Multiomic spatial analysis reveals a distinct mucosa-associated virome

• Published in: Gut microbes Vol. 15; no. 1; p. 2177488
• Main Authors: Yan, Austin, Butcher, James, Schramm, Laetitia, Mack, David R., Stintzi, Alain
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 31.12.2023; Taylor & Francis Group
• Subjects: bacteriophages; Bacteriophages - genetics; Gastrointestinal Microbiome - genetics; gut microbiome; gut mucosa; Humans; Intestinal Mucosa; Metagenomics; Multiomics; phageome; Research Paper; Spatial Analysis; Virome; gut microbiome; phageome; Virome; gut mucosa; bacteriophages
• ISSN: 1949-0976; 1949-0984; 1949-0984
• DOI: 10.1080/19490976.2023.2177488

The human gut virome has been increasingly explored in recent years. However, nearly all virome-sequencing efforts rely solely on fecal samples and few studies leverage multiomic approaches to investigate phage-host relationships. Here, we combine metagenomics, metaviromics, and metatranscriptomics to study virome-bacteriome interactions at the colonic mucosal-luminal interface in a cohort of three individuals with inflammatory bowel disease; non-IBD controls were not included in this study. We show that the mucosal viral population is distinct from the stool virome and houses abundant crAss-like phages that are undetectable by fecal sampling. Through viral protein prediction and metatranscriptomic analysis, we explore viral gene transcription, prophage activation, and the relationship between the presence of integrase and temperate phages in IBD subjects. We also show the impact of deep sequencing on virus recovery and offer guidelines for selecting optimal sequencing depths in future metaviromic studies. Systems biology approaches such as those presented in this report will enhance our understanding of the human virome and its interactions with our microbiome and our health.