Metabolomics for Food Composition and Food Biomarker and Food Biomarker Analysis ... determination of the chemical (metabolite) ... Composition Project

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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

    1234567ppm

    Biological or Tissue Samples Extraction Biofluids or Extracts

    Chemical AnalysisData Analysis

    http://groningen.bio.ucalgary.ca/bio/img/700.jpg

  • Metabolomics Technologies

    UPLC, HPLC

    CE/microfluidics

    GC-MS

    LC-MS

    LC-MS/MS

    ICP-MS

    NMR spectroscopy

    X-ray crystallography

    FTIR

    http://groningen.bio.ucalgary.ca/bio/img/700.jpg

  • Compound ID by GC/LC-MS

    LC/GC-MS total

    Ion chromatogram

    CH3

  • Compound ID by NMR

    http://bayesil.ca

  • 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

    1234567ppm

    Food Samples Extraction Food Extracts

    Chemical AnalysisData Analysis

    http://groningen.bio.ucalgary.ca/bio/img/700.jpg

  • 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

    http://groningen.bio.ucalgary.ca/bio/img/700.jpg

  • 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 10s for conventional methods

  • The Rush to Metabolomics

  • WineScreener & JuiceScreener

    Bruker BioSpin ($600,000)

  • 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 100s 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

  • Data Summary (Non-lipid

    Components)

  • 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

  • Alberta Food Composition Database

    www.afcdb.ca

  • 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

  • Food & Food Biomarkers

  • Metabolomics for Food

    Biomarkers

    1234567ppm

    Metabolism Biofluids

    Chemical AnalysisData Analysis

    Food Samples

    http://groningen.bio.ucalgary.ca/bio/img/700.jpg

  • 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

  • Food Biomarker Alliance

    http://foodmetabolome.org

  • 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

    1000s 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

  • Acknowledgements

    Augustin Scalbert

    Claudine Manach

    Rosa Vazquez Fresno

    Shima Borzouie

    Rupa Mandal

    Allison Pon