Introduction

The incidence and prevalence of Inflammatory Bowel Disease (IBD) are progressively increasing worldwide, particularly in developing countries. Despite increasing awareness of IBD and improvements in biomarkers and diagnostic techniques, a significant diagnostic delay is still frequently observed. This is highly relevant as diagnostic delay prevents application of medical treatment during very early disease stages and the implementation of certain disease intervention strategies. Diagnostic delay is consequently still limiting our potential to alter the natural history of the disease, as has recently been shown by UK colleagues. In a systematic review and meta-analysis, it was demonstrated that individuals with Crohn’s Disease (CD) in the higher quartiles of diagnostic delay (median 24 months) were more likely to have stricturing or penetrating disease and were also more likely to undergo intestinal surgery, while in patients with Ulcerative Colitis (UC) such a delay was associated with increased probability of colectomy [1]. Hence, reducing diagnostic delay should be a priority if we are aiming to apply effective disease intervention strategies.

Tanja Kuehbacher © ECCO

In the fast-paced world of medical research and drug development, efficient data management and transparent communication are critical factors for success. To address these challenges, the European Medicines Agency (EMA) has launched a new Clinical Trials Information System (CTIS) that went live on January 31, 2022 [1, 2]. The CTIS is the backbone of the Clinical Trials Regulation, which will harmonise the assessment and supervision of clinical trials in the European Union. There is a transition period until January 31, 2025. Any ongoing trial that has been approved under the Clinical Trial Directive will then fall under the Clinical Trials Regulation [1–3].

Gabriele Dragoni © ECCO

After repeated postponements due to travel restrictions to Japan, I was able to carry out enteroscopy training at the Tokyo Medical and Dental University (TMDU) Hospital between September and October 2022.

Induction of circadian microbial function in chronic intestinal inflammation

Silke Kiessling © Silke Kiessling

Background & aim of research

Impaired clock gene expression has been observed in biopsies from patients with Inflammatory Bowel Disease (IBD). Disruption of circadian rhythms, which occurs in shift workers, has been linked to an increased risk of gastrointestinal diseases, including IBD. The intestinal clock balances gastrointestinal homeostasis by regulating the microbiome. We aimed to characterise intestinal immune functions in mice lacking the intestinal clock and in IBD-relevant mouse models under different feeding conditions in order to assess the functional impact of the intestinal clock in the development of gastrointestinal inflammation.

Investigating the genetics of IBD multiplex families

Ho-Su Lee © Ho-Su Lee

Background & aim of research

This research aimed to investigate the genetic architecture of Inflammatory Bowel Disease (IBD) multiplex families (including at least three affected first-degree relatives), and to identify the underlying genetic factors that contribute to the familial aggregation of IBD.

Role of DNA methYlation and geNe expression alterations in development of eArly-onset priMary sclerosIng cholangitis in ulCerative colitis – DYNAMIC

Sudipto Das © Sudipto Das

Background & aim of research

Primary Sclerosing Cholangitis (PSC) is a progressive choleostatic disease and up to 80% of patients also have Ulcerative Colitis (PSC-UC). This presents a clinical challenge owing to the diagnostic difficulty and the increased risk for development of cancer. The aim of this study was to identify the transcriptomic and epigenetic alterations regulating the phenotype of this disease.

The role of autophagy in limiting IBD-associated AIEC-induced intestinal inflammation

Shai Bel © Shai Bel

Background & aim of research

While the aetiology underlying the development of Inflammatory Bowel Diseases (IBD) is unclear, evidence points to an interaction between host genetics, such as mutations in autophagy genes, and environmental factors, such as bacterial infections. Multiple studies have identified an adherent-invasive Escherichia coli pathotype (AIEC) only in patients with IBD. It is thought that AIEC exploits the intestinal inflammation in patients with IBD to attach to intestinal epithelial cells, intensifying the pre-existing inflammation. Studies in vitro have shown that functional autophagy is crucial to eliminate AIEC infection. Here, we aimed to identify how autophagy protects the host from AIEC-associated pathologies in vivo.

Marc Ferrante © ECCO

Yves Panis © ECCO

Pauline Rivière © Pauline Rivière

For two years, a group of 25 IBD specialists, including gastroenterologists, surgeons and scientists, have been working to build a research framework for postoperative recurrence (POR) in patients with Crohn’s Disease. Even though more biological therapies are now available, ileocaecal resection is still a frequent event and POR management remains a challenge for both patients and IBD specialists.

Robin Dart © ECCO

Iris Dotan is a gastroenterologist and mucosal immunologist based at Rabin Medical Center, Israel. She is chair of the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) and is well known to ECCO Members through her previous membership of SciCom, her speeches at ECCO Congress and her permanent presence on the Hearts and Minds dancefloor. During a break at the ECCO Congress in Copenhagen, I sat down with Iris to discuss her career, how mentorship has been important to her and, for anyone who has been on a Zoom call with her in the last 3 years, the origins of the beautiful painting she is usually seen sitting in front of.

Vedolizumab for the treatment of chronic pouchitis

Travis S, Silverberg MS, Danese S, et al., EARNEST Study Group

N Engl J Med 2023;388:1191–1200. doi:10.1056/NEJMoa2208450.

Introduction

Proctocolectomy is a curative treatment for medically refractory Ulcerative Colitis (UC). However, a significant number of patients prefer to have continuity of their bowel and undergo a restorative ileal pouch–anal anastomosis (IPAA), after having had an initial subtotal colectomy. Unfortunately, pouchitis is a most common complication in patients with an IPAA: 81% of patients experience pouchitis in their lifetime, with 40% experiencing it in their first year of pouch formation [1]. Multiple factors associated with pouchitis include mutations in NOD2/CARD15, genetic polymorphisms of interleukin-1 receptor antagonists [2–4], tumour necrosis factor allele 2 and toll-like receptor 1 [5].

The cause of pouchitis is multifactorial, including abnormal immune reaction to newly formed IPAA, change in the vascularity and anatomy of the bowel, faecal stasis and many other postulated factors. Single-cell analysis of CD45+ haematopoietic cells in the colon and pouch of UC patients has also highlighted genetic pathways that might contribute to the inflammation and disease severity seen in this condition [6]. However, the aetiology of pouchitis remains poorly understood and this may explain why treatment of this condition has emerged as an important area of unmet research need in the field of IBD. The treatment currently ranges from probiotics, antibiotics, steroids and immunomodulators through to use of biologics. Unfortunately, 50% of patients develop recurrent pouchitis, and up to 20% develop chronic pouchitis. Typically, cases of medically refractory pouchitis have been treated with anti-tumour necrosis factor (anti-TNF), vedolizumab and ustekinumab, but the evidence base for this approach has been very limited, typically comprising only case series and retrospective studies. Until recently, there had been no double-blind, randomised placebo-controlled trial supporting use of any therapeutic in pouchitis. Therefore, there has been significant interest in the study by Travis et al., reporting the first placebo-controlled trial for treatment of pouchitis, with use of vedolizumab. The findings from this trial help to provide evidence supporting the use of gut-selective vedolizumab for patients living with an IPAA.