Fellowships & Grants Synopsis Reports

15December2020

ECCO Grant Study Synopsis: Silke Kiessling

Silke Kiessling, ECCO Grant Awardee

Induction of circadian microbial function in chronic intestinal inflammation

Silke Kiessling
© Silke Kiessling

Aim of research

The body clock regulates behaviour and physiology in a circadian (24-h) manner. Circadian disruption, as occurs in shift workers, is associated with gastrointestinal (GI) pathologies, including Inflammatory Bowel Disease (IBD).                              

The intestinal epithelial cells, key regulators of barrier function and immune homeostasis, harbour a clock which may play a major role in maintaining intestinal homeostasis. In addition, the majority of the gut microbiome, including microbial metabolites, show circadian rhythmicity in both mice and humans. It remains to be addressed whether changes in microbial composition and function are regulated by the intestinal clock and influence GI diseases. Thus, we aim to test whether (i) arrhythmic microbial composition and function in IBD is caused by intestinal clock dysfunction, (ii) lost rhythmicity in microbial metabolites promotes IBD and (iii) IBD pathogenesis can be modulated by restoring circadian microbial metabolite production.

Posted in ECCO News, Committee News, SciCom, Fellowships & Grants Synopsis Reports, Volume 15, Issue 4

15December2020

ECCO Grant Study Synopsis: Chloe E. Huseyin

Chloe E. Huseyin, ECCO Grant Awardee

The gut mycobiome in Inflammatory Bowel Disease: addressing ITS confounders

Chloe E. Huseyin
© Chloe E. Huseyin

Aim of research

The gut mycobiome refers to the community of fungi present in the human gastrointestinal tract. Surveys of the mycobiome are considerably underrepresented in the literature compared to surveys of bacteria; however, this does not imply that the mycobiome is of lesser importance. Indeed, fungi are invasive opportunistic pathogens and the human gut an internal reservoir.
Much can be learned from the abundant bacterial literature utilising next generation sequencing (NGS) technology. An ever-increasing number of exogenous and endogenous confounding factors have too often been discovered retrospectively. This both influences and complicates the ability to discern meaningful conclusions within and across studies, ultimately not only costing time and resources but also increasing research fatigue.
Several mycobiome studies have postulated that the same confounding effects are relevant to the mycobiome, especially host diet, which is complicated by the consumption of fungi used in the food and beverage industry.

The main aims of this research are to:

  1. Assess the inherent effects of several methodological choices, and
  2. Investigate potential confounders of importance with respect to Inflammatory Bowel Disease (IBD) mycobiome research.

Posted in ECCO News, Committee News, SciCom, Fellowships & Grants Synopsis Reports, Volume 15, Issue 4

15December2020

ECCO Grant Study Synopsis: Krisztina Gecse

Krisztina Gecse, ECCO Grant Awardee

STRICTuring Crohn’s disease assessment using advanced Ultrasound and magnetic REsonance imaging techniques for evaluation of inflammation and fibrosis (STRICTURE)

Krisztina Gecse
© Krisztina Gecse

Aim of research

Patients with Crohn’s Disease present predominantly with inflammation; however, a significant proportion of patients already exhibit strictures at diagnosis or develop fibrostenotic complications during their disease course. Whereas predominantly inflammatory strictures are likely to benefit from medical therapy, predominantly fibrotic strictures often require a surgical approach. As strictures are rarely identified merely as fibrotic or inflammatory, identifying the predominant component of the stricture is necessary to guide clinical decision making. However, currently used imaging modalities are unable to adequately determine stricture composition.

Intestinal ultrasound (IUS) and MRI are both frequently used in the evaluation of disease activity in CD. Previous studies have shown that advanced modalities of both techniques are promising for the characterisation of stricture composition. However, data are scarce and most studies have not combined MRI and IUS parameters.

Therefore, the aim of the STRICTURE study is to evaluate the use of state-of-the-art cross-sectional imaging parameters to identify stricture composition, as defined by the histopathological degree of inflammation and fibrosis in the surgical resection specimen.

Posted in ECCO News, Committee News, SciCom, Fellowships & Grants Synopsis Reports, Volume 15, Issue 4

15December2020

ECCO Grant Study Synopsis: Gabriele Dragoni

Gabriele Dragoni, ECCO Grant Awardee

Role of PADI4 in Crohn's disease: the citrullination of proteins in the transition from inflammation to fibrosis

Gabriele Dragoni
© Gabriele Dragoni

Aim of research

Citrullination is a post-translational modification of proteins, mediated by enzymes called PADs (peptidylarginine deiminases). PAD4 has recently been shown to citrullinate histone 3 (H3cit) in the nucleus, leading to the expulsion of extracellular traps from neutrophils (NETs), whose presence in Crohn’s Disease (CD) is debated.

The aim of this project is to investigate the role of PAD4 in inflammatory and fibrotic contexts of ileal CD.

Posted in ECCO News, Committee News, SciCom, Fellowships & Grants Synopsis Reports, Volume 15, Issue 4

15December2020

ECCO Grant Study Synopsis: Neil Chanchlani

Neil Chanchlani, ECCO Grant Awardee

Understanding the mechanisms of anti-TNF treatment failure in patients with Crohn’s Disease: a proteomic analysis of the PANTS cohort

Neil Chanchlani
© Neil Chanchlani

Aim of research

In the Personalised Anti-TNF Therapy in Crohn’s Disease (PANTS) prospective cohort study, we followed 1,610 patients with Crohn’s Disease treated with infliximab or adalimumab for three years. About one in four patients experienced primary non-response and one-third of initial responders lost response, leaving only one-third in remission at one year.  

 

A limited number of proteomic markers have been implicated in anti-TNF treatment failure, but their relative effects and interactions have not been fully explored. We aim:

  1. To identify novel protein biomarkers linked to intestinal inflammation and immunity that influence pharmacokinetic or pharmacodynamic related primary non-response and non-remission at one year, using two multiplex Olink proteomic panels.
  2. Validate previously postulated protein markers associated with anti-TNF primary non-response and non-remission at one year, including TREM-1, oncostatin M, Vitamin D, ASCA, ANCA and anti-OmpC.

Posted in ECCO News, Committee News, SciCom, Fellowships & Grants Synopsis Reports, Volume 15, Issue 4

15December2020

ECCO Grant Study Synopsis: Simona Bertoni

Simona Bertoni, ECCO Grant Awardee

CCR6 blockade as novel therapeutic strategy against inflammatory bowel disease

Simona Bertoni
© Simona Bertoni

Aim of research

CCL20 and its cognate receptor CCR6 are dysregulated in the colonic mucosa and serum of IBD patients; their genes have been identified as susceptibility genes for IBD and an anti-CCL20 neutralizing antibody has been reported to be beneficial in TNBS-induced colitis.
Our working hypothesis is that blocking the CCL20-CCR6 axis represents a novel and promising approach to IBD therapy by limiting neutrophil recruitment to the inflamed tissues and by restoring the balance of effector/regulatory T cells.
Accordingly, our aim is the preclinical validation of small-molecule CCR6 antagonists as potential drug candidates for the treatment of IBD.

Posted in ECCO News, Committee News, SciCom, Fellowships & Grants Synopsis Reports, Volume 15, Issue 4

15December2020

ECCO Grant Study Synopsis: Marieke Barnhoorn

Marieke Barnhoorn, ECCO Grant Awardee

Unraveling the immunoregulatory effects of local mesenchymal stromal cell therapy in patients with IBD

Marieke Barnhoorn
© Marieke Barnhoorn

Aim of research

Local mesenchymal stromal cell (MSC) therapy is approved for the treatment of Crohn’s Disease-associated perianal fistulas. However, little is known about the mechanism(s) of action of local MSC therapy. In this project we intend to unravel the engraftment and immunoregulatory effects of local MSC therapy in patients with refractory IBD.

Posted in ECCO News, Committee News, SciCom, Fellowships & Grants Synopsis Reports, Volume 15, Issue 4

30September2020

ECCO Fellowship Study Synopsis: Ferdinando D'Amico

Ferdinando D'Amico, ECCO Fellowship Awardee

Comparative accuracy of the standard Lémann index versus the simplified Lémann index for Crohn’s Disease: a prospective observational cohort study

Ferdinando D'Amico
© Ferdinando D'Amico

Aim of research

Crohn's Disease (CD) is an idiopathic Inflammatory Bowel Disease (IBD) characterised by transmural inflammation of the affected tracts. The uncontrolled inflammation can lead to bowel damage, defined as the onset of strictures, abscesses or fistulas negatively impacting patients' quality of life and outcomes. The Lémann index (LI) is a recently validated tool that was specifically designed to assess the presence of penetrating or stenosing lesions and to quantify their severity. LI is a complex and time-consuming score which is based on imaging [magnetic resonance imaging (MRI)] and endoscopic procedures. Of note, it is mainly used in clinical trials, while its use in clinical practice is limited. Our aim was to develop a simplified LI and to compare the correlation between this simplified LI and the standard LI in assessing bowel damage.

Posted in ECCO News, Committee News, SciCom, Fellowships & Grants Synopsis Reports, Volume 15, Issue 3

30September2020

ECCO Fellowship Study Synopsis: Andres Machicote

Andres Machicote, ECCO Fellowship Awardee

Targeting CD4+ T-cell plasticity in Inflammatory Bowel Diseases

Andres Machicote
© Andres Machicote

Aim of research

Inflammatory Bowel Diseases (IBD) are devastating diseases induced by a breakdown of gut homeostasis, in which CD4+ effector T cells are major mediators of the inflammatory response. Interestingly, CD4+ effector T cells can convert into regulatory T cells, thereby controlling inflammation. However, the forces driving this T-cell plasticity remain largely unexplored, especially in IBD patients. In this regard, changes in the microbiota that can induce different T-cell profiles are commonly observed during IBD. The present proposal aims to elucidate how CD4+ T-cell plasticity can be modulated from a pro-inflammatory towards an anti-inflammatory profile in IBD patients. Our hypothesis is that the microbiota may modulate T cells towards an anti- or pro-inflammatory profile. To address this issue, we aim to analyse T-cell plasticity in IBD patients and mouse IBD models, and to correlate our findings with the microbiota composition. Furthermore, we will study whether antibiotics commonly used to treat IBD affect T-cell plasticity through microbiota-dependent processes.

Posted in ECCO News, Committee News, SciCom, Fellowships & Grants Synopsis Reports, Volume 15, Issue 3

17December2019

ECCO Grant Study Synopsis: Gordon Moran

Gordon Moran, ECCO Grant Awardee

Stopping Aminosalicylate Therapy in Inactive Crohn’s Disease (STATIC) study: a randomized, open-label, non-inferiority trial

Gordon Moran
© 
Gordon Moran

Aim of research

Oral 5-ASA agents have proven effective for inducing and maintaining remission in mild-to-moderate Ulcerative Colitis (UC) and thus are commonly used as first-line agents. However, in contrast to UC, there is uncertainty regarding their effectiveness in Crohn’s Disease (CD). For induction of remission in CD, a Cochrane review of randomised controlled trials (RCTs) and meta-analysis found no evidence that low/high dose 5-ASA was superior to placebo. Several studies originating from North America and Europe indicate that 5-ASA agents are the most commonly prescribed drug class for patients with CD. Therefore, there is discordance between clinical prescribing practice and evidence from RCTs.

Posted in ECCO News, Committee News, SciCom, Fellowships & Grants Synopsis Reports, Volume 14, Issue 4