Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease

Authors

  • Ben Willing PhD,

    1. Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden
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    • The first 2 authors contributed equally to this work.

  • Jonas Halfvarson MD PhD,

    1. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden
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    • The first 2 authors contributed equally to this work.

  • Johan Dicksved PhD,

    1. Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden
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  • Magnus Rosenquist PhD,

    1. Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden
    2. Department of Oncology, Radiology and Clinical Immunology, Uppsala University Hospital, Uppsala, Sweden
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  • Gunnar Järnerot MD PhD,

    1. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden
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  • Lars Engstrand MD PhD,

    1. Department of Bacteriology, Swedish Institute for Infectious Disease Control, Solna, Sweden
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  • Curt Tysk MD PhD,

    1. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden
    2. School of Health and Medical Sciences, Örebro University, Örebro, Sweden
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  • Janet K. Jansson PhD

    Corresponding author
    1. Lawrence Berkeley National Laboratory, Division of Earth Sciences, Berkeley, California
    • Lawrence Berkeley National Laboratory, Earth Science Division, 1 Cyclotron Rd., MS 70A-3317D, Berkeley, CA 94720
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Abstract

Background: Large interindividual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease (CD).

Methods: To reduce variations in exposure during establishment of the gut flora and the influence of genotype, we studied the mucosa-associated microbiota of monozygotic twin pairs that were discordant (n = 6) or concordant (n = 4) for CD. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing, and quantitative real-time polymerase chain reaction (PCR).

Results: The microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal CD had a dramatically lower abundance (P < 0.001) of Faecalibacterium prausnitzii and increased abundance (P < 0.03) of Escherichia coli compared to healthy co-twins and those with CD localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype.

Conclusions: The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal CD phenotype, distinct from colonic CD, and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of CD and eventually customized treatment.

(Inflamm Bowel Dis 2009)

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