Exploring the gut virome in fecal immunochemical test stool samples reveals novel associations with lifestyle in a large population-based study

Abstract

ABSTRACTStool samples for fecal immunochemical tests (FIT) are collected in large numbers worldwide as part of colorectal cancer screening programs, but to our knowledge, the utility of these samples for virome studies is still unexplored. Employing FIT samples from 1034 CRCbiome participants, recruited from a Norwegian colorectal cancer screening study, we identified and annotated more than 18000 virus clusters (vOTUs), using shotgun metagenome sequencing. Only six percent of vOTUs were assigned to a known taxonomic family, withMicroviridaebeing the most prevalent viral family. Genome integration state was family-associated, and the majority of identified viruses were unintegrated. Linking individual profiles to comprehensive lifestyle and demographic data showed 17/25 of the variables to be associated with the gut virome. Physical activity, smoking, and dietary fiber consumption exhibited strong and consistent associations with both diversity and relative abundance of individual vOTUs, as well as with enrichment for auxiliary metabolic genes.We demonstrate the suitability of FIT samples for virome analysis, opening an opportunity for large-scale studies of this yet enigmatic part of the gut microbiome. The diverse viral populations and their connections to the individual lifestyle uncovered herein paves the way for further exploration of the role of the gut virome in health and disease.