Feeding immunity: development of a novel glycan-based dietary strategy for IBD prevention

Joana Gaifem © Joana Gaifem

Background & aim of research

Dietary interventions have been shown to ameliorate symptoms in patients with mild or moderate IBD. Nevertheless, these therapies are only effective for a subset of patients, raising the need for novel dietary intervention strategies that aim to prevent IBD development. Glycosylation is a major post-translational mechanism characterised by the addition of carbohydrate structures, called glycans, to essentially all cells. We have revealed that mucosal T cells from Ulcerative Colitis patients exhibit alterations in mucosal glycosylation, which positively correlate with T cell hyperactivity and disease severity. We have also demonstrated that mice deficient in branched N-glycosylation display increased susceptibility to severe colitis. Supplementation of these mice with glycans resulted in disease control via inhibition of Th1/Th17 immune responses.

In this research we aim to explore whether dietary supplementation with glycans promotes a superior function for nutraceutical intervention to promote IBD prevention, characterising the effect of mucosal glycosylation reprogramming in shaping the intestinal environment.

iNKT cells immunomodulation and mucosal healing by microbiota-derived lactate (OCELOT)

Francesco Strati © Francesco Strati

Background & aim of research

Invariant natural killer T (iNKT) cells are unconventional T lymphocytes that play a critical role in mucosal immunity. Although iNKT cells sense the microbiota of IBD patients, promoting pro-inflammatory responses, their rapid responsiveness to the intestinal microenvironment can be harnessed to promote immunoregulatory rather than pro-inflammatory responses. OCELOT’s central hypothesis is that iNKT cells are the primary immune cells that sense microbiota-derived metabolic signals promoting the resolution of inflammation. In particular, OCELOT argues that microbiota-derived lactate can tightly control iNKT cell function, promoting mucosal tolerance while preventing T cell-mediated inflammation and tissue injury.

Development of biomarker signatures as an alternative to endoscopy: looking beyond inflammation

Nicolas Pierre © Nicolas Pierre

Background & aim of research

In Crohn’s Disease (CD), the treat-to-target strategy has become the standard of care [1, 2]. This clinical concept consists in escalating/optimising the treatment (e.g. dose, frequency, type of drugs) until a state of remission (target) is achieved. Overall, treatment targets evolve towards a deeper level of remission and it is in this context that endoscopic remission has become a primary objective. However, endoscopy remains invasive and costly, is not well accepted by patients and does not allow tight control of disease activity. Thus, attention is turning to non-invasive biomarkers that can replace endoscopy. Our group recently made progress in monitoring disease activity with blood proteins. More precisely, we found distinct biological profiles to be associated with the risk of short-term and mid/long-term relapse in CD patients who stop infliximab [3–5]. By measuring 161 blood proteins, we captured a more complete picture of the disease activity than is achieved with classic inflammatory markers. Clearly, looking beyond inflammation is necessary in order to monitor disease activity more effectively. Based on our previous work, we aim to develop biomarker signatures as an alternative to endoscopy.

Combination treatment with partial enteral nutrition and biologics as induction therapy for adults with active ileocolonic Crohn’s Disease: a pilot study

Meropi Kontogianni © Meropi Kontogianni

Background & aim of research

There is strong interest in investigating combination therapies for active Crohn’s Disease (CD) to improve response to biologics and to mitigate secondary loss of response, without increasing the risk of drug-associated side effects. Exclusive enteral nutrition is an established treatment for active CD, but tolerance is poor. In partial enteral nutrition (PEN) only part of the habitual diet is replaced by the proprietary formula, allowing patients to eat some normal food. PEN at high volume (>50% energy requirements) can prolong remission compared to unrestricted diet. Therefore, the aim of the present study is to compare clinical remission/response rates to standard treatment with adalimumab (ADA) between a group of CD patients on unrestricted diet and another group on 50% PEN. Secondary aims are to explore how these two treatments change the gut microbiome composition and its diet-related function.

Assessment of desire and sexual function in Inflammatory Bowel Disease patients: a cross-sectional study with matched controls

Zahira Pérez  © Zahira Pérez

Background & aim of research

Sexual dysfunction (SD) rates are higher in the Inflammatory Bowel Disease (IBD) patient population compared with the general population. Overall among IBD patients, low sexual desire and greater difficulty in achieving orgasms are the most frequently reported sexual problems. In addition, women report worse body image and lower sexual desire. Being diagnosed with major depression, undergoing surgery or suffering IBD symptoms are the usual triggers.

Despite the importance of sexual well-being, there is a lack of research focusing on sexual desire in IBD patients. This study aims to assess the prevalence of sexual dysfunction and to analyse sexual desire from a dual viewpoint: a dyadic and a solitary perspective. The intention is to describe sexual function and its possible correlations with the presence of anxiety and depression, disease activity and quality of life.

Recognizing the prevalence of sexual dysfunction in IBD patients can improve clinical practice and optimize resource planning for sexual healthcare. Early diagnosis and primary prevention can help address sexuality-related concerns in this population.

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.