Deciphering the bioactive role of extracellular matrix fragments (matrikines) in Crohn's Disease (CD) fibrostenosis as potential therapeutic targets and biomarkers
To evaluate the in vitro effect of selected novel matrix-derived peptides (matrikines) that specifically appear in the intestinal tissue of patients with Crohn’s Disease (CD) fibrostenosis on primary human intestinal myofibroblasts (iMFBs).
Aim 1: To characterise the inter-/intra-individual composition of the mycobiome of patients with IBD and healthy controls utilising a variety of sample types and methodological techniques.
Aim 2: To provide a large dataset of fungal internal transcribed spacer (ITS) rRNA sequencing data to complement the bacterial 16S rRNA analysis underway in-house.
Multiple patient, disease and pharmacokinetic (including anti-TNF drug and antibody concentrations) factors, as well as a limited number of proteomic markers, have been implicated in anti-TNF treatment failure. However, their relative effects and interactions have not been fully explored. We aimed to replicate previously postulated serological markers and to identify novel inflammatory and immune response proteomic markers related to anti-TNF treatment failure in patients with active luminal Crohn’s Disease.
This project aimed to understand the effects that crucial IBD epithelial stress factors (i.e. ATG16L1 and XBP1 impairments) might have in enteric fibroblasts and neurons.
Tim Raine is a consultant gastroenterologist at Addenbrookes Hospital in Cambridge and an honorary faculty member of the Wellcome Trust Sanger Institute. He is a mucosal immunologist, and alongside translational science work, he is also heavily involved in clinical trials and guideline development. Despite his relative youth, Tim has been in and around ECCO for many years and is well known to the ECCO Community. After chairing both Y-ECCO and GuiCom, he is now a member of SciCom, reflecting the breadth of his involvement with IBD. I had the opportunity to discuss his work with ECCO and his journey into life as a clinician-scientist.
The Y-ECCO Mentorship Forum is an educational event designed to foster networking and prepare the career of young gastroenterologists with a particular interest in Inflammatory Bowel Disease. In June 2023, the second edition of the Forum took place in beautiful Vienna, and it certainly did not disappoint.
Biomarkers for the prediction of disease onset and disease course in Ulcerative Colitis (UC) represent an ongoing and important area of unmet need. However, discovery and validation of such biomarkers has been complicated by the wide heterogeneity in disease presentation and variability in disease course [1]. Despite many initial biomarker discovery efforts in UC focusing on biopsy-based approaches, it has increasingly been recognised that non-invasive blood-based biomarkers would likely have more clinical utility, including because of their ease of collection and high rates of patient acceptance [2, 3].
Previous studies have discovered a novel autoantibody against integrin αvβ6 (anti-αvβ6) in the serum of UC patients, with strong discriminative ability for diagnosis of UC. Integrin αvβ6 plays a critical role in maintaining epithelial barrier integrity and suppressing epithelial inflammation [4–7].
Faecal microbiota transplantation with anti-inflammatory diet (FMT-AID) followed by anti-inflammatory diet alone is effective in inducing and maintaining remission over 1 year in mild to moderate ulcerative colitis: a randomised controlled trial
Kedia S, Virmani S, Vuyyuru SK, et al.
Gut 2022;71:2401–13. doi: 10.1136/gutjnl-2022-327811.
Microbiota are known to play a role in the pathogenesis of both Ulcerative Colitis (UC) and Crohn’s Disease (CD). Various lifestyle factors, including rural living, absence of antibiotic exposure and larger family size, have been associated with greater microbial diversity and lower risk for development of IBD [1, 2]. Conversely, dietary patterns and constituent elements of the diet have been linked to dysbiosis and increased risk of IBD [3, 4]. Despite these associations, the causal relationship between microbiota disturbance and IBD pathogenesis/disease flares remains unclear.
Current therapeutic strategies for IBD primarily focus on targeting the dysregulated immune response. However, these approaches have limitations, including a “ceiling effect” of current treatments and a high risk of relapse following withdrawal of therapy [5]. Consequently, there has been a growing interest in exploring alternative interventions, including through modulation of the gut microbiota or manipulation of dietary factors. Most of the evidence for such therapeutic approaches has focused on CD, including with the use of exclusive enteral nutrition [6]. In UC, microbiota modification has been attempted by faecal microbiota transplantation (FMT) in cohort studies and in randomised controlled trials. However, heterogeneous protocols, methods, donors, doses and intervals of FMT have all likely contributed to the conflicting evidence base for FMT in UC. Notably, however, a recent meta-analysis has suggested an overall clinical and endoscopic benefit of FMT, at least in the short term, in the treatment of UC [7].
Despite an increasing number of therapeutic options for patients with Crohn's Disease (CD), one-third of individuals develop intolerance or lose response to current pharmacological treatments, and up to half of patients require surgery within ten years of diagnosis. One of the reasons often highlighted for such figures has been the increasing understanding that different sub-types of CD may require different treatment approaches. Indeed, multiple clinical and molecular studies in recent years have demonstrated the differences between ileal and colonic CD in terms of pathophysiological mechanisms [1], as well as clinical features such as disease progression and treatment efficacy. In fact, although there is a lack of reported data on the comparative efficacy of biologics in achieving segment-specific healing in CD [2], evidence from observational studies and post-hoc analyses of interventional trials has shown that deep ulcers in the ileum are more challenging to heal than those located in the colon [3], with rates of endoscopic healing after one year of therapy ranging from 19% to 38% [4].
I trust that you have all had at least some time for rest and relaxation over the summer. It has been an eventful time for the Y-ECCO Committee as well as the delegates and faculty who joined us for our second Y-ECCO Mentorship Forum in Vienna in July. I think it is fair to say that the event was a success, and we even managed a strike or two at the bowling ice-breaker event the evening before! If this sounds like something that may be of interest to you, I’d highly recommend reading the full write-up by Y-ECCO Committee Member, Gabriele Dragoni, in this edition of ECCO News. Our next Y-ECCO Mentorship Forum is planned for summer 2025 and, with your participation, it would be great to see the initiative continue to grow.
Robin Dart
Gabriele Dragoni
