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Re: Reduced microbial diversity in inflammatory bowel diseases (IBD)

Dear Editor,

Intestinal microbiota have become subject of intense investigation in inflammatory bowel disease (IBD) during the last years after some groups could demonstrate that significant alterations of the composition of enteric bacteria might be related to the underlying inflammatory process (1-5). However, the complexity of intestinal microbiota and the availability of a variety of different experimental approaches generated a patchwork of sometimes conflicting and inconsistent data. Manichanh et al. recently published an extensive study using metagenomic libraries, a novel molecular technique allowing the recruitment of full molecular information of complex microbial habitats (1). In metagenomic clone libraries with more than 25.000 clones that were generated from fecal samples of healthy subjects and active Crohn patients a significant loss of indigenous bacteria was found (1).

The article confirms our report that reduced bacterial diversity seems to be a hallmark of the biofilm in IBD 5. Using colonic biopsies we had found a loss of bacterial diversity of the mucosal microbiota in a large cohort of patients with IBD using different 16S rDNA-based detection techniques (5). Differently from the citation in the article of Manichanh et al., the taxa of the bacterial phylotypes were determined in our study by sequence homology analysis in clone libraries and not only by SSCP (5). The metagenomic approach used by Manichanh et al. is likely to be the most informative way of collecting microbial data of complex bacterial communities. Notably, this demonstrates that assessment of 16S rDNA based signals, especially when using large-scale clone libraries as in our paper, has sufficient power to determine bacterial richness and diversity. This is not too surprising because the taxonomical classification of metagenomic fragments is mainly based on 16S rDNA anchor genes.

In some aspects there are discrepancies between the different molecular studies. Manichanh et al. only demonstrate alterations of the fecal microbiota (1). As previously demonstrated, different compartments in the intestine contain complex ecological systems that are distinctly different (6). Therefore, the composition of bacterial consortia in the human feces, which contain a high number of transient bacteria, does not fully represent the mucosal microbiota (7, 8). Mucosa-related microbes (including intracellular microorganisms), however, seem to be a functionally relevant part of the intestinal microbiom directly interacting with the host immune system.

Generating and analyzing metagenome libraries is enormously expensive. Therefore, the number of patients that can be analysed will remain relatively small (1). The confirmation of a reduced bacterial diversity, however, could be now followed by a deep analysis of the functional capacities of the bacterial communities. These next steps would convert descriptive approaches into a mechanistic understanding. Manichanh et al. have introduced the metagenomic approach as a novel technique of collecting data from complex human biofilms.

Address all correspondence to:
Stefan Schreiber, M.D.
Institute for Clinical Molecular Biology
Christian-Albrechts-University Kiel
Schittenhelmstr. 12 24105 Kiel, Germany
Phone: +49 431 597 2350
Fax: +49 431 597 1842
E-mail: s.schreiber@mucosa.de

References

1. Manichanh C, Rigottier-Gois L, Bonnaud E, et al. Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut 2006;55:205-211.

2. Swidsinski A, Ladhoff A, Pernthaler A, et al. Mucosal Flora in Inflammatory Bowel Disease. Gastroenterology 2002;122:44-54.

3. Seksik P, Rigottier-Gois L, Gramet G, et al. Alterations of the dominant faecal bacterial groups in patients with Crohn's disease of the colon. Gut 2003;52:237-42.

4. Prindiville T, Cantrell M, Wilson K. Ribosomal DNA Sequence Analysis of Mucosa-Associated Bacteria in Crohn's Disease. Inflamm Bowel Dis 2004;10:824-33.

5. Ott SJ, Musfeldt M, Wenderoth DF, et al. Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease. Gut 2004;53:685-693.

6. Bignell DE, Oskarsson H, Anderson JM. Distribution and abundance of bacteria in the gut of a soil-feeding termite Procutiermes aburiensis (Termitidae, Termitinae). J Gen Microbiol 1980;117:393-403.

7. Zoetendal EG, von Wright A, Vilpponen-Salmela T, et al. Mucosa- associated bacteria in the human gastrointestinal tract are uniformly distributed along the colon and differ from the community recovered from feces. Appl Environ Microbiol 2002;68:3401-7.