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Metabolomics for Food
Composition and Food
Biomarker Analysis
David Wishart, University of Alberta
2017 ILSI North America FNSP Mid-Year Meeting
July 18, 2017 Arlington Virginia
Disclosures and Conflicts of Interest
I have no conflict of interest to
report in relation to this
presentation.
Funding
Some Definitions
• Metabolomics – The high throughput
analysis and characterization of the
chemicals constituting the metabolome
• Food Composition Analysis – The
determination of the chemical
(metabolite) components in food
• Food Biomarkers – Food components
or food metabolites found in the
metabolome that are characteristic of
specific foods
The Metabolomics Workflow
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Biological or Tissue Samples Extraction Biofluids or Extracts
Chemical AnalysisData Analysis
Metabolomics Technologies
• UPLC, HPLC
• CE/microfluidics
• GC-MS
• LC-MS
• LC-MS/MS
• ICP-MS
• NMR spectroscopy
• X-ray crystallography
• FTIR
Technology & Sensitivity
M mM M nM pM fM
# M
eta
bo
lite
s d
ete
cte
d (
Lo
g1
0)
0
1
2
3
4
Sensitivity or LDL
LC-MS or
DI-MS
NMR
GC-MS
Quad
GC-MS
TOF
Known unknowns
Unknown unknowns
Metabolomics for Food Analysis
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Food Samples Extraction Food Extracts
Chemical AnalysisData Analysis
Food Component Analysis
• Protein
• Fat
• Ash
• Minerals
• Carbohydrates
• Calories
• Water content
• Alanine
• Tryptophan
• Methyl-histidine
• PE(18:0/18:2)
• PE(16:0/18:1)
• TG(16:0/16:0/18:0)
• Phosphate
• Calcium
• Zinc
• Fructose
• Glucose
• N-acetylglucsoamine
• Apigenin
• Gallic acid
• Resveratrol
• Epigallocatechin Gallate
• Proline betaine
• …..
Traditional Metabolomics
Advantages of Metabolomics
• Applicable to food composition analysis
and food biomarker analysis
• Uses rapid, high throughput
methodologies (robotics, UPLC, MS/MS)
• Offers exquisite sensitivity (< 1 nM)
• Can be absolutely quantitative
• Can detect 100s to 1000s of compounds
vs. only 10’s for conventional methods
The Alberta Food
Composition Project• A 5 year metabolomics project aimed at
measuring the chemical composition of
~50 Alberta-grown food products (meat,
poultry, dairy, cereals, oils, vegetables
& fruits)
• Measuring 100’s of compounds via
quantitative metabolomics techniques
• Intent is to extend and validate
literature-based composition data and
identify candidate food biomarkers
Type Model
NMR Bruker 700 MHz cryoprobe & autosampler
NMR Varian/Agilent 600 MHz
ICP-MS Perkin Elmer NexION 350
GC-MS 2x Agilent 7890A GC-MS with autosampler
GC-MS Aglient/HP Series 5890 GC-MS
LC-MS Bruker 9.4T FT-ICR MS w. cap HPLC
LC-MS 2x ABI Qtrap 4000 MS w. Turbo ESI
LC-MS Agilent LC-ESI ToF MS
LC-MS 2x Bruker maXis II qTOF
HPLC Agilent w. Fluorescent detector
UPLC 2x Agilent 1290 Infinity UPLC
TMIC Overview
www.metabolomicscentre.ca
Using Multiple Platforms
Typical Results
• ~50 water-soluble metabolites by NMR
• ~80 compounds by DFI/LC-MS/MS via the
Biocrates AbsoluteIDQ™ kit
• ~400 lipids and fatty acids via GC-MS/LC-MS
• 53 trace elements by ICP-MS
• 48 small metabolites via GC-MS
• 17 polyphenols
• 9 water- and lipid-soluble vitamins
• Identification & quantification of ~600 cmpds
Metabolomics of Beet Root
HPLC NMR GCMS GCMS ICPMS DIMS Lipidomics(volatiles)
Po
lyp
he
nols
, vita
min
s,
ch
loro
phylls
, a
nth
ocya
nin
s
Org
an
ic a
cid
s, a
min
o a
cid
s,
am
ine
s, su
ga
rs, p
oly
ols
Org
an
ic a
cid
s, a
min
o,
acid
s, fa
tty a
cid
s
Vo
latile
org
an
ics, th
iols
,
ke
ton
es, e
ste
rs
Me
tals
Ca
rnitin
es, a
min
o a
cid
s,
ph
osp
ho
lipid
s, a
min
es
Ne
utr
al lip
ids, ch
ole
ste
rols
Ph
yto
ste
rols
, fa
tty a
cid
s
Num
bers
of Q
uantified C
om
pounds
METHOD
34 37
26
4138
85
~400
The Food Database (FooDB)
• 26,619 compounds, 25,579
structures with 24,843
descriptions
• 171,359 synonyms
• ~700,000 concentration values
• 31,791 references
• 1376 cmpds with health effects
• 2692 cmpds with flavour data
• Content data on 907 raw or
processed foods
• Supports structure & text
searches
• >100 data fields/compound
• Full data downloadswww.foodb.ca
Food & Food Biomarkers
• Data on food composition provides
important hints for potential food
biomarkers
• Food biomarkers need to be identified
to improve or corroborate findings
from food frequency questionnaires, 24
hr dietary recalls or food diaries
• Most food biomarkers are metabolites
of food components
Metabolomics for Food
Biomarkers
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Metabolism Biofluids
Chemical AnalysisData Analysis
Food Samples
Food
Metabolites/Biomarkers• Tea Epicatechin Benzoic acid Hippuric acid
• Meat Carnosine 1-Methylhistidine
• Eggs Lecithin Phosphocholine TMA TMAO
• Wine Ethanol Ethyl glucuronide
• Soy Daidzein Equol
• Onions Quercetin m-Hydroxyphenylacetate
• Anchovies Purines Uric acid
• Coffee Caffeine Theophylline Methylurate
• Grains Alkylresorcinols 3,5 Dihydroxybenzoate
The FoodBall Project
• A 4 year project (ends in 2018) to use
metabolomics to systematically identify and
validate food biomarkers
• 22 different partners in Holland, Belgium,
Ireland, Norway, Spain, Switzerland, France,
Denmark, Germany, Italy, Canada & ILSI
Europe working on diet intervention studies,
literature reviews, large cohort studies
• Funded by the EU & Canada (JPI-BioNH, CIHR)
• Goal is to make all the findings (and most
compounds) freely available
The Human Metabolome
Database (HMDB)• A web-accessible resource
containing detailed
information on 74,462
“quantified”, “detected” and
“expected” metabolites
• Includes many food
components & metabolites
• 1000’s of food additives
• >10,000 reference spectra
• Supports sequence, spectral,
structure and text searches as
well as compound browsing
• Major update for 2017http://www.hmdb.ca
Phenol-Explorer
• >900 peer-reviewed
papers, 37,000 data entries
• Content data on 502
polyphenols in 459
different plant foods
• >300 polyphenol
metabolites
• Data on food, food variety,
commercial origin,
extraction protocol,
analytical methods &
references
• Searchable by food name,
compound name or
polyphenol class
www.phenol-explorer.eu
Exposome-Explorer
• A database of dietary
and pollutant biomarkers
• 142 food/diet biomarkers
• 346 pollutant biomarkers
• >10,500 concentration
values in blood & urine
• From 480 publications
• Correlation values
• Supports text, structure
and concentration
searches
http://exposome-explorer.iarc.fr
Conclusions & Takeaways
• Metabolomics is transforming food
composition analysis
• Food composition databases have grown
considerably in depth and breadth thanks to
metabolomics
• Quantitative metabolomics is leading to the
identification of dozens of new and useful
food biomarkers
• Many of these findings are now freely
available on the web