Abstract
Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances.
Highlights
The human microbiome is a highly complex community of microorganisms consisting of diverse bacteria, archaea, and eukaryota, and of an immense population of viruses [1,2,3,4,5,6]
The use of multiple displacement amplification (MDA) when quantities of viral DNA recovered are limited can introduce biases into viromes [17,18]. Another potentially more significant limitation in the analysis of viral communities has been a relative lack of tools available for characterizing their ecology and their diversity compared to the analysis of bacterial communities which can be done with a number of tools such as QIIME [19] and Mothur [20], which have greatly facilitated the characterization of bacterial biota using 16S rRNA
We used BLASTN to compare all viromes to the RDP 16S rRNA database and a human reference genome and found that all were free of 16S rRNA homologues, and relatively few were homologous to human DNA
Summary
The human microbiome is a highly complex community of microorganisms consisting of diverse bacteria, archaea, and eukaryota (fungi), and of an immense population of viruses [1,2,3,4,5,6]. The use of multiple displacement amplification (MDA) when quantities of viral DNA recovered are limited can introduce biases into viromes [17,18]. Another potentially more significant limitation in the analysis of viral communities has been a relative lack of tools available for characterizing their ecology and their diversity compared to the analysis of bacterial communities which can be done with a number of tools such as QIIME [19] and Mothur [20], which have greatly facilitated the characterization of bacterial biota using 16S rRNA. PHACCS, estimates viral diversity based on predictions of population diversity using contig spectra, but requires estimates of mean virus genome lengths in the population to predict diversity [22]
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