COmparison of MicroBiota AccordIng to Age in Crohn's Disease (COMeBACk)

Summary

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Description

The primary aim is to describe by principal component analysis and compare the gut microbiota between subgroups of paediatric-onset (n=75), elderly-onset CD patients (n=75) and control subjects (75 paediatric control and 75 elderly control subjects matched on age) without an a priori approach of hig...

The primary aim is to describe by principal component analysis and compare the gut microbiota between subgroups of paediatric-onset (n=75), elderly-onset CD patients (n=75) and control subjects (75 paediatric control and 75 elderly control subjects matched on age) without an a priori approach of high throughput sequencing of bacterial DNA. As it has been shown that the type of IBD-associated dysbiosis depends on ileal involvement, Paediatric-onset and elderly-onset CD patients will be stratified according this parameter. The secondary aims are: (I) Find specific bacteria involved in paediatric- and elderly-onset patients using PLS Discriminant Analysis (PLS-DA) that is a classical PLS regression (with a regression mode) but where the response variable is categorical. (II) Search for an association between bacterial dysbiosis and different genetic backgrounds in patients according to age at CD onset (paediatric-onset vs elderly-onset) and in control subjects; (III) Quantify of bacteria with invasive properties (E. coli, including adherent-invasive E.coli, Shigella, Salmonella, Yersinia, Campylobacter), and fecal fungal flora (Candida albicans, in particular) and their association with genetic and serological profiles according to age at CD onset and in control subjects; this study will include the comparison of the gut microbiome between subgroups of paediatric-onset, elderly-onset CD patients and control subjects. (IV) Study of environmental risk factors using a questionnaire to be submitted to CD patients and control subjects. The results would provide a better knowledge of the etiopathogenic ways in CD and would downstream open the way towards clinical trials focused on specific microbiota disorders according to age at CD onset. This project will help to decipher the potential involvement of specific bacteria in the physiopathology of CD. This could lead to the development of new therapeutic strategies either using optimized current treatments targeting bacteria. Data from clinical trials which for the great majority rarely include paediatric patients and set an upper limit for study eligibility at 65 years of age are thus focusing on adult-onset disease. Thus the potential specificities of paediatric- and elderly-onset diseases are not taken into account. A better knowledge of characteristics of CD at the extreme of life will be important to set up innovative clinical trials including specific therapeutics adapted to patients where disease occurred at the extreme age of life, especially as these patients did not benefited of specific trials. The ultimate goal is a better quality of care delivered to paediatric- and elderly-onset CD patients.

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