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Changes in the gut microbiota are associated with the development of inflammatory bowel diseases, such as Crohn's disease. It has been difficult to reliably identify the specific bacterial taxa that are involved in the pathogenesis of this disease; however, Gevers et al. now define bacterial markers that could be used as diagnostic and prognostic tools.

Crohn's disease is characterized by chronic inflammation of the gut, and previous studies have implicated aberrant immune responses to the gut microbiota as key contributors to pathogenesis. To gain a more thorough understanding of the relationship between the microbiota and disease development, Gevers et al. analysed mucosal biopsy and faecal samples from 447 children with new-onset, untreated Crohn's disease and from 221 healthy controls. Sequencing of the 16S rRNA showed an overall reduction in species diversity in the diseased samples, which was accompanied by increases in the abundances of Enterobacteriaceae, Pasteurellacaea, Veillonellaceae and Fusobacteriaceae and reductions in the abundances of Erysipelotrichales, Bacteroidales and Clostridiales. Interestingly, this dysbiosis was only observed in mucosal samples and not in faecal samples, which indicates that changes in the mucosa-associated microbiota are more important for Crohn's disease pathogenesis than changes in the luminal microbiota. At the time of sample collection, 57 of the children with Crohn's disease had received antibiotics, and the dysbiosis was even more pronounced in these subjects. Thus, the authors suggest that the current practice of antibiotic treatment for Crohn's disease might increase dysbiosis and should be re-evaluated.

dysbiosis was only observed in mucosal samples and not in faecal samples

The authors also found that changes in the abundances of different disease-associated taxa often occurred together; that is, certain bacteria often co-occurred, whereas the presence of other bacteria often excluded specific taxa. To capture these patterns, a microbial disease index that estimates the ratio of all reduced and increased taxa was calculated, and a higher index indicated more severe dysbiosis. This index showed a strong positive correlation with clinical disease severity and a negative correlation with bacterial diversity. The clinical disease state also correlated with the degree of changes in the abundances of bacterial genera in the ileum and rectum. Notably, subjects could be classified into different disease states on the basis of their mucosal microbiome, even from sites that were not directly affected by the disease; for example, the rectal mucosal microbiome could be used to classify children who had only ileal inflammation. As a further diagnostic tool, the authors also developed a model that integrates microbiome data and the clinical characteristics of the patients. This model was better able to predict future disease severity than the clinical data alone.

Taken together, these data highlight the association of specific bacterial taxa with Crohn's disease pathogenesis, which could be exploited as a new diagnostic tool and might provide therapeutic clues.