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D u P o n t N u t r i t i o n & H e a l t h
January 3, 2019
Angela Lim
Senior Manager, Regulatory Affairs
Global Regulator...
D u P o n t N u t r i t i o n & H e a l t h
Human Milk Oligosaccharides
• Soluble carbohydrates unique to human breast mil...
D u P o n t N u t r i t i o n & H e a l t h
Human Milk Oligosaccharides
3
• Current evidence suggests establishment of
Bif...
D u P o n t N u t r i t i o n & H e a l t h
No oligosaccharides
Decoy oligosaccharide
binds to pathogen
Human Milk Oligosa...
D u P o n t N u t r i t i o n & H e a l t h
Human Milk Oligosaccharides
Modulate immune response
5January 3, 2019
Similar ...
D u P o n t N u t r i t i o n & H e a l t h
Human Milk Oligosaccharides
6
The types and levels of HMOs vary considerably
a...
D u P o n t N u t r i t i o n & H e a l t h
Industry’s Partnership through Innovation
DuPont’s Contribution
• HMO product ...
Thank You
©2019 DowDuPont, The Dow Chemical Company, DuPont. All rights reserved.
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Human Milk Oligosaccharides (HMO) - Immune Health of Infants

Current evidence suggests that Human Milk Oligosaccharides (HMO) plays a role in promoting immune health in infants through changes to the microbiome. Angela Lim, senior manager, global regulatory affairs lead, HMO shares on the science behind it, and the opportunities and challenges that lie ahead.

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Human Milk Oligosaccharides (HMO) - Immune Health of Infants

  1. 1. D u P o n t N u t r i t i o n & H e a l t h January 3, 2019 Angela Lim Senior Manager, Regulatory Affairs Global Regulatory Affairs Lead, HMO Immune Health of Infants Human Milk Oligosaccharides
  2. 2. D u P o n t N u t r i t i o n & H e a l t h Human Milk Oligosaccharides • Soluble carbohydrates unique to human breast milk, made up of a lactose core bonded to other simple sugars 2 Human milk composition Macro- and Micronutrients HMOs in Human milk Water Nutrients Lactose Lipids Proteins HMOs Other HMOs 3FL 2’FL LnT 6’SL LNnT 3’SL DiFL • Mother’s genetic make up appears to influence type and quantity of HMOs secreted • 2’ Fucosyllactose (2’FL) most abundant • Average levels 2.4 g/L, high early in lactation stage, decreases later • Among the most studied HMOs to date • Third most abundant component after lactose & lipids; contributes to approximately 10% of total solids • Over 200 different oligosaccharides have been identified • Amount and composition of HMOs are highly variable among women • Each structurally defined HMO may have a distinct functionality
  3. 3. D u P o n t N u t r i t i o n & H e a l t h Human Milk Oligosaccharides 3 • Current evidence suggests establishment of Bifidobacteria early in life plays a role in programming future health • Findings from the last 10 years -- Bifidobacteria exert their beneficial effects on host health through the immunomodulatory action of some of their surface- associated molecules • Bifidobacteria are thought to exert their immunomodulatory activity mainly in the colon and in the distal part of the ileum, where up to 46% of the Peyer’s patches are located • More than 90% reaches an infant’s large intestine undigested • Provide nutrients for beneficial bacteria — particularly Bifidobacteria • 2’-FL, when added to infant formula, can help establish beneficial bacteria linked with immunity, such as Bifidobacteria Influence microbiota composition and/or activity Ruiz, L. et al (2017) Bifidobacteria and Their Molecular Communication with the Immune System
  4. 4. D u P o n t N u t r i t i o n & H e a l t h No oligosaccharides Decoy oligosaccharide binds to pathogen Human Milk Oligosaccharides 4 Adhesion (%) E. coli 11412 Control E. coli 11442 Control E. coli 42878 Control GOS 2’-FL Co-incubation with EC 42878 Co-incubation with EC 11442 GOS 2’-FL Co-incubation with EC 11412 GOS 2’-FL The effect of 2’-FL and GOS on adherence of E. coli 11412, -11442 and -42878 strains were studied in Caco-2 cells using Syto24 bacteria labelling and fluorometric detection • The adhesion of pathogens to human epithelial cells is usually the first step towards successful colonization and subsequent systemic infection • HMOs mimic cell surface receptor structures → Act as soluble decoys, preventing adhesion colonization of epithelial surfaces (Morrow et al, 2004; Coppa et al, 2006; Weichert et al, 2013) • 2’-FL decreases the adhesion of three E. coli strains of infant diarrhea origin on Caco-2 intestinal epithelial cells (DuPont study) Inhibit pathogen adhesion to intestinal mucosa
  5. 5. D u P o n t N u t r i t i o n & H e a l t h Human Milk Oligosaccharides Modulate immune response 5January 3, 2019 Similar to Those Who Are Breastfed, Infants Fed a Formula Containing 2′-Fucosyllactose Have Lower Inflammatory Cytokines in a Randomized Controlled Trial Goehring, K. et al (2016) Investigated the effects of feeding formulas supplemented with the 2’-FL HMO on biomarkers of immune function in healthy term infants • Randomized, double-blind, controlled growth and tolerance study in healthy term infants • Enrolled by day 5 of life, exclusively formula-fed (n = 317) or breast-fed (n = 107) from enrollment to 4 months of age Results: • Plasma inflammatory cytokines* concentrations No difference in breast-fed infants and infants fed 2’FL enriched formulas vs 29–83% in Infants fed the control formula (P ≤ 0.05) * Interleukin (IL) receptor antagonist (IL-1ra), IL-1α, IL- 1β, IL-6, and tumor necrosis factor α (TNF-α) • Ex-vivo RSV–stimulated PBMC cultures No difference in breast-fed infants and infants fed 2’FL vs Infants fed the control formula Conclusion: Supplementation of infant formula with a single HMO (2’FL) modified innate and adaptive immune profiles of formula-fed infants to be more like that of the breast- fed reference group. These findings indicate that 2’FL fortification supports aspects of immune development and regulation similar to that in a breast-fed reference group of infants.
  6. 6. D u P o n t N u t r i t i o n & H e a l t h Human Milk Oligosaccharides 6 The types and levels of HMOs vary considerably among women, regions, and the stages of lactation Frontier opportunities & challenges → intervention opportunity → beneficial to Infant health Need for more randomized, double-blinded, multicenter, controlled trials. Only a few infant studies on effects of HMOs on infection and immune function. Most of these studies are observational studies on breastfeeding infants, correlating HMOs in breastmilk with these outcomes. None of these studies have formally demonstrated direct effects of HMOs, and that other breastfeeding components may be associated with the effects described. Plaza-Diaz et al, 2018; Triantes et al, 2018
  7. 7. D u P o n t N u t r i t i o n & H e a l t h Industry’s Partnership through Innovation DuPont’s Contribution • HMO product family (CARE4U™ Brand) • 2’ Fucosyllactose • Others under development • Safety studies • 2’FL, 3FL • Clinical studies • 2’FL, 3FL • HMOs + Probiotics • Analytical methods • Detection in food matrix 7 Industry’s Partnership through Innovation
  8. 8. Thank You ©2019 DowDuPont, The Dow Chemical Company, DuPont. All rights reserved. ®™ Trademark of DowDuPont, The Dow Chemical Company, E.I. du Pont de Nemours and Company, or their affiliates. DuPont Nutrition & Health, a DowDuPont Specialty Products Division business, combines in-depth knowledge of food and nutrition with current research and expert science to deliver unmatched value to the food, beverage, pharmaceutical and dietary supplement industries. We are innovative solvers, drawing on deep consumer insights and a broad product portfolio to help our customers turn challenges into high-value business opportunities. More information is available at www.food.dupont.com.

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