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In this thesis, I hypothesized that microbial dysbiosis, through its interactions with host genetics and environment, can dysregulate human metabolism and contribute to an individual’s risk of developing complex disease. To test this hypothesis, I made use of various layers of “omics” datasets (metagenomics, metabolomics and genetics) in combination with the extensive phenotypic information that has been generated for a unique series of population- based prospective cohorts and patient cohorts, including Lifelines-DEEP, 500FG, 300OB and 1000IBD. Firstly, I linked the gut microbiome to host plasma metabolites generated by various platforms and showed that the gut microbiome can explain a substantial proportion of inter-individual metabolite variations. Secondly, we assessed genetics-microbiome- diet interactions in the control of plasma metabolite concentrations to reveal their role in metabolic dysregulation and their relevance to human health and disease. Furthermore, I applied statistical models to infer causal relationships between the gut microbiome and plasma metabolite concentrations. I was able to show that the gut microbiome may causally contribute to host phenotypes via the regulation of plasma metabolites. Additionally, I inferred microbial interactions through co-abundance analysis and characterized many IBD- and obesity-specific microbial interactions that pinpoint key microbial species and pathways in these diseases. Overall, the findings reported in this thesis have extended our understanding of the role of environment-genetics-microbiome interactions in the development of complex disease, and this knowledge will ultimately contribute to better therapeutic treatment options for these complex diseases.
Originele taal-2English
KwalificatieDoctor of Philosophy
Toekennende instantie
  • Rijksuniversiteit Groningen
  • Yang-Fu, Jingyuan, Supervisor
  • Kuipers, Folkert, Supervisor
  • Zhernakova, Sasha, Supervisor
Datum van toekenning22-jun-2021
Plaats van publicatie[Groningen]
StatusPublished - 22-jun-2021

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