To Örebro University

Background: Inflammatory bowel disease (IBD) is a common and lifelong condition, but the phases of IBD development remain poorly understood.

Aims and methods: We aimed to characterise the distinct phases of IBD, encompassing (1) genetic predisposition, (2) preclinical disease, (3) diagnosis, (4) early disease course, and (5) established disease. To this end, we used twin methodology, proteomic profiling and characterisation of the gut microbiome.

Results: In Study I, the heritability was estimated to be 0.78 for Crohn’s disease (CD) and 0.57 for ulcerative colitis (UC). Study II identified protein signatures capable of predicting a future diagnosis of CD (area under the curve [AUC] = 0.77) and UC (AUC = 0.67). Study III revealed a restricted diagnostic potential of gut microbiome signatures for CD (AUC = 0.62) and UC (AUC = 0.59). Study IV yielded a risk score that could predict the future disease course of patients with newly diagnosed UC (AUC = 0.77). Study V was a longitudinal investigation of patients with ileal CD. We observed a negative correlation between temporal changes in the relative abundance of the commensal bacteria Faecalibacterium prausnitzii and changes in faecal calprotectin levels (R = -0.39; p = .009).

Conclusions:

1. A strong genetic predisposition to IBD is evident, with markedly higher heritability observed in CD relative to UC.

2. The circulating proteome can be used to prognosticate CD more than 16 years before its diagnosis.

3. The mucosa-associated gut microbiome's diagnostic capacity seems limited.

4. A proteomics-based risk score offers a means of predicting the early disease course of UC.

5. Temporal changes in the relative abundance of F. prausnitzii are associated with changes in inflammatory activity in ileal CD.