Nutritional Systems Biology
Translated – Perspectives from an
Industry RD
23 October 2015
Colleen Fogarty Draper MS, RD
Nutritional Genomics Senior Specialist
PhD candidate, Leiden University
© 2015 Nestlé
NIHS in 2015
Location:
– Based at EPFL (École Polytechnique Fédérale de Lausanne)
Employees:
– 150
– 61% Ph.D., 19% Master
– 28 nationalities
– Average age: 39
Scientific development and interaction:
– 9 Adjunct MER/Professors
– PhD & Master program
– 100+ publications
– 4 grants
Established partnerships:
– Numerous collaborations with national and international
partners
© 2015 Nestlé
Photo by Alan Herzog
Scientific and Technology Platforms
• Cognitive Health
• Sarcopenia / Ageing of
Skeletal Muscles
• Personalised Nutrition & Health
-
Nutrition and Metabolic Health
Molecular Nutrition
• Obesity &
Weight mngt
• Diabetes
• Metabolic
sensing &
adaption
• Beta Cell
Function
• Circadian Cycle
• Cell Biology
-
Stem Cells
Flow Cytometry
Device Engineering
• Mitochondrial
Function
• Biosystems
Informatics
• Natural
Bioactives &
Screening
• GI Health and Microbiome
• Lipid Biology
• Functional Genomics
© 2015 Nestlé
• Molecular Biomarkers
Our Vision
Developing the scientific foundation of how
nutrition can empower people to improve and
maintain their health
© 2015 Nestlé
Business Areas Nestlé Health Science
 Healthy Ageing
 Other benefit areas
• Physical and cognitive autonomy: mobility, energy,
body+mind, cognitive capacity




Inborn Errors of Metabolism
Paediatric Care & Allergy
Acute Care (incl. critical ill; dysphagia, oncology)
Metabolic & Obesity Care
 Brain Health
 Gastrointestinal Health
© 2015 Nestlé
 US MN Specialties
 Devices
 Diagnostics
 Nutrient-based
technology platform
Company History
Key acquisitions, partnerships, investments
Acquisition
Diagnostics & Pharmaceuticals in GI Health &
Oncology
2011
Minority
Neurological
disorders (e.g.
Alzheimer’s)
2012
Joint Venture
Gastrointestinal
dis. TCM* library
2013
Acquisition
Metabolic & Neurologic conditions
2013
Acquisition
Inborn errors
of metabolism
2010
NHSc Corp. PPT, Feb. 2015
** TCM = Traditional Chinese Medicine
© 2015 Nestlé
Minority Investment
- Seres (microbiome)
Innovation Partnership
- Flagship
2014/15
Improved
Personal
Health
Nutritional
Systems
Biology
R&D
Nutrition in
Practice
Experience
ILI 2005
Women as Potential Personalized Nutrition Consumers
9
Women’s Health Workshop18 Sept 2015
US Data
10
Women’s Health Workshop18 Sept 2015
282/Nature/Vol
509/15
May 2014
11
Existing knowledge
Energy intake
Blood sugar
Insulin
Gastric emptying
emptying
GLP-1
Hunger
Endogenous lipid
synthesis
Cholesterol
CHO oxidation
Cravings and intake high fat, sugars
Blood Sugar
Homocysteine (possibly related to B6, B12, folate)
Insulin
Exacerbation of bowel symptoms in IBD
Bloating
HPA axis response to stress
Serotonin
Body temp
Sleep quality
Cortisol
Luteal Phase
Higher metabolic rate
Solomon et al Am J Clin Nutr 1982
Webb et al Am J Clin Nutr. 1986
Bisdee et al Brit J Nutr 1989
Larger appetite
Serotonin
cortisol
Stress response
sleep
Truchan et al Can J Physiol Pharma
1987
Li ET, et al
Appetite,1999.
Decrease in CHO oxidation
Baker et al Sleep Med,2007
Shechter A., et al.,SLEEP,2010
Hackney et al Int J Sport Nutr 1994.
Zderic et al
J Apl Physiol,2001
Poor blood sugar/insulin control
Campbell et al AmJPhysiolEndocrinolMetab
2001
Gugapriya et al Clin Diag Res,201
.
Higher protein needs ???
(nitrogen wasting, lower AA levels)
Wallace et al Hum Reprod Advance, 2010.
Calloway et al Am Inst Nut,1982.
Systematic view of metabotype variations in the metabolism of males and females
Mittelstrass K, Ried JS, Yu Z, Krumsiek J, Gieger C, et al. (2011) Discovery of Sexual Dimorphisms in Metabolic and Genetic Biomarkers. PLoS
Genet 7(8): e1002215. doi:10.1371/journal.pgen.1002215
http://127.0.0.1:8081/plosgenetics/article?id=info:doi/10.1371/journal.pgen.1002215
Menstrual cycle phase and metabolomic profiles in
premenopausal women
n=32
BMI 22.9 +/- 3.5
age 26.6 +/- 5/9
Page 15
Wallace M., etal. Hum Reprod Advance Access, February 10, 2010
Metabolomic Profiles
Menstrual Cycle Phase
The opportunity
Metabolite Menstrual Follicular
Luteal
Lysine 1
Lysine 2
Alanine
Glutamine 1
Glutamine 2
5.41
Creatinine
Glycine
Serine
2.59
VLDL CH2
30.47
Hydroxybuty
rate
6.4
Acetoacetate
14.6
Low
High
P-value
0.008
0.001
0.007
0.007
0.019
0.05
0.033
0.002
0.013
0.625
0.014
• Serum, plasma, urine samples available for
retrospective analyses.
• Characterization of cyclical nutrition and metabolic
health.
Throughout the cycle, we will characterize:
• Blood glucose metabolism
• Micronutrients
• Proteomic and metabolomics (LCMS,GCMS)
• Neurotransmitter response
• Stress response
• Use novel techniques in cyclical data analysis
Wallace M., etal. Hum Reprod
Advance Access, February 10, 2010
16
Luteal
Lutealand
andMenstrual
MenstrualDifferences
Differences(relative
(relativetotoFollicular)
Follicular)
17
Data adapted by C. Draper and D. deLorenzo from: Wallace M., etal. Hum Reprod Advance Access, February 10, 2010
Micronutrient Genomics
Baseline
2013 = 141
Design
Aggregated n-of-1 nutritional intervention design
98% compliance graduate students observed intake
2014 = 138
Replication in one study in 15 months
Intervention
5 days/wk
6 week
Validation in one study 69 participated in both
Comprehensive omics multi-scale integration
Post Intervention
Standard statistical & systems analysis
2013 = 139
2014 = 136
Assessments
Wash out
6 week
Post Washout
2013 = 136
2014 = 135
Food intake
SES
Anthropometric
Blood sampling
Impedance
Clinical
CBC
Physical Activity
Motion
Steps
Skin Temp
Heat
Galvanic
BMR
Metabolomics
Genomics
~200 metabolites:
Vitamins, lipids, amino acids
5 million SNPs & exome
& DNA damage analysis
Proteomics
GIS Mapping
< 1100 plasma proteins
DNA aptamer technologies
Food access& quality
Public health data
Jacqueline Monteiro, 8 graduate, &
25 undergraduate students
Courtesy of Jim Kaput
Menstrual disorders among adolescent girls are common due to immaturity of
hypothalamic-pituitary-ovarian (HPO) axis, however, exact incidence is
unknown….menstrual problems can be symptoms of conditions like POS, and
endometriosis, which if undiagnosed and untreated may have profound long-term sequelae
in adult life.
Abdelmoty H, et al. BMC
Women’s Health (2015) .
19
Medical Symptoms Questionnaire
www.IFM.org
What is the opportunity?
21
•
Characterization of menstrual cycle phase brings a new dimension to a product development
focus in women’s and adolescent health.
•
By characterizing early metabolic health through diagnosis, we create new opportunities to
build food and nutrition products.

Identification of cycles of micronutrient change translate to different nutrient/physiological
needs modifiable by diet and nutrition product strategies.
•
Characterization of differences in adolescent boys and girls will help us define differences in
health that translate to new optimal nutrition therapies for boys and girls.
•
Understanding biological system differences in association with symptoms can give us insight
on how to remedy nutrition imbalances and prevent menstrual disorders.
Need3toDay
build Diet
systems
that are:
Sample
Diary
•
•
•
• Electronic
• Easy to use
15 days/subject
• data
Accurate
Manual
entry • Reliable
PRODI
• Global
database for
• Comprehensive
analysis
Swiss Electronic FFQ
Development Q1 2014-Q3
2015
Food
Photography Lab
Page 23
Swiss FFQ Development Core Team
Colleen Draper
Clinical Nutritionist
NIHS FFQ PL
Esther Infanger
Muriel Jaquet
Swiss Nutritionist
Swiss Nutrition Society
Swiss-German
Swiss Nutritionist
Swiss Nutrition Society
Swiss-French
Jim Kaput
Pilar Giner
Head, Systems Nutrition
and Health Unit
& Photographer
Visiting scholar,
FoodP
Diena Seeger
COO
Viocare PM
Senior PM-R&D PM
Bio System
Informatics
Cris Milone
Swiss Dietitian/Nutritionist
Consultant NIHS
Swiss-Italian
Rick Weiss
President, CEO
Viocare
Automated generation of nutrient composition data
25
Conclusions
Personalized nutrition research and products can be
designed from different perspectives, such as
gender…
…Dietitians and clinicians play an
important role in the design of
translatable systems biology research …
…and high quality
electronic tools for
nutrition research are
essential!
© 2015 Nestlé
Backup
27
Food Photography Lab
29
31
Vegan Diet 2200 Kcal
Clinical Study Schema
Personalized Healthy Challenge
Kinetics+
OGFTT
Inclusion and
baseline
Kinetics+
OGFTT
OGFTT
OGFTT
CHO Challenges
OGFTT
Wt Loss Diet + Cyclic AM Protein Shake Intervention
Usual Diet + AM Pro Shake
Protein
Follow
up
CHO
Challenges
Protein
Protein
Protein
* Menstrual
Phase
Planned
Analyses
V-2
Kinetic glucose utilization
V1stress pre
V0
V2 & post challenge
V3
V4
Oxidative
Dietary and nutritional status
Flexible
4 weeks
Circadian rhythmicity
Metabolomics, proteomics, lipidomics
Health symptoms sub-typing
* Detailed
Menstrual Phase Schema
Behavioral sub-typing
+
V-1
V5
V6
V7
V8
V9
V10
n=
30 Females
1 mo
3 months
F1
F1 = Follicular
phase wk 1
Age = 30 – 45 years
F2 = Follicular phase wk 2
BMI = 25 – 35 kg/m2
L1 = Luteal phase wk 1
L2 = Luteal phase wk 2
Kinemed Kinetics
Measure then classify – Discovery science using systems approach (aggregated n-of-1)
What are the biological differences between Heat
and Cold in RA?
Parameter
Warm, swollen & red joint scores (3 or more
symptoms)
Source
Heat
Cold
Translation
63% patients
5% patients
Heat = greater disease severity.
Symptoms ques
Higher
Anti-citrullinated protein antibody (CCP)
Serum
IgG
Serum
Blood urea nitrogen (BUN)
Plasma
Acylcarnitines
Pantothenic acid
Heat = advanced disease progression.
Higher
Cold = High levels of antibodies = heightened immune response.
Higher or lower
Avg
Heat = higher risk of kidney damage
Higher levels of 11
Lower
Cold = less muscle mass, more pronounced muscle breakdown, impaired fatty acid metabolism,higher fatigue. May benefit from
carnitine and acylcarnitine supplementation.
Lower
Cold = decreased activation of peroxisome proliferator activated receptors (PPAR). Impaired macronutrient metabolism, such as,
in muscle.
Lower
Cold patients = Low levels, suppressed HPA-axis function = inadequate stress response, which is associated with autoimmune and
inflammatory disorders.
Urine
Urine
Higher
DHEAS
van Wietmarschen H et al. PloS One. 2012.
4 Fundamental Research Axes
Nestlé Institute of Health Sciences
•
•
•
•
Brain, Metabolic & GI Health; Ageing
Biomarkers, Mechanism of Action
Omics Technologies
Computational Sciences for Big Data (Systems Biology)
Nestlé Research Center
•
•
•
•
•
Nutrition & Health
Food Science & Technology
Sensory & Consumer Science
Quality & Safety
Analytical Sciences
•
•
•
Crop Yield
Plant Quality
Sustainability
•
•
•
•
Clinical Trials
Metabolic Unit
Data Management
Biostatistics
R&D Tours
Clinical Development Unit
© 2015 Nestlé
Health Science: Pioneering Science-based Targeted Nutrition
A biomedical research institute
dedicated to the development of
scientific methods and solutions to
improve health through nutrition
© 2015 Nestlé
A health-science company aiming
to foster a therapeutic role for
nutrition in healthcare
NMR Metabolomics Data
Metabolite
Lysine 1
Lysine 2
Alanine
Glutamine 1
Glutamine 2
Creatinine
Glycine
Serine
VLDL CH2
Hydroxybutyrate
Acetoacetate
Chemical shift (ppm)
Menstrual
Follicular
Periovulatory Luteal
PremenstrualP-value
1.73
1.69
1.49
1.47
1.32
1.49
0.008
1.75
1.44
1.29
1.25
1.03
1.17
0.001
1.49
5.58
5.19
5.25
4.4
6.08
0.007
2.45
3.33
2.71
2.67
2.53
3.03
0.007
2.47
5.4
5.41
5.49
4.67
5.54
0.019
3.07
3.67
3.55
3.27
3.09
3.35
0.05
3.57
13.99
13.44
13.36
12.81
15.05
0.033
3.97
2.59
2.46
2.27
2.04
2.23
0.002
1.29
30.47
31.56
32.99
35.75
33.28
0.013
1.23
6.4
6.84
6.48
7.06
6.63
0.625
2.05
14.6
14.79
15.26
16.19
15.75
0.014
Acetoacetate/Alanine Ratio
VLDL CH2/Alanine
Ratio
Metabolite
Lysine 1
Lysine 2
Alanine
Glutamine 1
Glutamine 2
Creatinine
Glycine
Serine
VLDL CH2
Hydroxybutyrate
Acetoacetate
2.62
5.46
2.85
6.08
2.91
6.28
Menstrual Err Follicular Err Periovulatory Err
Luteal
0.4
0.32
0.41
0.38
0.4
0.36
1.5
1.49
1.69
1.16
0.76
0.94
1.04
0.92
1.07
0.79
0.78
0.53
2.18
2.18
2.36
0.57
0.61
0.36
5.87
6.96
6.72
1.26
1.95
1.85
2.04
2.57
2.89
3.68
8.13
2.59
5.47
0.625
0.014
Err Premenst Err
0.4
0.21
0.43
0.29
0.98
1.62
0.71
0.45
1.06
0.56
0.85
0.34
1.94
1.52
0.56
0.31
9.37
4.83
1.85
0.91
2.68
1.92
Wallace M., etal. Hum Reprod Advance Access, February 10, 2010
38
Game-changing breakthroughs that advanced treatment of human disease:
• Insulin therapy
• Smallpox vaccine development
• First HIV cure
“Initial studies were carried out in single subjects or families and a larger n
would not have been much more persuasive.”
Diet Intake and Assessment Tools
What are they? What do they do? What is the situation?
•
Capture data
• 24 hour recall
•
Analyze food to
nutrients
• Diet diary
•
Report results
• Food Frequency Questionnaire
•
Compare to
requirements
•
Score results
Integrated Scientific Approach: the interplay between…
NIHS is committed to
developing solutions for
maintaining health and
lowering the overall disease
burden
Diet
Genes
We do this through pioneering
fundamental research, based
on integrated scientific
approach, focus on
generating translatable
knowledge and concepts
© 2015 Nestlé
Lifestyle
42