyllactose (2’-FL), Lacto-N-tetraose (LNT) and 3-Fucosyllactose (3-FL) have been shown to stimulate the growth of Bifidobacteria in the infant gut by serving as a substrate
Watson D, O’Connell Motherway M, Schoterman MHC, van Neerven RJJ, Nauta A, Van Sinderen D. Selective carbohydrate utilization by lactobacilli and bifidobacteria. J Appl Microbiol. Published online 2013. doi:10.1111/jam.12105
Salli K, Hirvonen J, Siitonen J, Ahonen I, Anglenius H, Maukonen J. Selective Utilization of the Human Milk Oligosaccharides 2′-Fucosyllactose, 3-Fucosyllactose, and Difucosyllactose by Various Probiotic and Pathogenic Bacteria. J Agric Food Chem. Published online 2021. doi:10.1021/acs.jafc.0c06041
Asakuma S, Hatakeyama E, Urashima T, et al. Physiology of consumption of human milk oligosaccharides by infant gut-associated ifidobacterial. J Biol Chem. Published online 2011. Doi:10.1074/jbc.M111.248138
. Upon fermentation of oligosaccharides, Bifidobacteria produce metabolites such as short-chain fatty acids (SCFAs), which lower the gut pH, thereby promoting the further growth of beneficial bacteria
Ben, X.-M., Li, J., Feng, Z.-T., Shi, Z.-Y., Lu, Y.-D., Chen, R., & Zhou, X.-Y. (2008). Low level of galacto-oligosaccharide in infant formula stimulates growth of intestinal Bifidobacteria and Lactobacilli. World Journal of Gastroenterology, 14(42), 6564. https://doi.org/10.3748/wjg.14.6564
. Such environmental conditions in the gut also help to crowd out potentially pathogenic bacteria through competitive advantage
Salli K, Hirvonen J, Siitonen J, Ahonen I, Anglenius H, Maukonen J. Selective Utilization of the Human Milk Oligosaccharides 2′-Fucosyllactose, 3-Fucosyllactose, and Difucosyllactose by Various Probiotic and Pathogenic Bacteria. J Agric Food Chem. Published online 2021. doi:10.1021/acs.jafc.0c06041
Asakuma S, Hatakeyama E, Urashima T, et al. Physiology of consumption of human milk oligosaccharides by infant gut-associated ifidobacterial. J Biol Chem. Published online 2011. Doi:10.1074/jbc.M111.248138
Berger B, Porta N, Foata F, et al. Linking human milk oligosaccharides, infant fecal community types, and later risk to require antibiotics. Mbio. Published online 2020. Doi:10.1128/mBio.03196-19
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These underlying mechanisms of action have been connected with specific infant health outcomes: studies of babies nourished with formula containing GOS found a reduced incidence of infections
Ranucci G, Buccigrossi V, Borgia E, et al. Galacto-oligosaccharide/polidextrose enriched formula protects against respiratory infections in infants at high risk of atopy: A randomized clinical trial. Nutrients. Published online 2018. doi:10.3390/nu10030286
Arslanoglu S, Moro GE, Boehm G. Early supplementation of prebiotic oligosaccharides protects formula-fed infants against infections during the first 6 months of life. J Nutr. Published online 2007. doi:10.1093/jn/137.11.2420
. And in a study on formula containing 2’-FL and LNnT (Lacto-N-neotetraose), an association was found between gut microbiota communities high in Bifidobacteriaceae and a decreased risk of requiring antibiotics
Salli K, Hirvonen J, Siitonen J, Ahonen I, Anglenius H, Maukonen J. Selective Utilization of the Human Milk Oligosaccharides 2′-Fucosyllactose, 3-Fucosyllactose, and Difucosyllactose by Various Probiotic and Pathogenic Bacteria. J Agric Food Chem. Published online 2021. doi:10.1021/acs.jafc.0c06041
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Microbiota-independent immune-supporting effects have also been reported for ingredients like lactoferrin, milk fat globule membrane (MFGM), 2’-FL and polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and arachidonic acid (ARA).
Lactoferrin, a natural iron-binding milk glycoprotein, has been found to help the development and maturation of the gut during early life
Manzoni, P., Dall’Agnola, A., Tomé, D., Kaufman, D. A., Tavella, E., Pieretto, M., Messina, A., De Luca, D., Bellaiche, M., Mosca, A., Piloquet, H., Simeoni, U., Picaud, J. C., & Del Vecchio, A. (2018). Role of Lactoferrin in Neonates and Infants: An Update. American Journal of Perinatology, 35(6), 561–565. https://doi.org/10.1055/s-0038-1639359.
. It has been shown to reduce the risk of gut- and respiratory tract infections
Li, F., Wu, S. S., Berseth, C. L., Harris, C. L., Richards, J. D., Wampler, J. L., Zhuang, W., Cleghorn, G., Rudolph, C. D., Liu, B., Shaddy, D. J., & Colombo, J. (2019). Improved Neurodevelopmental Outcomes Associated with Bovine Milk Fat Globule Membrane and Lactoferrin in Infant Formula: A Randomized, Controlled Trial. Journal of Pediatrics. https://doi.org/10.1016/j.jpeds.2019.08.030
Zavaleta, N., Kvistgaard, A. S., Graverholt, G., Respicio, G., Guija, H., Valencia, N., & Lönnerdal, B. (2011). Efficacy of a Complementary Food Enriched with a Milk Fat Globule Membrane Protein Fraction on Diarrhea, Anemia and Micronutrient Status in Infants. Journal of Pediatric Gastroenterology and Nutrition. https://doi.org/10.1097/MPG.0b013e318225cdaf
Timby, N., Hernell, O., Vaarala, O., Melin, M., Lönnerdal, B., & Domellöf, M. (2015). Infections in infants fed formula supplemented with bovine milk fat globule membranes. Journal of Pediatric Gastroenterology and Nutrition. https://doi.org/10.1097/MPG.0000000000000624
presumably via multiple mechanisms of action: by binding iron, which is essential for viability of several pathogens; by directly inactivating pathogens; by blocking receptors for pathogens on epithelial cells; and by immuno-modulatory effects via direct interactions with gut epithelial cells and immune cells
Kell, D. B., Heyden, E. L., & Pretorius, E. (2020). The Biology of Lactoferrin, an Iron-Binding Protein That Can Help Defend Against Viruses and Bacteria. Frontiers in Immunology, 11, 1221. https://doi.org/10.3390/molecules20069703 .
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Consisting of phospholipids, cholesterol and glycoproteins, the tri-layered membrane surrounding milk fat droplets in human and bovine milk is known as the MFGM. Whey-based MFGM ingredients have been shown to support immune function: a reduced prevalence of diarrhoea
Zavaleta, N., Kvistgaard, A. S., Graverholt, G., Respicio, G., Guija, H., Valencia, N., & Lönnerdal, B. (2011). Efficacy of a Complementary Food Enriched with a Milk Fat Globule Membrane Protein Fraction on Diarrhea, Anemia and Micronutrient Status in Infants. Journal of Pediatric Gastroenterology and Nutrition. https://doi.org/10.1097/MPG.0b013e318225cdaf
and reduced episodes of middle ear infection
Timby, N., Hernell, O., Vaarala, O., Melin, M., Lönnerdal, B., & Domellöf, M. (2015). Infections in infants fed formula supplemented with bovine milk fat globule membranes. Journal of Pediatric Gastroenterology and Nutrition. https://doi.org/10.1097/MPG.0000000000000624
were observed in clinical trials studying infants. As a combination, lactoferrin and MFGM supplementation resulted in a lower incidence of upper respiratory tract infections and diarrhoea
Li, F., Wu, S. S., Berseth, C. L., Harris, C. L., Richards, J. D., Wampler, J. L., Zhuang, W., Cleghorn, G., Rudolph, C. D., Liu, B., Shaddy, D. J., & Colombo, J. (2019). Improved Neurodevelopmental Outcomes Associated with Bovine Milk Fat Globule Membrane and Lactoferrin in Infant Formula: A Randomized, Controlled Trial. Journal of Pediatrics. https://doi.org/10.1016/j.jpeds.2019.08.030
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A good immune response against pathogens that adhere to, and pass through the intestinal barrier and cause infections, is of key interest for infant immune health. 2’-FL can serve as a decoy receptor
Bode, L. (2012). Human milk oligosaccharides: Every baby needs a sugar mama. In Glycobiology. https://doi.org/10.1093/glycob/cws074 and inhibits in vitro binding of viral and bacterial pathogens associated with childhood diarrhoea, like norovirus, rotavirus and ETEC
and inhibits in vitro binding of viral and bacterial pathogens associated with childhood diarrhoea, like norovirus, rotavirus and ETEC
Laucirica, D. R., Triantis, V., Schoemaker, R., Estes, M. K., & Ramani, S. (2017). Milk Oligosaccharides Inhibit Human Rotavirus Infectivity in MA104 Cells. Journal of Nutrition, 147(9), 1709–1714.
Weichert, S., Jennewein, S., Hüfner, E., Weiss, C., Borkowski, J., Putze, J., & Schroten, H. (2013). Bioengineered 2’-fucosyllactose and 3-fucosyllactose inhibit the adhesion of Pseudomonas aeruginosa and enteric pathogens to human intestinal and respiratory cell lines. Nutrition Research (New York, N.Y.), 33(10), 831–838. https://doi.org/10.1016/j.nutres.2013.07.009
Weichert, S., Koromyslova, A., Singh, B. K., Hansman, S., Jennewein, S., Schroten, H., & Hansman, G. S. (2016). Structural Basis for Norovirus Inhibition by Human Milk Oligosaccharides. Journal of Virology, 90(9), 4843–4848. https://doi.org/10.1128/JVI.03223-15
. In addition, GOS was shown to inhibit the adhesion of E. coli to human intestinal cells
Ambrogi, V., Bottacini, F., Sharry, J. Mac, Breen, J. Van, Keeffe, E. O., Walsh, D., Schoemaker, B., Cao, L., Kuipers, B., Hernandez-hernandez, O., Moreno, F. J., & Schoterman, M. (2021). Bifidobacterial β -Galactosidase-Mediated Production of Galacto-Oligosaccharides : Structural and Preliminary Functional Assessments. Frontiers in Microbiology, 12(750635), 1–19. https://doi.org/10.3389/fmicb.2021.750635
. These data suggest that GOS and 2’-FL have a direct inhibitory effect on pathogen infection, shedding light on the role of oligosaccharides in supporting immunity in early life.
The long-chain polyunsaturated fatty acids (LCPUFAs) DHA and ARA like those in our microencapsulated Vana-Sana™ range, can potentially help to modulate immune responses in infants
Richard, C., Lewis, E. D., & Field, C. J. (2016). Evidence for the essentiality of arachidonic and docosahexaenoic acid in the postnatal maternal and infant diet for the development of the infant’s immune system early in life. In Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. https://doi.org/10.1139/apnm-2015-0660
. Studies with infant milk formulas supplemented with a combination of DHA and ARA have shown a lower incidence of immunity-related issues or fewer doctor visits
Birch, E. E., Khoury, J. C., Berseth, C. L., Castañeda, Y. S., Couch, J. M., Bean, J., Tamer, R., Harris, C. L., Mitmesser, S. H., & Scalabrin, D. M. (2010). The Impact of Early Nutrition on Incidence of Allergic Manifestations and Common Respiratory Illnesses in Children. Journal of Pediatrics. https://doi.org/10.1016/j.jpeds.2010.01.002
Lapillonne, A., Pastor, N., Zhuang, W., & Scalabrin, D. M. F. (2014). Infants fed formula with added long chain polyunsaturated fatty acids have reduced incidence of respiratory illnesses and diarrhea during the first year of life. BMC Pediatrics. https://doi.org/10.1186/1471-2431-14-168
. Moreover, early supplementation with LCPUFAs has been demonstrated to influence the profile of immune cells and cytokines in formula-fed infants, more closely mirroring the profile of infants who were breastfed
Field, C. J., Van Aerde, J. E., Robinson, L. E., & Clandinin, M. T. (2008). Effect of providing a formula supplemented with long-chain polyunsaturated fatty acids on immunity in full-term neonates. British Journal of Nutrition. https://doi.org/10.1017/S0007114507791845 .
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Immune health matters most to today’s mums, dads and caregivers, as new research from FrieslandCampina Ingredients and Innova Market Insights demonstrates
Innova Market Insights & RFC, Early Life Nutrition survey, 2020
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Parents report immune-related symptoms more than any other type of health concern during the first year of life.
At least 59% of parents with children aged 0-1 years want to support their child’s immunity – it’s their number one priority.
After iron, prebiotics** are the second-most preferred ingredient category by parents who are looking for immune health benefits for their little ones.
FrieslandCampina Ingredients is proud to play a leading global role in the infant and young child milk formula ingredient industry, backed by over 75 years of experience in ingredients manufacturing and research in early life nutrition. Discover our ingredient solutions that can support infant immune health.
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* Not from human milk
** The scientific definition of a prebiotic is “A substrate that is selectively utilized by host microorganisms conferring a health benefit”. Gibson. G.R.et al, Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017 Aug;14(8):491-502. Whether the claim prebiotic can be used on consumer products depends on local legislation.
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