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Trial Lecture – time and place
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Adjudication committee
- First opponent: Professor Rinse Weersma, University of Groeningen,
- Second opponent: Docent Reetta Satokari, University of Helsinki,
- Third member and chair of the evaluation committee: Professor Espen Haavardsholm, University of Oslo
Chair of the Defence
Associate Professor Kristian Tonby, University of Oslo
Principal Supervisor
Professor Johannes Espolin Roksund Hov, University of Oslo
Summary
Inflammatory bowel disease (IBD) affects more than 10 million people worldwide, and this number is rapidly increasing in newly industrialized countries. IBD represents a disease typically not seen in rural or poor areas, but is rather associated with urban, Western and modern lifestyles, and is thus paradoxically a negative consequence of improving the standard of living for people across the globe. Once a person develops IBD, it is a lifelong and chronic condition characterized by a multitude of symptoms decreasing quality of life, and current treatment efforts are focused on reducing symptoms and preventing complications by inducing and maintaining remission. The disease encompasses two or more categories or subtypes, including ulcerative colitis (UC) and Crohn’s disease (CD). Within each subtype the presentation can be both phenotypically and temporally varied, and overall IBD is regarded as an exceptionally heterogeneous disease, which in turn produces clinical challenges related to diagnostics, prognostics and choice of treatment.
In this thesis, I present and discuss the results and implications from four Papers based on two separate prospective IBD cohorts (IBSEN III and IBD-Character). In these Papers, we attempt to address the potential utility of the microbiome as a noninvasive marker in IBD diagnostics and prognostics. Specific outcomes examined include differentiating IBD from symptomatic non-IBD controls, distinguishing indolent from severe disease courses, and identifying phenotypic subgroups within IBD, such as UC versus CD, as well as disease location-specific subtypes like ileal CD, colonic CD, proctitis UC, and extensive UC.
Overall, we found limited value of the microbiome as a general marker of IBD from symptomatically similar controls, since already established inflammatory markers like fecal calprotectin consistently outperformed microbiome profiles in this regard. However, there were consistent and relatively strong signals related within-IBD phenotypic characterization. We described a novel microbial index which could both separate CD from UC, as well as indicate disease location. We validated the index in a separate pediatric in-house cohort, and crucially also in an international validation cohort from three continents (North America, Europe and Asia). In all continents, the index was significantly different between CD and UC.
Furthermore, we showed that microbiome markers are related to future disease development, and crucially we demonstrated both through supervised and unsupervised methods that this association remains when controlling for baseline disease severity. In short, those headed for a severe disease course tended to have a reduced diversity of Firmicutes, a phylum of bacteria containing many bacterial species important for proper gut function. On the other hand, participants with a particularly high risk of a severe disease course had a combined reduction of Firmicutes with a simultaneous overabundance of pro-inflammatory bacteria like Ruminococcus gnavus.
Overall, we have shown that the microbiome can bring significant value to future clinical workflows, both related to IBD diagnostics and prognostics, while acknowledging that our results show a variability and stochasticity which indicates that the microbiome in itself may be unsuitable for standalone tests. Rather, future efforts should aim to incorporate these signals into multifaceted models, so the ultimate aim of precise personalized clinical decision-making can be achieved, thus improving the lives of those with IBD.
Additional information
Contact the research support staff.