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.
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.
Authors: Patrick Veiga; Carey Ann Gallini; Chloé Beal; Monia Michaud; Mary L Delaney; Andrea DuBois; Artem Khlebnikov; Johan E T van Hylckama Vlieg; Shivesh Punit; Jonathan N Glickman; Andrew Onderdonk; Laurie H Glimcher; Wendy S Garrett Journal: Proc Natl Acad Sci U S A Date: 2010-10-04 Impact factor: 11.205
Authors: Nina Sanapareddy; Ryan M Legge; Biljana Jovov; Amber McCoy; Lauren Burcal; Felix Araujo-Perez; Thomas A Randall; Joseph Galanko; Andrew Benson; Robert S Sandler; John F Rawls; Zaid Abdo; Anthony A Fodor; Temitope O Keku Journal: ISME J Date: 2012-05-24 Impact factor: 10.302
Authors: Yvonne J Huang; Craig E Nelson; Eoin L Brodie; Todd Z Desantis; Marshall S Baek; Jane Liu; Tanja Woyke; Martin Allgaier; Jim Bristow; Jeanine P Wiener-Kronish; E Rand Sutherland; Tonya S King; Nikolina Icitovic; Richard J Martin; William J Calhoun; Mario Castro; Loren C Denlinger; Emily Dimango; Monica Kraft; Stephen P Peters; Stephen I Wasserman; Michael E Wechsler; Homer A Boushey; Susan V Lynch Journal: J Allergy Clin Immunol Date: 2010-12-30 Impact factor: 10.793
Authors: Páraic Ó Cuív; Daniel Aguirre de Cárcer; Michelle Jones; Eline S Klaassens; Daniel L Worthley; Vicki L J Whitehall; Seungha Kang; Christopher S McSweeney; Barbara A Leggett; Mark Morrison Journal: Microb Ecol Date: 2010-12-14 Impact factor: 4.552