Now in a revised second edition,Nutrigenomics and Proteomics in Health and Disease brings together the very latest science based upon nutrigenomics and proteomics in food and health. Coverage includes many important nutraceuticals and their impact on gene interaction and health. Authored by an international team of multidisciplinary researchers, this book acquaints food and nutrition professionals with these new fields of nutrition research and conveys the state of the science to date.

Thoroughly updated to reflect the most current developments in the field, the second edition includes six new chapters covering gut health and the personal microbiome; gut microbe-derived bioactive metabolites; proteomics and peptidomics in nutrition; gene selection for nutrigenomic studies; gene-nutrient network analysis, and nutrigenomics to nutritional systems biology. An additional five chapters have also been significantly remodelled. The new text includes a rethinking of in vitro and in vivo models with regard to their translatability into human phenotypes, and normative science methods and approaches have been complemented by more comprehensive systems biology-based investigations, deploying a multitude of omic platforms in an integrated fashion. Innovative tools and methods for statistical treatment and biological network analysis are also now included.

About the Editors

Martin Kussmann is Professor of "Systems Biology in Nutrition and Health" at the Liggins Institute, University of Auckland, New Zealand. He is also Chief Scientist of New Zealand's National Science Challenge "High-Value Nutrition". In 2011, Martin joined the Nestlè Institute of Health Sciences (NIHS) on the campus of the Ecole Polytechnique Fèdèrale Lausanne (EPFL), Switzerland, as Head of the "Molecular Biomarkers Core". From 2012 to 2016, he has been Lecturer at the Faculty of Life Sciences, EPFL. Since June 2009, Martin is Honorary Professor for Nutritional Science at the Faculty of Science, Aarhus University, Denmark. He holds a MSc and PhD in Chemistry from the University of Konstanz, Germany.

Patrick J. Stover is Professor and Director of the Division of Nutritional Sciences at Cornell University. He graduated from Saint Joseph's University with a BS degree in Chemistry, and received a PhD degree in Biochemistry and Molecular Biophysics from the Medical College of Virginia, and performed his postdoctoral studies in Nutritional Sciences at the University of California at Berkeley.

Contributors x

Preface xiii

Biography of Martin Kussmann xiv

Section I Genes, Proteins, and Nutrition 1

1 The use of transcriptomics as a tool to identify differences in the response to diet 3
Juri C. Matualatupauw and Lydia A. Afman

1.1 New concepts in nutrition research 3

1.2 Comprehensive phenotyping 3

1.3 Phenotypic flexibility 4

1.4 Factors that influence the transcriptome response to diet 5

1.5 Using transcriptomics to explain mechanism behind differences in response to diet 10

1.6 Conclusion 10

1.7 Future perspectives 15

References 16

2 Genetic or nutritional disturbances in folate?]related pathways and epigenetic interactions 19
Daniel Leclerc and Rima Rozen

2.1 Introduction 19

2.2 Nutrition and one?]carbon metabolism 20

2.3 Importance of DNAmethylation at CpG dinucleotides 23

2.4 Folate?]dependent disorders: Dietary impact 24

2.5 Genetic influences on phenotype and interactions with epigenetics 27

2.6 Epigenetic inheritance across generations 31

2.7 Conclusions 34

References 35

3 Early?]life development and epigenetic mechanisms: Mediators of metabolic programming and obesity risk 42
Felicia M. Low, Peter D. Gluckman, and Keith M. Godfrey

3.1 Introduction 42

3.2 Origins of DOHaD and its conceptual basis 43

3.3 Epigenetic mechanisms 44

3.4 Early?]life nutrition, epigenetics, and metabolic programming 48

3.5 Paternal effects 52

3.6 Transgenerational epigenetic inheritance 54

3.7 The potential value of DOHaD principles and epigenetic biology to the improvement of human health 55

3.8 Conclusion 57

Acknowledgments 57

References 58

Section II Bioactives and Phytonutrients 65

4 Bioactive interactions in food and natural extracts 67
Sofia Moco and Denis Barron

4.1 Natural compounds as all compounds produced by nature 67

4.2 Not all natural compounds are created active 70

4.3 On the road of modern technologies for bioactive discovery 71

4.4 Metabolomics strategies applied to bioactives biochemistry 77

4.5 Bioactives as multi?]target network instigators 81

4.6 Let food be thy medicine and medicine be thy food outlook 85

Acknowledgments 85

References 85

5 Anthocyanins in metabolic health and disease 92
John Overall, Mary Ann Lila, and Slavko Komarnytsky

5.1 Introduction 92

5.2 Chemical structure 93

5.3 Structural effects on stability 93

5.4 Systemic bioavailability and tissue distribution 96

5.5 Metabolism and nutrigenomic effects 102

5.6 Conclusions 114

Acknowledgments 114

References 114

6 Dietary antioxidants and bioflavonoids in atherosclerosis and angiogenesis 125
Mohsen Meydani and Angelo Azzi

6.1 Introduction 125

6.2 Dietary vitamins E and C and CVD 126

6.3 Dietary polyphenols and CVD 128

6.4 Flavonoids and angiogenesis 134

6.5 Conclusion 135

Acknowledgments 136

References 137

7 Genomics and proteomics approaches to identify resveratrol targets in cancer 143
César López?]Camarillo, Rubiceli Medina?]Aguilar, Carlos Palma?]Flores, and Laurence A. Marchat

7.1 Introduction 143

7.2 Sources and health benefits of resveratrol 144

7.3 Resveratrol for cancer prevention and therapy 145

7.4 Functional genomics approaches to identify resveratrol targets in cancer 147

7.5 Proteomics approaches to identify resveratrol targets in cancer 148

7.6 Metabolomics approaches to identify pathways modified by resveratrol in cancer 150

7.7 Epigenomic events induced by resveratrol in cancer 152

7.8 Conclusions and perspectives 153

References 153

8 Genomic effects of food bioactives in neuroprotection 156
Ashraf Virmani, Syed Ali, Luigi Pinto, Saf Zerelli, and Zbigniew Binienda

8.1 Introduction: Nature and nurture 156

8.2 Mechanism underlying food nurture 156

8.3 Natural cellular nurture mechanisms 157

8.4 Effects of food bioactives on genomic activity 158

8.5 Epigenetic modulation 158

8.6 Modulation of the epigenome by food bioactives 159

8.7 Possible role of the genome in neuroprotection 160

8.8 Countering risk factors associated with neurodegeneration 161

8.9 Using food bioactives to restore epigenetic balance 161

8.10 Targeting inflammation, energy, and free radicals 161

8.11 Food bioactives that reduce inflammation 163

8.12 Food bioactive effects on bioenergetics and redox balance 163

8.13 Role of food bioactive acetyl?]l?]carnitine in neurodegeneration 163

8.14 Process of S?]palmitoylation and the role of carnitine palmitoyltransferase 1c enzyme in the brain 164

8.15 Conclusion 164

References 165

9 MicroRNAs: Bioactive molecules at the nexus of nutrition and disease 170
Lisa M. Farmer and Kendal D. Hirschi

9.1 Introduction to micro RNAs as dietary bioactive compounds 170

9.2 Characteristics, biogenesis, and functions of miRNAs 171

9.3 miRNA detection methods 173

9.4 Small RNAs in the circulation 174

9.5 Endogenous miRNAs and metabolic control 176

9.6 miRNAs as biomarkers for diet and disease 178

9.7 Absorption of dietary animal miRNAs in animal consumers 184

9.8 Absorption of dietary plant miRNAs in animal consumers 185

9.9 Contradictory evidence of dietary miRNA uptake 188

9.10 Therapeutic potential of miRNAs 190

9.11 Gut pathology may influence dietary miRNA uptake 191

9.12 Conclusion 193

Acknowledgments 195

References 195

Section III Prebiotics, Probiotics, Synbiotics, and the Gut Ecosystem 201

10 Gut health and the personal microbiome 203
Carolin A. Kolmeder and Willem M. de Vos

10.1 Gut health and its concepts 203

10.2 Microbiome and gut health from composition to function 206

10.3 The personalized microbiome towards precision nutrition 211

10.4 Conclusions and next?]generation interventions 214

Acknowledgments 215

References 215

11 Infant nutrition and the microbiome: Systems biology approaches to uncovering hostmicrobe interactions 220
Mei Wang, Ivan Ivanov, Laurie A. Davidson,Robert S. Chapkin, and Sharon M. Donovan

11.1 Introduction 220

11.2 Environmental factors influencing development of the infant gut microbiota 221

11.3 Infant nutrition and the development of gut microbiota 223

11.4 Host genetics and the development of gut microbiota 226

11.5 Hostmicrobe interactions regulating host phenotype and gene expression 230

11.6 Systems biology approaches to diet?]dependent hostmicrobe interaction 243

11.7 Summary and conclusions 247

References 247

12 Bioactive hostmicrobial metabolites in human nutrition with a focus on aromatic amino acid co?]metabolism 258
François?]Pierre J. Martin and Martin Kussmann

12.1 Introduction: Gut microbiota metabolism in nutrition, health and disease 258

12.2 Short?]chain fatty acid metabolism 259

12.3 Bile acid metabolism 260

12.4 Aromatic amino acid metabolism 261

12.5 Conclusions and perspectives 269

References 270

Section IV Nutrigenomic and Proteomic Technologies 275

13 Network analysis in systems nutrition 277
Marie?]Pier Scott-Boyer and Corrado Priami

13.1 Introduction 277

13.2 Biological networks 278

13.3 Network topology 281

13.4 A general framework for network analysis of throughput data 282

13.5 Examples of network analyses 284

13.6 Conclusions and perspectives 286

References 287

14 Nutrigenomics analyses: Biostatistics and systems biology approaches 290
Damien Valour and Bernard Valour

14.1 Gene selection for nutrigenomics studies 290

14.2 Specificity of high?]dimension data and preprocessing before gene selection 291

14.3 Exploratory and differential gene expression analysis 292

14.4 Biomarker discovery in nutrigenomics: Gene selection and discrimination 297

14.5 A step towards data integration: searching for correlation/covariance between two datasets 310

14.6 From gene selection to systems biology 313

References 315

Index 319