Suzanne van Zundert © Suzanne van Zundert

When mild to moderate Crohn’s Disease is diagnosed, various dietary approaches are used as a first-line medical treatment with a view to reducing inflammatory symptoms and achieving remission. It is important that this treatment is properly guided by a (paediatric) gastroenterologist and specialised nutritionist.

Jun Miyoshi  © Jun Miyoshi

Although I had to postpone my visit to Städtisches Klinikum Lüneburg due to the global COVID-19 outbreak, I was finally able to participate in intestinal ultrasound (IUS) training there in August to September 2022. I thank everyone involved in providing me with this great opportunity.

CCR6 blockade as novel therapeutic strategy against inflammatory bowel disease

Aim of the research

The CCL20/CCR6 axis is recognized as critical in IBD pathogenesis. However, CCR6 blockage has never been tested as therapeutic approach and no small-molecules CCR6 antagonists have been investigated as a potential anti-IBD drug candidates. Starting from our novel CCR6 antagonist (MR120), we aimed at: -designing and synthesizing more potent CCR6 antagonists; -identifying the most efficacious and tolerable anti-chemotactic CCR6 antagonist; -assessing the efficacy of MR120 and of the most promising novel derivative in adoptive transfer colitis (AT).

Fine determination of gut tissue layers' inflammation exploring immune-microbiota signatures: new biomarkers of recurrence in surgical patients with Crohn's disease?

Francesco Giudici © Francesco Giudici

Edda Russo © Edda Russo

Amedeo Amedei © Amedeo Amadei

Aim of the research

Up to 65% of patients with Crohn’s Disease (CD) show disease recurrence after ileocolic resection (ICR). The reasons for this high recurrence rate are still unclear, but the abnormal CD inflammatory process, supported by microbiota dysbiosis, affects all the intestinal wall layers. We explored the mutual interplay of inflammatory and microbial factors involved in CD through a systems-level study (tissue and systemic level), at the time of ICR, evaluating whether these specific factors are associated with CD recurrence.

Identification of markers to predict post-operative disease recurrence in Crohn's disease.

Salomé Pinho © Salomé Pinho

Harry Sokol © Harry Sokol

Background & aim of research

Evidence suggests that the perturbation of the symbiotic relationship between microbes and the intestinal immune system contributes to IBD development even years before diagnosis. However, it is essential to understand the causes underlying the loss of gut microbial equilibrium (dysbiosis) associated with inflammation, envisioning novel disease biomarkers and therapeutic targets. The host glycocalyx (repertoire of glycans/sugar-chains at the surface of gut mucosa) constitutes a major biological interface between intestinal mucosa and microorganisms. Glycans are an essential niche for microbiota colonization and thus should be an important modulator of host-microorganisms’ interactions and a key target in IBD context that remains largely unexplored. The GOAL of this proposal is to unlock the role of gut mucosa glycome as a novel pathway that regulates host-microbiome interactions in IBD, envisioning the development of novel microbial-modulating therapies for IBD prevention and treatment.

A prospective, open-label pilot study to evaluate effector mechanisms of hyperbaric oxygen therapy in patients with moderate to severe Ulcerative Colitis: the PARADOX study (exPlanAtoRy mechanisms in pAtients with moDerate-to-severe ulcerative colitis treated with hyperbaric OXygen therapy)

Joep van Oostrom © Joep van Oostrom

Krisztina B. Gecse © ECCO

Background & aim of research

Despite the increase in treatment options, there is still a group of Ulcerative Colitis (UC) patients who do not respond to drug treatment and ultimately require proctocolectomy. Recently, hyperbaric oxygen therapy (HBOT) was shown to be effective in difficult-to-treat UC patients, with a benefit apparent after only a few days of treatment. However, the effector mechanisms and dose–response relationships remain unclear. Therefore, we aim to discover the effector mechanisms of HBOT in UC patients and the dose–response relationships.

Deciphering the role of plasmacytoid dendritic cells in gut-associated lymphoid tissues during homeostasis and Crohn's Disease

Urs Mörbe  © Urs Mörbe

Background & aim of research

Inappropriate intestinal immune responses can result in Inflammatory Bowel Diseases (IBD), such as Crohn’s Disease (CD), that require lifelong treatment or surgery. While it is now well understood that T cells are a key driver of pathogenic intestinal immune responses during CD, the underlying molecular mechanisms and roles of other local immune cells remain incompletely understood. Interestingly, previous studies have shown that plasmacytoid dendritic cells (pDC) are potent modulators of immune cell responses and are enriched in the mucosa of IBD patients. However, their precise role remains unclear. This study aims to clarify the distribution and roles of pDC during health and CD.

Identification of markers to predict post-operative disease recurrence in Crohn's disease.

Annemarie de Vries © Annemarie de Vries

Alison Simmons © Alison Simmons

Background & aim of research

Ileocolonic resection (ICR) remains an important modality in the treatment of ileal or ileocolonic Crohn’s disease (CD)1,2. However, surgery is not curative and post-operative recurrence after ICR is common, with regard to clinical symptoms, endoscopy and need for re-resection2,3. To prevent post-operative recurrence, current guidelines advise to start prophylactic medication in patients at high risk4–6. Identification of these patients remains a challenge, despite clinical and histologic risk-stratification. The main aim of this study is to identify new biomarkers to predict endoscopic disease recurrence in a prospective cohort of CD patients who undergo ICR.

Early prediction of treatment response in children with Inflammatory Bowel Disease with intestinal ultrasound

Elsa van Wassenaer © Elsa van Wassenaer

Background & aim of research

Childhood-onset IBD is known for its more complicated disease course. Studies have established that achieving remission at an early stage of disease improves long-term prognosis. Therefore, choosing the right treatment for children with IBD in the early stages of disease is key to preventing disease progression and to altering the disease course. Intestinal ultrasound (IUS) is a promising non-invasive tool for IBD, but its potential for early prediction of treatment response has not yet been explored in the paediatric population. Therefore the aim of the RAINBOW-3 study is to evaluate, in children with IBD (new-onset or known), the predictive value of IUS at week 6 of treatment for treatment response at week 13.

The PTPN2 loss-of-function variant as predictor of therapeutic response to JAK inhibitor therapy in IBD

Marianne R. Spalinger © Marianne R. Spalinger

Raja Atreya © Raja Atreya

Background & aim of research

JAK inhibition has emerged as a promising novel therapeutic strategy in IBD. However, only a subgroup of patients responds to JAK inhibitors and there are currently no predictive markers available that predict sustained response. Our recent work strongly indicates that loss-of-function variants in the PTPN2 gene might serve as predictive markers for therapeutic effectiveness, and the main goal of this project is to define whether PTPN2 dysfunction can serve as a predictor for efficacious JAK inhibitor therapy.