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Environment-host-microbe interactions shape human metabolism

PhD ceremony:Mr L. (Lianmin) Chen
When:June 22, 2021
Supervisors:prof. dr. J. (Jingyuan) Yang-Fu, prof. dr. F. (Folkert) Kuipers, prof. dr. A.P. (Alexandra/Sasha) Zhernakova
Where:Academy building RUG
Faculty:Medical Sciences / UMCG
Environment-host-microbe interactions shape human metabolism

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.