Reduced microbial diversity in inflammatory bowel diseases

Intestinal microbiota have become the subject of intense investigation in inflammatory bowel disease (IBD) over the past years after some groups demonstrated that significant alterations of the composition of enteric bacteria might be related to the underlying inflammatory process (Gut 2006;55:205–11).¹,²,³,⁴ However, the complexity of the intestinal microbiota and the availability of a variety of different experimental approaches generated sometimes conflicting and inconsistent data. Manichanh et al (Gut 2006;55:205–11) recently published an extensive study using metagenomic libraries, a novel molecular technique allowing the recruitment of full molecular information of complex microbial habitats. In metagenomic clone libraries with more than 25 000 clones that were generated from faecal samples of healthy subjects and active Crohn's patients, significant loss of indigenous bacteria was found.

The article confirms our report that reduced bacterial diversity seems to be a hallmark of the biofilm in IBD.⁴ Using colonic biopsies we found loss of bacterial diversity of the mucosal microbiota in a large cohort of patients with IBD using different 16S rDNA based detection techniques.⁴ In contrast with Manichanh et al, the taxa of the bacterial phylotypes were determined in our study by sequence homology analysis in clone libraries and not by single strand conformational polymorphism alone.⁴ 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 surprising because the taxonomical classification of metagenomic fragments is based mainly on 16S rDNA anchor genes.

In some aspects there are discrepancies between the different molecular studies. Manichanh et al only demonstrated alterations of the faecal microbiota. As previously demonstrated, different compartments in the intestine contain complex ecological systems that are distinctly different.⁵ Therefore, the composition of the bacterial consortia in human faeces, which contain a high number of transient bacteria, does not fully represent the mucosal microbiota.⁶,⁷ 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 very expensive. Therefore, the number of patients that can be analysed will remain relatively small. Confirmation of reduced bacterial diversity however could now be followed by a deeper analysis of the functional capacities of the bacterial communities. These next steps could 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.