Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn's disease and their unaffected siblings.

Autor:	Hedin CR; Diabetes and Nutritional Sciences Division, School of Medicine, King's College London, London, UK Centre for Digestive Diseases, Blizard Institute, Queen Mary University of London, London, UK., McCarthy NE; Centre for Digestive Diseases, Blizard Institute, Queen Mary University of London, London, UK., Louis P; Microbiology Group, Gut Health Theme, Rowett Institute of Nutrition and Health, University of Aberdeen, Bucksburn, Aberdeen, UK., Farquharson FM; Microbiology Group, Gut Health Theme, Rowett Institute of Nutrition and Health, University of Aberdeen, Bucksburn, Aberdeen, UK., McCartney S; Department for Gastroenterology and Clinical Nutrition, University College Hospitals NHS Foundation Trust, London, UK., Taylor K; Department of Medical and Molecular Genetics, King's College London, London, UK., Prescott NJ; Department of Medical and Molecular Genetics, King's College London, London, UK., Murrells T; National Nursing Research Unit, Florence Nightingale School of Nursing and Midwifery, King's College London, London, UK., Stagg AJ; Centre for Immunology and Infectious Disease, Blizard Institute, Queen Mary University of London, London, UK., Whelan K; Diabetes and Nutritional Sciences Division, School of Medicine, King's College London, London, UK., Lindsay JO; Centre for Digestive Diseases, Blizard Institute, Queen Mary University of London, London, UK Gastroenterology Division, Barts Health NHS Trust, London, UK.
Jazyk:	angličtina
Zdroj:	Gut [Gut] 2014 Oct; Vol. 63 (10), pp. 1578-86. Date of Electronic Publication: 2014 Jan 07.
DOI:	10.1136/gutjnl-2013-306226
Abstrakt:	Objective: Crohn's disease (CD) is associated with intestinal dysbiosis, altered blood T cell populations, elevated faecal calprotectin (FC) and increased intestinal permeability (IP). CD-associated features present in siblings (increased risk of CD) but not in healthy controls, provide insight into early CD pathogenesis. We aimed to (1) Delineate the genetic, immune and microbiological profile of patients with CD, their siblings and controls and (2) Determine which factors discriminate between groups. Design: Faecal microbiology was analysed by quantitative PCR targeting 16S ribosomal RNA, FC by ELISA, blood T cell phenotype by flow cytometry and IP by differential lactulose-rhamnose absorption in 22 patients with inactive CD, 21 of their healthy siblings and 25 controls. Subject's genotype relative risk was determined by Illumina Immuno BeadChip. Results: Strikingly, siblings shared aspects of intestinal dysbiosis with patients with CD (lower concentrations of Faecalibacterium prausnitzii (p=0.048), Clostridia cluster IV (p=0.003) and Roseburia spp. (p=0.09) compared with controls). As in CD, siblings demonstrated a predominance of memory T cells (p=0.002) and elevated naïve CD4 T cell β7 integrin expression (p=0.01) compared with controls. FC was elevated (>50 μg/g) in 8/21 (38%) siblings compared with 2/25 (8%) controls (p=0.028); whereas IP did not differ between siblings and controls. Discriminant function analysis determined that combinations of these factors significantly discriminated between groups (χ(2)=80.4, df=20, p<0.001). Siblings were separated from controls by immunological and microbiological variables. Conclusions: Healthy siblings of patients with CD manifest immune and microbiological abnormalities associated with CD distinct from their genotype-related risk and provide an excellent model in which to investigate early CD pathogenesis. (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
Databáze:	MEDLINE
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