Abstract
BackgroundViral metagenomic studies have suggested a role for bacteriophages in intestinal dysbiosis associated with several human diseases. However, interpretation of viral metagenomic studies is limited by the lack of knowledge of phages infecting major human gut commensal bacteria, such as Faecalibacterium prausnitzii, a bacterial symbiont repeatedly found depleted in inflammatory bowel disease (IBD) patients. In particular, no complete genomes of phages infecting F. prausnitzii are present in viral databases.MethodsWe identified 18 prophages in 15 genomes of F. prausnitzii, used comparative genomics to define eight phage clades, and annotated the genome of the type phage of each clade. For two of the phages, we studied prophage induction in vitro and in vivo in mice. Finally, we aligned reads from already published viral metagenomic data onto the newly identified phages.ResultsWe show that each phage clade represents a novel viral genus and that a surprisingly large fraction of them (10 of the 18 phages) codes for a diversity-generating retroelement, which could contribute to their adaptation to the digestive tract environment. We obtained either experimental or in silico evidence of activity for at least one member of each genus. In addition, four of these phages are either significantly more prevalent or more abundant in stools of IBD patients than in those of healthy controls.ConclusionSince IBD patients generally have less F. prausnitzii in their microbiota than healthy controls, the higher prevalence or abundance of some of its phages may indicate that they are activated during disease. This in turn suggests that phages could trigger or aggravate F. prausnitzii depletion in patients. Our results show that prophage detection in sequenced strains of the microbiota can usefully complement viral metagenomic studies.
Highlights
Viral metagenomic studies have suggested a role for bacteriophages in intestinal dysbiosis associated with several human diseases
According to current taxonomic metrics whereby phages within a genus share at least 40% of their proteins, and phages of the same species have more than 95% identity on the whole genome [24, 25], the 23 prophages correspond to 18 species and 8 genera (Additional file 2), for which we propose names (Table 1 and Fig. 1)
Some F. prausnitzii phages are more abundant in the gut viromes of inflammatory bowel disease (IBD) subjects To evaluate the activity of the identified prophages in the human gastrointestinal tract (GIT), we investigated the sequences obtained from the viral fraction of 171 fecal samples from a large cohort of 52 IBD patients and 21 healthy controls [18]
Summary
Viral metagenomic studies have suggested a role for bacteriophages in intestinal dysbiosis associated with several human diseases. Interpretation of viral metagenomic studies is limited by the lack of knowledge of phages infecting major human gut commensal bacteria, such as Faecalibacterium prausnitzii, a bacterial symbiont repeatedly found depleted in inflammatory bowel disease (IBD) patients. A few genes continue to be expressed, including the repressor of the lytic cycle and a class of genes known as morons whose expression often modifies the physiology of the host bacterium. In this way, prophages can modify numerous phenotypes of their bacterial host, such as resistance against phage attack, stress resistance, pathogenicity, or ability to form biofilms [11, 12]. Active prophages can be highly detrimental to their host in some inducing conditions [13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
