Unravelling the microbiome in paediatric Crohn’s disease: A journey towards personalised therapy
Crohn’s Disease (CD) is a type of inflammatory bowel disease and is characterised by chronic inflammation of the gastrointestinal tract, with symptoms occurring in a relapsing and remitting form. Childhood-onset CD presents with more extensive intestinal involvement compared to adult-onset disease. In addition, disease-onset during childhood or adolescence impairs emotional and pubertal development and subsequently impacts mental health and quality of life. Therefore, there is a high for more understanding of the disease to ensure more effective and safe treatment strategies for induction and maintenance of remission for a longer period of time. The exact pathophysiology of CD is still unknown, but the microbiome is suspected to play a key role in mediating genetic, immunologic and environmental factors contributing to disease development. In part 1 , we therefore aimed to unravel the role of the microbiome and metabolome in paediatric CD. We found differences between healthy children and those with CD, but also observed that the microbiome and metabolome of children with CD becomes more similar to that of healthy children during successful (nutritional) treatment. In part 2 we explored the possibilities of the microbiome as a biomarker in paediatric CD. We developed a community-based model aiming to predict the course of the disease in the first year after diagnosis based on baseline microbiome results only with high accuracy. Finally, we applied this model in a pilot clinical study with the aim of providing personalised treatment with antibiotics to children with a high-risk microbiome (associated with a more complicated disease course) in addition to standard therapy. With this, we took the first steps towards much needed personalised therapeutic strategies in the future.
https://pure.uva.nl/ws/files/127172977/cover.jpg
https://pure.uva.nl/ws/files/127172979/Front_matter.pdf
https://pure.uva.nl/ws/files/127173563/Chapter_1.pdf
https://pure.uva.nl/ws/files/127173565/Chapter_2.pdf
https://pure.uva.nl/ws/files/127173567/Chapter_3.pdf
https://pure.uva.nl/ws/files/127173569/Chapter_4.pdf
https://pure.uva.nl/ws/files/127173571/Chapter_5.pdf
https://pure.uva.nl/ws/files/127173573/Chapter_6.pdf
https://pure.uva.nl/ws/files/127173577/Chapter_8.pdf
https://pure.uva.nl/ws/files/127173579/Chapter_9.pdf
https://pure.uva.nl/ws/files/127173581/Thesis_summary_General_discussion_Nederlandse_samenvatting.pdf
https://pure.uva.nl/ws/files/127173583/Appendix.pdf
https://dare.uva.nl/personal/pure/en/publications/unravelling-the-microbiome-in-paediatric-crohns-disease