Analysis of the microbiome and virome of a gnotobiotic mouse model by Chromosome Conformation Capture

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English. IntroductionThe human gut microbiota houses a complex microbial community which alterations have been associated to various chronic diseases. More recently, variations of intestinal viruses, predominated by bacteriophages, have also been associated with dysbiosis, calling for combined studies of both bacteria and viruses populations.ObjectiveChromosome Conformation Capture (3C) applied on semi-controlled microbial communities generates information on both bacterial and viral populations as well as their interactions through DNA collisions. The goal is to apply this technique to characterize the microbiota of the OMM12 mice.Methodology Here, we applied 3C to analyze in vitro each of the 12 bacteria colonizing the gnotobiotic OMM12 mice as well as the community from longitudinal in vivo samples. In addition, we sequenced the viral fraction of the corresponding samples to identify the population of viruses present in this community.ResultsWe revealed novel information on the diversity of architecture of bacterial chromosomes and their metabolic activities in the gut environment. In particular, we detected the 3D signature of prophage induction amongst which several formed free particles as confirmed by virome sequencing. This shows that 3C data can discriminate functional from cryptic prophages. The comparison between in vitro and in vivo revealed that the gut environment impacted both prophage induction as well as the 3D structure of bacterial genomes.ConclusionsAltogether, the combination of virome and in situ 3C data demonstrates the value of using synthetic communities to characterize the dynamic interactions between bacteriophages and bacteria. These results are in press in Microbiome.