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DOP018. Low microbial diversity in Crohn's disease is due to striking depletion of unknown species

N. Borruel1, H.B. Nielsen2, F. Casellas1, C. Manichanh3, E. Varela3, M. Antolín3, A. Torrejón1, V. Robles1, P. Nos4, X. Calvet5, F. Guarner1, MetaHIT Consortium6, 1Hospital Vall d'Hebron, Crohn's and Colitis Attention Unit. Digestive System Research Unit, Barcelona, Spain, 2Technical University of Denmark, Center for Biological Sequence Analysis, Department of Systems Biology, Lyngby, Denmark, 3Hospital Vall d'Hebron, Digestive System Research Unit, Barcelona, Spain, 4Hospital Universitari i Politècnic La Fe, Servicio de Medicina Digestiva, Valencia, Spain, 5Corporació Sanitària Parc Taulí, Servei d'Aparell Digestiu, Sabadell, Spain, 6MetaHIT Network, Partner Centres, Paris, France

Background

Analysis of 16SrRNA gene sequences in biological samples allows estimation of bacterial taxonomy, but does not report about functionality (genetic resources) or presence of non-bacterial members (viruses, yeasts or protists) in the community. To overcome these limitations, the entire genomic material of the sample can be sequenced and compared with reference genomes.

Methods

We studied whole-genome shotgun Illumina sequences in 381 faecal samples from 318 individuals of the MetaHIT cohort (177 from Copenhagen, 141 from Barcelona; 153 from healthy subjects, 83 overweight, 124 ulcerative colitis, and 21 Crohn's disease).

Results

A catalogue of 3.9 million non-redundant genes was generated, of which 69.7% were recognized as bacterial, 2.2% as archaea, 1.2% of viruses or phages, 0.6% of protists and 0.2% of yeasts, but there was no known reference for 26% of genes (!). Furthermore, only 10% of the genes could be assigned at species level with 95% identity. In order to detect non-referenced taxonomical entities, genes that correlated in abundance across different individuals were clustered in groups. Thus, 7,381 co-abundant gene groups were detected; 6,640 are small clusters (less than 700 genes, median 44) corresponding to viruses or extra-chromosomal genes (phages, plasmids or genomic islands). The remaining 741 groups are large clusters (called metagenomic species or MGS, with a median of 1,700 genes) and correspond to bacterial species or archaea of which only 115 MGS are fully identifiable (95%) in reference genomes, 108 MGS are partially identifiable and 518 MGS represent unknown species. In samples from patients with Crohn's disease, a marked depletion of unknown MGS was observed (71, 95% CI 60–82) as compared to healthy controls (168, 162–176). Likewise, ulcerative colitis patients (149, 141–157) and overweight subjects (155, 146–164) showed significant depletion, although less pronounced.

Conclusion

Low diversity in the intestinal microbial ecosystem of patients with Crohn's disease is mainly due to depletion of unknown microbial species.