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.

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. 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. 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. 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. 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. D u P o n t N u t r i t i o n & H e a l t h
Human Milk Oligosaccharides
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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. 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
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Industry’s Partnership through Innovation

8. Thank You
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