Effects of early probiotic supplementation in a pediatric setting Focus on body composition, metabolism and inflammation

To my boys; Kristofer, Vidar & Ebbot " Knowledge is invariably a matter of degree: you cannot put your finger upon even the simplest datum and say 'this we know'. " T.S. Eliot " What day is it? " " It's today, " squeaked Piglet. " My favourite day, " said Pooh. Abstract iii Abbreviations v Original papers vi Populärvetenskaplig sammanfattning vii Bakgrund vii Syfte vii Studiepopulation och metod vii Resultat viii Slutsats ix Background 1 Personal point of departure 1 The obesity " epidemic " 1 Early programming 2 Gut microbiota 3 Establishment of the gut microbiota 4 The environment influences the intestinal colonization pattern 5 Classification of gut microbiota 5 Diet influences gut microbiota composition and functions 6 The gut microbiota and its potential role in the obesity " epidemic " 7 Systemic low-grade inflammation 8 Probiotics 9 Probiotic effects 10 Lactobacillus 11 Lactobacillus paracasei ssp paracasei F19 12 Probiotic studies in childhood 13 Long-term effects following early probiotic supplementation 13 Growth and body composition 15 Dietary assessment 16 Metabolomics 17 Multivariate data analysis 19 Objectives 21 Materials and methods 22 Study population and study design 22 The intervention study (Paper I) 22 The follow-up (Paper II-IV) 23 Data collection 23 Anthropometric measurements 23 Biochemical measurements 25 Metabolomic analysis 26 Dietary registration and nutritional calculation 26 Physical activity 27 Statistical methods 28 Results 29 Baseline characteristics 29 Growth, body composition and metabolic markers during weaning (Paper I) 31 Main results 32 Growth, body composition and metabolic markers at school age (Paper II) 33 Main results 36 Extended panel of metabolic and inflammatory markers (Paper III) 37 Main results 38 Long-term effects on the metabolome at 8-9 years of age (Paper IV) 39 Main results 41 ii Discussion 42 Main findings 42 Blood lipids and metabolomics 42 Growth and body composition 44 Adipose tissue and metabolic markers 44 Conclusion 45 Effects of probiotics 46 Modulation of the gut microbiota 46 A healthy microbiome 47 Methodological discussion 49 Comparison of animal and human studies 49 Metabolomics 50 Physical activity and energy/nutritional intake 50 Strengths and limitations 51 Future directions 53 Personal reflection 54 Acknowledgements 55 Funding 58 References 59 iii Abstract Background Once established, obesity and its health consequences are difficult to treat. An aberrant gut microbiota has been associated with several noncommunicable diseases, including obesity and its associated comorbidities. Probiotics, defined as " live microorganisms which, when administered in …