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Contributed by Norman R. Pace, July 16, 2007 (received for review June 7, 2007)
Abstract
The two primary human inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are idiopathic relapsing disorders characterized by chronic inflammation of the intestinal tract. Although several lines of reasoning suggest that gastrointestinal (GI) microbes influence inflammatory bowel disease (IBD) pathogenesis, the types of microbes involved have not been adequately described. Here we report the results of a culture-independent rRNA sequence analysis of GI tissue samples obtained from CD and UC patients, as well as non-IBD controls. Specimens were obtained through surgery from a variety of intestinal sites and included both pathologically normal and abnormal states. Our results provide comprehensive molecular-based analysis of the microbiota of the human small intestine. Comparison of clone libraries reveals statistically significant differences between the microbiotas of CD and UC patients and those of non-IBD controls. Significantly, our results indicate that a subset of CD and UC samples contained abnormal GI microbiotas, characterized by depletion of commensal bacteria, notably members of the phyla Firmicutes and Bacteroidetes. Patient stratification by GI microbiota provides further evidence that CD represents a spectrum of disease states and suggests that treatment of some forms of IBD may be facilitated by redress of the detected microbiological imbalances.
Footnotes
- ¶To whom correspondence should be addressed. E-mail: norman.pace{at}colorado.edu
-
Author contributions: D.N.F., E.C.B., N.H., and N.R.P. designed research; D.N.F., A.L.S.A., R.A.F., and N.H. performed research; D.N.F. contributed new reagents/analytic tools; D.N.F., E.C.B., N.H., and N.R.P. analyzed data; and D.N.F. and N.R.P. wrote the paper.
-
The authors declare no conflict of interest.
-
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. EF695452–EF710623).
-
This article contains supporting information online at www.pnas.org/cgi/content/full/0706625104/DC1.
- Abbreviations:
- IBD,
- inflammatory bowel disease;
- CD,
- Crohn's disease;
- UC,
- ulcerative colitis;
- SSU rRNA,
- small subunit rRNA;
- OTU,
- operational taxonomic unit;
- MAP,
- Mycobacterium avium spp. Paratuberculosis;
- PCA,
- principal components analysis;
- Q-PCR,
- quantitative PCR.
- © 2007 by The National Academy of Sciences of the USA
- Daniel N. Frank *,
- Allison L. St. Amand *,
- Robert A. Feldman †,
- Edgar C. Boedeker ‡,
- Noam Harpaz §, and
- Norman R. Pace * , ¶
- *Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347;
- †SymBio Corporation, Menlo Park, CA 94025;
- ‡Department of Medicine, University of New Mexico, Albuquerque, NM 87131; and
- §Department of Pathology, Mount Sinai School of Medicine, New York, NY 10029
-
Contributed by Norman R. Pace, July 16, 2007 (received for review June 7, 2007)
Abstract
The two primary human inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are idiopathic relapsing disorders characterized by chronic inflammation of the intestinal tract. Although several lines of reasoning suggest that gastrointestinal (GI) microbes influence inflammatory bowel disease (IBD) pathogenesis, the types of microbes involved have not been adequately described. Here we report the results of a culture-independent rRNA sequence analysis of GI tissue samples obtained from CD and UC patients, as well as non-IBD controls. Specimens were obtained through surgery from a variety of intestinal sites and included both pathologically normal and abnormal states. Our results provide comprehensive molecular-based analysis of the microbiota of the human small intestine. Comparison of clone libraries reveals statistically significant differences between the microbiotas of CD and UC patients and those of non-IBD controls. Significantly, our results indicate that a subset of CD and UC samples contained abnormal GI microbiotas, characterized by depletion of commensal bacteria, notably members of the phyla Firmicutes and Bacteroidetes. Patient stratification by GI microbiota provides further evidence that CD represents a spectrum of disease states and suggests that treatment of some forms of IBD may be facilitated by redress of the detected microbiological imbalances.
- Crohn's disease
- culture-independent microbiology
- ulcerative colitis
- rRNA
Footnotes
- ¶To whom correspondence should be addressed. E-mail: norman.pace{at}colorado.edu
-
Author contributions: D.N.F., E.C.B., N.H., and N.R.P. designed research; D.N.F., A.L.S.A., R.A.F., and N.H. performed research; D.N.F. contributed new reagents/analytic tools; D.N.F., E.C.B., N.H., and N.R.P. analyzed data; and D.N.F. and N.R.P. wrote the paper.
-
The authors declare no conflict of interest.
-
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. EF695452–EF710623).
-
This article contains supporting information online at www.pnas.org/cgi/content/full/0706625104/DC1.
- Abbreviations:
- IBD,
- inflammatory bowel disease;
- CD,
- Crohn's disease;
- UC,
- ulcerative colitis;
- SSU rRNA,
- small subunit rRNA;
- OTU,
- operational taxonomic unit;
- MAP,
- Mycobacterium avium spp. Paratuberculosis;
- PCA,
- principal components analysis;
- Q-PCR,
- quantitative PCR.
- © 2007 by The National Academy of Sciences of the USA
Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases
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