Interaction between the gut and its microbiota in inflammatory bowel disease

Mehdi Sadaghian

    Research output: ThesisThesis fully internal (DIV)

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    Abstract

    Interaction between the gut and its microbiota in inflammatory bowel disease
    The human gut microbiome is a crucial factor in the pathogenesis of inflammatory bowel disease (IBD), i.e.Crohn’s disease and ulcerative colitis. The gut microbial composition of IBD patients and healthy volunteers is different, containing more pathosymbionts, like Escherichia coli, and less commensal bacteria, like Faecalibacterium prausnitzii. We studied the ecology and immunology of the abundant gut commensal F. prausnitzii to unravel the interaction between the microbiota and the host. Furthermore, the influence of genetics and immunology on the mucosal microbiota in IBD patients was studied.
    Our results described the existence of at least three different phylogroups of F. prausnitzii, one of which colonizes specific food particles together with other main members of gut microbiota. Daily consumption of riboflavin (vitamin B2) increased the number F. prausnitzii and other beneficial bacteria in the gut. Living F. prausnitzii were shown to suppress inflammation in a novel coculture system that allows simultaneous growth of anaerobic bacteria and aerobic gut epithelial cells. Studying the relation between genetic factors and mucosal microbiota showed that the Crohn’s disease-associated risk variant of ATG16L1 impairs proper clearance of pathosymbionts in inflamed tissue. Analyzing the IgG binding capacities of the gut microbiota of IBD patients showed that their humoral immune response is primarily directed against small intestinal bacteria and pathosymbionts and not to commensal bacteria. Our data provide new options for studying and treating inflammatory bowel disease through dietary or pharmacological manipulation of the gut microbiome.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Dijkstra, Gerard, Supervisor
    • Faber, Klaas Nico, Supervisor
    • Harmsen, Hermie J.M. , Co-supervisor
    • Rijkers, Ger T., Assessment committee, External person
    • Flint, HJ, Assessment committee, External person
    • Bos, Nico, Assessment committee
    Award date11-Mar-2015
    Place of Publication[S.l.]
    Publisher
    Print ISBNs978-94-6299-034-0
    Publication statusPublished - 2015

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