Hengameh Chloé Mirsepasi-Lauridsen:
Inflammatory Bowel Disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, traditionally divided into Crohn’s disease (CD) and ulcerative colitis (UC). UC is a relapsing non-transmural chronic inflammatory disease that is restricted to the colon and during flares the disease is characterised by bloody diarrhoea. CD is a chronic, segmental localised granulomatous disease that can affect any part of the entire gastrointestinal tract from the mouth to the anus. The aetiology of IBD is still unknown, but studies indicate several possible aetiologies such as the host immune system and influence of the gastrointestinal microbiota.
The gut microbiota of IBD patients contributes to initiation and/ or maintaining the inflammatory state by providing antigens or co-stimulatory factors that drive the immune response in a misdirection in these genetically susceptible hosts. Alterations in the makeup of the intestinal microbiota in IBD patients include a reduced diversity of intestinal microbial species in comparison to healthy controls, which is linked to the pathogenesis of IBD (Manuscript I). In addition, we showed that highest amount of DNA from the stool was extracted using manual Qiagen in comparison to semi-automated easyMag® method (Manuscript I). Bacteriological analysis of intestinal biopsies and faecal samples from UC patient show an increased number of Escherichia coli (E. coli) species in the B2 and D phylogenetic groups, harbouring O1, O2, O6, O18 and O75 antigens. These antigens are often expressed by the Extra-intestinal Pathogenic E. coli (ExPEC). Faecal calprotectin is a marker of gastrointestinal inflammation and is used in order to determine mucosal healing and disease relapses/ remission in IBD patients. Our study showed that CALPRO faecal calprotectin kit is most optimal method to analyse inflammation/ infection in IBD patients (Manuscript III). Patients colonized with E. coli from the B2 phylogenetic group display increased burdens of inflammation, as measured by colitis activity index (CAI) scores and faecal calprotectin levels, in comparison to patients not colonized with B2 E. coli (Manuscript IV). Previous studies have shown that the UC-associated E. coli strain p19A, which belongs to the B2 phylogenetic group and harbours ExPEC genes, induces cell death in dendritic cells, as well as stimulates the TNF-α, IL-6 and IL-23 cytokine production (Poster 1). p19A harbours two alpha-hemolysin genes, which causes rapid loss of tight-junction integrity to monolayers of differentiated Caco2 cells (manuscript II). These results suggest that IBD-associated E. coli might play a role in the pathophysiology of IBD.
In summary, this thesis presents original experimental data characterising IBD-associated E. coli in hopeful anticipation of inciting further interesting studies.