Metagenomic Analysis of Crohn's Disease Patients Identifies Changes in the Virome and Microbiome Related to Disease Status and Therapy, and Detects Potential Interactions and Biomarkers.

Abstract

The aim of this study was to survey the bacterial and viral communities in different types of samples from patients with Crohn's disease (CD) at different stages of the disease to relate their distribution with the origin and progression of this disorder. A total of 42 fecal samples and 15 biopsies from 20 patients with CD and 20 healthy control individuals were collected for bacterial 16S rRNA gene profiling and DNA/RNA virome metagenomic analysis through 454 pyrosequencing. Their composition, abundance, and diversity were analyzed, and comparisons of disease status, patient status, and sample origin were used to determine statistical differences between the groups. Bacterial composition and relative abundance in new-onset patients with CD differed markedly from control individuals. Individual variability and sample origin had a stronger impact on viral communities than the disease, contrary to what was observed for bacterial populations although increased numbers of overrepresented viruses were observed in feces from patients with CD. Correlation-based networks were constructed to show potential relations between bacteria and between those and viruses. The bacterial community reflects the disease status of individuals more accurately than their viral counterparts. However, numerous viral biomarkers specifically associated with CD disease were identified. Because viruses can modulate bacterial communities, the correlation networks between both communities constitute a step forward in unraveling their interactions under normal and CD disease conditions.