Original Article

Subject Category: Microbe-microbe and microbe-host interactions

The ISME Journal (2008) 2, 716–727; doi:10.1038/ismej.2008.37; published online 10 April 2008

Molecular analysis of the gut microbiota of identical twins with Crohn's disease

Johan Dicksved1,7, Jonas Halfvarson2,7, Magnus Rosenquist1, Gunnar Järnerot2, Curt Tysk2,3, Juha Apajalahti4, Lars Engstrand5 and Janet K Jansson1,6

  1. 1Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden
  2. 2Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden
  3. 3School of Health and Medical Sciences, Örebro University, Örebro, Sweden
  4. 4Alimetrics Ltd, Helsinki, Finland
  5. 5Swedish Institute for Infectious Disease Control, Department of Bacteriology, Solna, Sweden
  6. 6Lawrence Berkeley National Laboratory, Division of Earth Sciences, Berkeley, CA, USA

Correspondence: JK Jansson, Lawrence Berkeley National Laboratory, Division of Earth Sciences, 1 Cyclotron Road, Berkeley, CA 94720, USA. E-mail: jrjansson@lbl.gov

7These authors contributed equally to this work.

Received 3 January 2008; Revised 13 March 2008; Accepted 14 March 2008; Published online 10 April 2008.

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Abstract

Increasing evidence suggests that a combination of host genetics and the composition of the gut microbiota are important for development of Crohn's disease (CD). Our aim was to study identical twins with CD to determine microbial factors independent of host genetics. Fecal samples were studied from 10 monozygotic twin pairs with CD (discordant n=6 and concordant n=4) and 8 healthy twin pairs. DNA was extracted, 16S rRNA genes were PCR amplified and T-RFLP fingerprints generated using general bacterial and Bacteroides group-specific primers. The microbial communities were also profiled based on their percentage G+C contents. Bacteroides 16S rRNA genes were cloned and sequenced from a subset of the samples. The bacterial diversity in each sample and similarity indices between samples were estimated based on the T-RFLP data using a combination of statistical approaches. Healthy individuals had a significantly higher bacterial diversity compared to individuals with CD. The fecal microbial communities were more similar between healthy twins than between twins with CD, especially when these were discordant for the disease. The microbial community profiles of individuals with ileal CD were significantly different from healthy individuals and those with colonic CD. Also, CD individuals had a lower relative abundance of B. uniformis and higher relative abundances of B. ovatus and B. vulgatus. Our results suggest that genetics and/or environmental exposure during childhood, in part, determine the gut microbial composition. However, CD is associated with dramatic changes in the gut microbiota and this was particularly evident for individuals with ileal CD.

Keywords:

Crohn's disease, terminal-restriction fragment length polymorphism (T-RFLP), discordant twins, concordant twins, Bacteroides