Establishment of a multi-organ-on-chip model to advance gut-brain communication research and developmentrt

Laure Maes © Laure Maes

Background & aim of research

Persistent fatigue severely affects the quality of life of IBD patients and reduces their ability to work. Although IBD patients, even when in clinical remission, report fatigue as one of the most disabling symptoms of their chronic disease, disease management is often only focused on attenuating gastrointestinal symptoms. In order to develop effective therapeutic interventions, a better understanding of what is causing IBD-associated fatigue is required. Therefore, the goal of this project is to develop a human gut-blood-brain in vitro model to explore the impact of active and extinguished gut inflammation on brain and brain barrier function.

Identification of gut microbial strains contributing to chronic inflammation in human and mice

Bahtiyar Yilmaz © Bahtiyar Yilmaz

Background & aim of research

The relationship between host and microbiota can turn negative, leading to changes in microbial composition and metabolism that result in diseases such as Inflammatory Bowel Disease (IBD). Enteropathogenic strains increase due to the presence of reactive oxygen species in an altered metabolic environment. This study aims to understand how an IBD microbiota carrying an oxidative stress signature adapts over time and how these strains contribute to the disease's trajectory and fluctuations of oxidative stress in the outer mucus layer.

Aim 1: To isolate and characterise the capacity of freshly isolated human small and large intestinal microbial members contributing to oxidative stress.

Aim 2: To colonise germ-free or defined microbiota colonised mice with isolated bacterial strains to test their contributions and resilience to inflammation/oxidative stress in the mouse intestines.

Delineating an uptake-independent function of SR-BI in Paneth cells in metabolic gut inflammation

Felix Grabherr © Felix Grabherr

Background & aim of research

Dietary lipids are associated with risk of developing Inflammatory Bowel Disease (IBD). Activity of glutathione peroxidase 4 (GPX4), an anti-oxidative selenoenzyme, is impaired in intestinal epithelial cells (IECs) from patients with ileal Crohn’s Disease (CD). GPX4 controls intestinal inflammation triggered by dietary polyunsaturated fatty acids (PUFAs) and dietary PUFA uptake is associated with CD flares. SR-BI (encoded by Scarb1) is a membrane-bound receptor, mainly reported to be involved in the uptake of cholesterol, and cholesterol uptake has been described to play a role in ferroptosis induction, a cell death pathway which is regulated by GPX4. Paneth cells (PCs), specialised IECs within the small intestine, have been described to be the origin of intestinal inflammation. Preliminary data indicate that PCs sense and translate dietary PUFA stress into intestinal inflammation. 

Deciphering of composition and characteristics of intra- and peritumoral immune cells in human IBD-associated dysplasia and cancer using novel spatial profiling techniques

Sofía Frigerio © Sofía Frigerio

Background & aim of research

Chronic colonic inflammation in patients with Inflammatory Bowel Disease increases the risk of colitis-associated cancer (CAC). Although mouse studies have been instrumental in understanding CAC development, the immune cell composition and the role of these immune cells in human CAC are largely unknown.

In this study, we aim to decipher the composition and characteristics of immune cells in close proximity to dysplastic pre-cancerous lesions and cancers in IBD patients, and to decipher possible interactions between epithelial cells and the underlying immune cell populations in these regions, using novel spatial profiling techniques.

Identifying biomarkers prior to IBD diagnosis from the Prospective Urban Rural Epidemiology Study (PURE-IBD)

Neeraj Narula © Neeraj Narula

Background & aim of research

The primary objective of this study is to identify novel serum biomarkers prior to IBD onset that may mediate IBD risk in PURE.

Peter Bossuyt © ECCO

Designing, organising and performing clinical trials in IBD is a challenge. Drug development trials often follow the well-known pathways, with established endpoints and a more or less standardised study design. Things become more complicated when the clinical researcher departs from these trusted routes.  In this context, ClinCom (the Clinical Research Committee of ECCO) organised two courses during the last ECCO Congress in Copenhagen.

A total of 74 epidemiological abstracts and 18 digital oral presentations were presented at ECCO'23 in Copenhagen. Five abstracts of particular interest are discussed below.

A novel population-based UK study by Cooney and colleagues (OP 28) examined the association of IBD and various mental health disorders such as depression, anxiety and self-harm in children and adolescents. A large primary care database was used to identify cases. Each case was propensity matched with four controls. Relative risk of all outcomes up to 10 years in the IBD cohort versus controls was estimated using adjusted Cox proportional hazards models controlling for age, sex, socioeconomic status, ethnicity and other conditions. A total of 3898 young patients with incident IBD were matched to 15,571 controls. IBD patients were significantly more likely to develop PTSD [adjusted hazard ratio (aHR) 2.47, 95% CI 1.23–4.94], eating disorders (aHR 1.85, 95% CI 1.05–3.26), self-harm (aHR 1.49, 95% CI 1.00–2.21), sleep disturbance (aHR 1.40, 95% CI 1.15–1.71), depression (aHR 1.34, 95% CI 1.16–1.56) and anxiety disorder (aHR 1.25, 95% CI 1.06–1.48). These findings highlight the need to screen for these conditions in young patients.

A total of 74 epidemiological abstracts and 18 digital oral presentations were presented at ECCO'23 in Copenhagen. Five abstracts of particular interest are discussed below.

A novel population-based UK study by Cooney and colleagues (OP 28) examined the association of IBD and various mental health disorders such as depression, anxiety and self-harm in children and adolescents. A large primary care database was used to identify cases. Each case was propensity matched with four controls. Relative risk of all outcomes up to 10 years in the IBD cohort versus controls was estimated using adjusted Cox proportional hazards models controlling for age, sex, socioeconomic status, ethnicity and other conditions. A total of 3898 young patients with incident IBD were matched to 15,571 controls. IBD patients were significantly more likely to develop PTSD [adjusted hazard ratio (aHR) 2.47, 95% CI 1.23–4.94], eating disorders (aHR 1.85, 95% CI 1.05–3.26), self-harm (aHR 1.49, 95% CI 1.00–2.21), sleep disturbance (aHR 1.40, 95% CI 1.15–1.71), depression (aHR 1.34, 95% CI 1.16–1.56) and anxiety disorder (aHR 1.25, 95% CI 1.06–1.48). These findings highlight the need to screen for these conditions in young patients.

Ultrasound and MRI Portion

Mariangela Allocca © ECCO

Uri Kopylov © ECCO

The 4^th ECCO Basic Imaging Workshop in collaboration with ESGAR & IBUS opened with two introductory lectures on what to look for in intestinal ultrasound (IUS) and magnetic resonance imaging (MRI), given by Christian Maaser (Germany) and Pasquale Paolantonio (Italy), respectively. These lectures introduced the hands-on part of the workshop. Delegates (n=60 in the morning and 60 in the afternoon session) were subdivided into small groups at 12 different stations, where, with the support of expert tutors – one radiologist and one gastroenterologist – they interactively discussed MRI exams and performed sonographic evaluations, employing hands-on IUS simulators on different IBD cases.

Mariangela Allocca  © ECCO

Finally, after a hiatus of two years owing to the global COVID-19 pandemic, the 10^th ECCO Ultrasound Workshop – Advanced in collaboration with ESGAR & IBUS took place physically at ECCO’23 in Copenhagen.