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.

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.

Ascertaining the role of the appendix in inflammatory bowel disease in a population-based cohort

Manasi Agrawal © Manasi Agrawal

Background & aim of research

Appendectomy at age <20 years for appendicitis or mesenteric lymphadenitis has been associated with a lower risk of Ulcerative Colitis (UC), but this association has not been detected when appendectomy is performed at an older age or for non-specific abdominal pain. Similar findings have been reported upon combining data from Swedish and Danish registers.  However, in a Danish cohort study of familial units, individuals who had first-degree relatives with appendicitis, but no personal history of appendicitis, at age <20 years also had a lower risk of UC. This risk was even lower in those with a family history of UC. 

Interventional studies on elective appendectomy for UC therapy are underway. The impact of appendiceal inflammation on UC outcomes, including cancer, are not well understood. 

The overall aim of this study is to understand the role of the appendix (appendicitis and appendectomy) in IBD risk and IBD outcomes. 

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.

Marc Ferrante © ECCO

Isabelle Cleynen © ECCO

Timothy Raine © ECCO

At the recent 18^th Congress of ECCO, Sebastian Zeissig (Dresden, Germany) stepped down as a member of the ECCO Scientific Committee. After two years of active membership, Sebastian became SciCom Chair back in 2020. Although this period was greatly affected by the pandemic, Sebastian made sure that ECCO continued to support clinical, translational and basic science. During his chairmanship, the different ECCO Fellowships, Grants and Travel Awards were streamlined and optimised. Together with the rest of the team, he spent a lot of energy in finding appropriate reviewers for the dozens of project proposals received every year. Sebastian was also the driving force behind the new ECCO Young Researcher Award, which was granted for the first time earlier this year. As SciCom Chair, he supervised two successful Scientific Workshops, one on precision medicine (together with Michael Scharl) and another on postoperative Crohn’s Disease recurrence (together with Yves Panis and Marc Ferrante). We thank Sebastian for his great enthusiasm, his perseverance and his friendship.

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.