Interpersonal variability of the human gut virome confounds disease signal detection in IBD

Author:

Stockdale Stephen R.,Shkoporov Andrey N.ORCID,Khokhlova Ekaterina V.,Daly Karen M.,McDonnell Siobhan A.,O’ Regan Orla,Nolan James A.,Sutton Thomas D. S.,Clooney Adam G.,Ryan Feargal J.,Sheehan Donal,Lavelle Aonghus,Draper Lorraine A.ORCID,Shanahan FergusORCID,Ross R. Paul,Hill ColinORCID

Abstract

AbstractViruses are increasingly recognised as important components of the human microbiome, fulfilling numerous ecological roles including bacterial predation, immune stimulation, genetic diversification, horizontal gene transfer, microbial interactions, and augmentation of metabolic functions. However, our current view of the human gut virome is tainted by previous sequencing requirements that necessitated the amplification of starting nucleic acids. In this study, we performed an original longitudinal analysis of 40 healthy control, 19 Crohn’s disease, and 20 ulcerative colitis viromes over three time points without an amplification bias, which revealed and highlighted the interpersonal individuality of the human gut virome. In contrast to a 16 S rRNA gene analysis of matched samples, we show that α- and β-diversity metrics of unamplified viromes are not as efficient at discerning controls from patients with inflammatory bowel disease. Additionally, we explored the intrinsic properties of unamplified gut viromes and show there is considerable interpersonal variability in viral taxa, infrequent longitudinal persistence of intrapersonal viruses, and vast fluctuations in the abundance of temporal viruses. Together, these properties of unamplified faecal viromes confound the ability to discern disease associations but significantly advance toward an unbiased and accurate representation of the human gut virome.

Publisher

Springer Science and Business Media LLC

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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