Fellowships & Grants Synopsis Reports

27April2023

ECCO Grant Study Synopsis: Sofía Frigerio

Sofía Frigerio, ECCO Grant Awardee

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.

Posted in ECCO News, SciCom, Committee News, Volume 18, Issue 1, Fellowships & Grants Synopsis Reports

27April2023

ECCO Grant Study Synopsis: Felix Grabherr

Felix Grabherr, ECCO Grant Awardee

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. 

Posted in ECCO News, SciCom, Committee News, Volume 18, Issue 1, Fellowships & Grants Synopsis Reports

27April2023

ECCO Grant Study Synopsis: Bahtiyar Yilmaz

Bahtiyar Yilmaz, ECCO Grant Awardee

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.

Posted in ECCO News, SciCom, Committee News, Volume 18, Issue 1, Fellowships & Grants Synopsis Reports

27April2023

ECCO Grant Study Synopsis: Laure Maes

Laure Maes, ECCO Grant Awardee

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.

Posted in ECCO News, SciCom, Committee News, Volume 18, Issue 1, Fellowships & Grants Synopsis Reports

27April2023

ECCO Grant Study Synopsis: Manasi Agrawal

Manasi Agrawal, ECCO Grant Awardee

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. 

Posted in ECCO News, SciCom, Committee News, Volume 18, Issue 1, Fellowships & Grants Synopsis Reports

27April2023

ECCO Grant Study Synopsis: Joana Gaifem

Joana Gaifem, ECCO Grant Awardee

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.

Posted in ECCO News, SciCom, Committee News, Volume 18, Issue 1, Fellowships & Grants Synopsis Reports

27April2023

ECCO Grant Study Synopsis: Francesco Strati

Francesco Strati, ECCO Grant Awardee

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.

Posted in ECCO News, SciCom, Committee News, Volume 18, Issue 1, Fellowships & Grants Synopsis Reports

27April2023

ECCO Grant Study Synopsis: Nicolas Pierre

Nicolas Pierre, ECCO Grant Awardee

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.

Posted in ECCO News, SciCom, Committee News, Volume 18, Issue 1, Fellowships & Grants Synopsis Reports

27April2023

D-ECCO Grant Study Synopsis: Meropi Kontogianni

Meropi Kontogianni, D-ECCO Grant Awardee

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.

Posted in ECCO News, SciCom, Committee News, Volume 18, Issue 1, Fellowships & Grants Synopsis Reports

27April2023

N-ECCO Grant Study Synopsis: Zahira Pérez

Zahira Pérez , N-ECCO Grant Awardee

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.

Posted in ECCO News, SciCom, Committee News, Volume 18, Issue 1, Fellowships & Grants Synopsis Reports