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BIRD Young Investigator Grant 2024 - Winners

DEBORAH JANS (KU Leuven): Family matters: Investigating inflammatory bowel disease aggregation in multiplex families through DNA methylation profiling

Relatives of patients with inflammatory bowel disease (IBD) are at the highest risk of developing IBD. Some families exhibit a notably high prevalence of the disease, with three or more first-degree relatives affected. However, the reasons behind this high occurrence of IBD in these so-called multiplex families remain unclear. Families share genetics but also environmental factors. Epigenetic modifications, such as DNA methylation, are important mediators of gene-environment interactions.

We aim to deepen our understanding of familial IBD by investigating DNA methylation as a reflection of environmental influences in multiplex families.

Specifically, we will perform methylation profiling on peripheral blood samples of individuals of 60 multiplex families, each with a minimum of three affected first-degree relatives, and matched sporadic cases and controls. We will explore the differences in methylation patterns between (familial) cases and controls to look for associated genes, but also to match these differences to known exposure-related methylation signatures. The relative contribution of environment versus genetics might be different between sporadic and familial cases and therefore we will also compare methylation signals both quantitatively as qualitatively between sporadic and familial cases.

This project will provide further insights into the familial aggregation of IBD and how familial IBD cases differ from sporadic ones. Ultimately, understanding the underlying causes of familial aggregation will contribute to a clearer understanding of the pathogenesis of IBD as a whole.

 

CLÉMENCE VUCKOVIC (Hôpital Erasme): Longitudinal characterization of the gut and oral microbiota in Inflammatory Bowel Disease patients in remission and identification of predictive microbial factors of relapse” – ANTICIPATE

Inflammatory bowel diseases (IBD) are characterized by imbalanced host-local microbiota interactions. While gut microbiota changes are thought to be a trigger in disease activity and despite recent suggestions of oral dysbiosis as pejorative factor associated with disease activity, it has yet not been proven as a pivotal factor influencing disease relapses.

The aim of this research is to longitudinally characterize the oral and gut microbiota in IBD patients in remission and to assess whether their microbiota composition or metabolomic characteristics could predict disease relapse.

This single centre prospective cohort is based on highly selected IBD patients with strict definition of disease remission (n=200). All patients who remain in remission will be followed for 12 months. Patients who experience a flare during follow-up will be managed differently. The composition of the oral and gut microbiota will be determined by 16S rRNA and ITS2 gene sequencings, targeting bacteria and fungi, respectively. Metabolomic studies will be performed on saliva, serum and faeces samples using 1H-NMR with LC-MS as a complementary method. At the end of follow-up, we will examine changes in the microbiota and metabolite composition of patients prior to relapse.

 

SAEED ABDURAHIMAN (KU Leuven): Deciphering cellular dynamics and the role of microbiota in perianal Crohn's disease: a multiomics approach

Perianal fistulizing disease (PFD) is a debilitating complication of Crohn's disease (CD) that significantly impacts patients' quality of life, affecting their general well-being, social, professional, and sexual lives. This severe phenotype of CD is marked by the formation of fistulas and abscesses, highlighting an unmet need for more effective treatments. Despite advances in therapies, including biologics and small molecules, many patients still require invasive surgeries, underscoring the necessity for deeper understanding and improved therapeutic strategies for PFD.
 
This project aims to elucidate the biological mechanisms underlying PFD by focusing on its molecular and cellular dynamics and the interplay of host tisue and the microbiota. The research will investigate transcriptional changes in fistulas of CD patients compared to non-CD fistulas (CGF) and adjacent rectal tissues. It will also explore the spatial organization of cells within the fistula tissue, providing insights into the intercellular interactions critical to disease progression. Additionally, the project will examine the impact of the microbiota on these transcriptional changes through 16S rRNA sequencing, integrating these findings with transcriptional data to identify correlations between microbial changes and gene expression profiles.
 
By integrating these multidisciplinary approaches, this project seeks to provide a comprehensive understanding of the pathogenesis of PFD. This could potentially lead to the development of more effective treatments and therapeutic strategies for Crohn's disease, addressing a critical gap in current medical research and improving the lives of patients suffering from this challenging condition.