Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease.
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.
Willing
Ben
B
Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Halfvarson
Jonas
J
Dicksved
Johan
J
Rosenquist
Magnus
M
Järnerot
Gunnar
G
Engstrand
Lars
L
Tysk
Curt
C
Jansson
Janet K
JK
D003106:Colon / Q000382:microbiology*; D003424:Crohn Disease / Q000235:genetics / Q000382:microbiology*; D004200:Diseases in Twins / Q000235:genetics / Q000382:microbiology*; D004926:Escherichia coli / Q000235:genetics / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000235:genetics / Q000382:microbiology; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000235:genetics / Q000382:microbiology; D006801:Humans; D007077:Ileal Diseases / Q000235:genetics / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D045857:Ruminococcus / Q000235:genetics / Q000302:isolation & purification; D014430:Twins, Monozygotic
D012336:RNA, Ribosomal, 16S