Transversal multicentric French study on the microbiota in patients with Crohn's disease and their first degree healthy relatives The primary objective is the comparison of microbiota between patients with CD, healthy controls non genetically linked and first degree healthy relatives of patients with CD.
Crohn's disease is a chronic inflammatory bowel disease associating flares and remission periods. Its etiology is unknown and there are no specific therapy. CD affects young patients and has a major impact on quality of life. There are few population-based studies and there are about 2.5 million affected patients in Europe and North America. From data from EPIMAD Registry the number of affected patients in France should be 200 000. The Crohn's disease pathogenesis is bad known; It coul be the results of the activation of the gastro-intestinal immune system toward gut microbiota in genetically susceptible hosts. In CD patients there is an important ecologic modification of the flora with an excess of Bacteroidetes and Proteobacteria and a decrease of anti inflammatory bacteria (Firmicutes). In ileum of CD patients a specific E Coli (adherent and invasive E Colo) is found in two thirds of cases.The presence of this AIEC seems to be associated to the variant NOD2 (results from our team in multiplex families). In a family with at least 1 patient with CD, the healthy first degree relatives present a high risk (\* 10) to also develop a CD. The primary objective is the comparison of microbiota between patients with CD, healthy controls non genetically linked and first degree healthy relatives of patients with CD. The first endpoint is the Lachnospiraceae rates in each group. The secondary objectives are : 1. the search for an association between bacterial dysbiosis and different genetic backgrounds in patients with CD, their first degree healthy relatives and controls. 2. the quantification of potential invasive 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 in patients with CD, their healthy relatives and control subjects. 3. a study of environmental risk factors using a questionnaire to be submitted to CD patients, their healthy relatives and control subjects.
Study Type
OBSERVATIONAL
Enrollment
240
fecal microbiota analysis antibodies in serum and saliva DNA polymorphisms
Amiens University & Hospital
Amiens, France
cLERMONT fERRAND University Hospital
Clermont-Ferrand, France
APHP Kremlin Bicêtre
Le Kremlin-Bicêtre, France
CHRU,Hôpital Jeanne de Flandres
Lille, France
Percentage of Lachnospiraceae bacteria in stools within 3 groups
After extraction DNA, microbiota will be studied via study of ribosomal DNA 16S using quantitative PCR and pyroséquençage
Time frame: 1 YEAR
Number of bacteria Firmicutes phylum (including Faecalibacterium prausnitzii and Clostridium Leptum) in stools within 3 groups
After extraction DNA, microbiota will be studied via study of ribosomal DNA 16S using quantitative PCR and pyroséquençage
Time frame: 1 year
Define different genetic and serologic backgrounds within 3 groups
Genetic analysis will include 380 genetic variants génétiques that will be genotyped including classic variants involved in CD: variants or mutations of NOD2, NOD1, IL23R, ATG16L1, DGL5, TNF, IL6, NFKB1... genes. Serological analysis will included anti-OmpC, anti-I2 and ASCA auto antibodies.
Time frame: 1 year
Quantify of bacteria with invasive properties (including AIEC) within 3 groups
Amplify bacterial DNA of Salmonella Typhi (amplification of ITS area specific of ARNr 16S-23S gene. For AIEC, using of qPCR methods based on chuA and yjaA genes.
Time frame: 1 year
Study of environmental risk factors within 3 groups
Specific questionnaire on environmental risk factors including vaccination, antibiotic use, ionfections, Home facilities and Diet befor the CD diagnosis
Time frame: 1 year
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Hôpital Claude Huriez, CHRU
Lille, France
Nancy University Hospital
Nancy, France
Aphp Necker
Paris, France
APHP Robert Debré
Paris, France
Aphp St Antoine
Paris, France
Rouen University Hospital
Rouen, France