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HMO: Supporting Infant Immunity and Beyond

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HMO: Supporting Infant Immunity and Beyond SPONSOR FEATURE HMO: Supporting Infant Immunity and Beyond AUTHOR Rachael H. Buck, PhD, Research Fellow, Abbott ADDRESS/CONTACT DETAILS 100 Abbott Park Road, Abbott Park, Illinois 60064 Rachael H. Buck, PhD, Director of Preclinical Research, Volwiler Research Fellow, and Gut Health Platform Leader, at Abbott or more than two decades, in the gut, which is colonized by general pathogen destruction. mechanism against invasion by Abbott has been researching trillions of microbes. Although Innate immunity not only is inhaled and ingested pathogens Fhuman milk oligosaccharides colonization begins during the the first line of defense, but also at vulnerable mucosal surfaces. (HMOs) to better understand birthing process, infants acquire induces acquired (or adaptive) Other immune components in how these prebiotics help support more than a thousand different immunity. After exposure to breast milk include: the infant immune system. A species before one year of age. specific pathogens and toxins, • leukocytes, which ingest or kill breakthrough occurred in 2010, The principal roles of the an infant’s acquired immune pathogens; when our team of scientists immune system during infancy pathway matures and produces • nucleotides, which support began to focus attention on the are to protect the host from antibodies targeted to specific adaptive immunity by specific HMO, 2’-fucosyllactose pathogens and eliminate toxic harmful invaders. In contrast to stimulating antibody (2’-FL). Since then, we have substances that enter through innate immune cells, adaptive production and lymphocyte published more than 20 preclinical mucosal surfaces lining the immune cells respond in weeks maturation; and and clinical studies on 2’-FL to respiratory and intestinal instead of hours or days, and • IgG antibodies, which describe its role in the developing tracts. Initially, maternal develop memories for removal of identify and bind to harmful infant immune system; its anti- immunoglobulin G (IgG) from the future threatening substances. substances such as bacteria, infective and prebiotic effects; placenta provides much of the Optimal early development viruses, and fungi to trigger an and its potential role in cognitive infant’s postnatal protection. This of both pathways is especially immune response. development. We were the first IgG declines rapidly after birth, critical because innate immune A growing body of evidence company in the world to add however, which makes the first cells do not reach adult levels now suggests that the HMOs an HMO to infant formula, and year of life an especially critical until approximately 12 months of found in breast milk play a critical we will continue to expand our time for infants to grow the age. Furthermore, major adaptive role in the development of healthy research with one overarching dense community of commensal immunity antibodies such as IgG immune systems. goal: to simulate the beneficial bacteria that is needed to and immunoglobulin M will only properties of breast milk in our establish and maintain a healthy reach 80 and 75 percent of adult HMOS AND 2’-FL: THE NEXT formula in order to narrow the immune system. levels, respectively, at one year FRONTIER OF PEDIATRIC gaps between breast-fed and All mammals, including of age. NUTRITION formula-fed infants – to give humans, have two pathways HMOs are the third most babies around the world the best for immune response—innate NUTRITION’S INTEGRAL abundant component in breast start in life. and acquired. Innate immunity ROLE IN IMMUNE milk (after fat and lactose, refers to nonspecific defense DEVELOPMENT a digestible carbohydrate), INNATE AND ADAPTIVE mechanisms such as natural killer The numerous protective comprising about 10 percent of IMMUNITY: THE CRUCIAL cells, a type of white blood cell, compounds in breast milk serve solids . Research suggests that FIRST YEAR that immediately attack foreign multiple functions within the HMOs serve as soluble decoy About 70% of the immune cells. During the first months of immune system. The most receptors that bind pathogens system’s many biological life, the infant relies largely on abundant antibody in human milk and prevent their attachment structures and processes reside its innate immune pathway for is secretory IgA, a key defensive to infant mucosal surfaces, thus Sponsor retains sole responsibility for content SPONSOR FEATURE lowering the risk for infection CLINICAL STUDY OF 2’-FL IN development and regulation that the effect of 2’-FL on CNS by these viruses or bacteria1. INFANT FORMULA similar to that in a breast-fed function was likely mediated HMOs are also thought to be A recent clinical trial compared reference group of infants. through the vagus nerve15. involved in modulating epithelial term infants fed an experimental and immune cell responses, infant formula containing 2’-FL INFANT NUTRITION AND THE A FOUNDATION FOR GOOD including the reduction of with breast-fed infants as well GUT-BRAIN-MICROBIOTA HEALTH excessive mucosal leukocyte as those in a control group AXIS Research shows us that infiltration and activation. who were fed formula without Nutrition plays an important role the development of the Of the more than 200 2’-FL8. The study found that the in supporting the rapidly growing immune system is closely HMO structures reported2, we 2’-FL-fortified formulas were brain during the first year of life. associated with the intestinal became particularly interested well-tolerated and that growth While some nutrients such as microbiota, highlighting in 2’-FL due to its unique was no different from that of docosahexaenoic acid, lutein, and the important connecting properties. Although 2’-FL is breast-fed infants. Interestingly, vitamin E appear to act directly in roles of HMOs as prebiotics quantitatively the most abundant reports of eczema were lower in the brain, new research indicates and immunomodulators. oligosaccharide in breast milk, the 2’-FL groups than the control that others influence the brain As awareness grows of the only 70-80% of women are group, and were no different from through the action of trillions of importance of early nutrition genetically capable of producing breast-fed infants. The study microbes that reside within the on life-long health, Abbott will it3. More importantly, however, also investigated the effects of gut. Some of these gut microbes continue to partner with experts recent research shows that feeding formulas supplemented generate metabolites that are worldwide in exploring the myriad 2’-FL might exert a variety of with 2’-FL on biomarkers of identical to the neurotransmitters of connections between infant beneficial physiological effects. immune function9. Following six found in the human brain, thus nutrition, gut microbiota, immune One study found that breast- weeks of feeding, researchers implying bidirectional host- development and brain health to fed infants whose mothers discovered that five immune microbe communication via a ensure we’re doing all we can to secreted 2’-FL could much more markers were significantly gut-brain-microbiota axis10. give babies around the world the readily establish gut populations lower in infants who were fed In addition to supporting the best start in life. of beneficial bifidobacteria the formulas containing 2’-FL developing immune system, than could breast-fed infants compared to control formula, both sialylated and fucosylated REFERENCES of non-secretor mothers4. In and they were nearly identical to HMOs are likely involved in 1. Bode L. Human milk oligosaccharides: another clinical study, the level those of breast-fed infants. The shaping the developing nervous every baby needs a sugar mama. of 2’-FL HMO in mother’s milk results showed that 2’-FL: system. Both sialylated11 and Glycobiology. 2012;22:1147-1162. was correlated to reduced risk of • reduced production of plasma fucosylated12 molecules have 2. Ninonuevo MR, Park Y, Hongfeng enteric infections in breast-fed pro-inflammatory cytokines been shown to participate in Y, et al. A strategy for annotating the infants5. to levels similar to breast-fed synaptic signaling. Furthermore, human milk glycome. J Agric Food Chem. 2006;54:7471-7480. Data from preclinical studies infants; sialylated HMOs may also serve 3. Castanys-Munoz E, Martin MJ, Prieto also hint at additional uses • closed plasma cytokine gaps as a source of sialic acid, a key PA. 2’-fucosyllactose: an abundant, for 2’-FL HMO. Experiments between breast-fed and nutrient for central nervous genetically determined soluble glycan using ex vivo murine colonic formula-fed infants; and system/brain development present in human milk. Nutr Rev. segments demonstrate that • narrowed respiratory and function13. Indeed, a study s2013;71(12):773-89. 6 2’-FL modulates gut motility , syncytial virus ex vivo cytokine in pigs found that sialylated 4. Lewis ZT, Totten SM, Smilowitz JT, suggesting that it might gaps between breast-fed and HMOs serve dual functions et al. Maternal fucosyltransferase 2 potentially be useful for reducing formula-fed infants. as: a source of sialic acid that status affects the gut bifidobacterial abdominal discomfort caused With respect to adaptive modulates brain composition, communities of breastfed infants, by colic or irritable bowel immunity, the study noted and a prebiotic to promote the Microbiome 2015;3:13. 14 syndrome, or for improving that 2’-FL also narrowed the growth of beneficial bacteria . 5. Morrow AL, et al. Human milk feeding tolerance in preterm differences in proportions of total Likewise,
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