Whole-Virome Analysis Sheds Light on Viral Dark Matter in Inflammatory Bowel Disease

Abstract

The human gut virome is thought to significantly impact the microbiome and human health. However, most virome analyses have been performed on a limited fraction of known viruses. Using whole-virome analysis on a published keystone inflammatory bowel disease (IBD) cohort and an in-house ulcerative colitis dataset, we shed light on the composition of the human gut virome in IBD beyond this identifiable minority. We observe IBD-specific changes to the virome and increased numbers of temperate phage sequences in individuals with Crohn's disease. Unlike prior database-dependent methods, no changes in viral richness were observed. Among IBD subjects, the changes in virome composition reflected alterations in bacterial composition. Furthermore, incorporating both bacteriome and virome composition offered greater classification power between health and disease. This approach to analyzing whole virome across cohorts highlights significant IBD signals, which may be crucial for developing future biomarkers and therapeutics.

Gut Microbiota beyond Bacteria—Mycobiome, Virome, Archaeome, and Eukaryotic Parasites in IBD

“…A large study by Norman et al observed disease-specific changes and reduced diversity of the gut virome in both CD and UC, revealing the primary difference in the IBD-associated virome was the increased richness of Caudovirales phages on a taxonomic level; however, the exact viruses that may give rise to such change were different in CD when compared to UC [88]. A dataset used for this study was recently reanalyzed, confirming IBD-specific changes in the virome, loss of the "core phageome" and increased abundance of induced temperate phages in patients with CD [84]. However, in contrast to the previous report, no changes in viral richness and overall viral alpha diversity were demonstrated.…”

“…Accordingly, there is mounting evidence that the community of phages in the gut is altered when dysbiosis-related disorders are considered, such as IBD and colorectal cancer. In addition, a shift from lysogenic to lytic replication in the population of temperate phages may be linked to the development of IBD [84].…”

“…Furthermore, the changes in the composition of virome mirrored shifts in bacterial composition, while both virome and bacteriome alterations were more pronounced in patients with CD when compared to UC, reflecting the disease severity. Hence, integrating both bacteriome and virome assessment offers higher classification power between healthy and diseased states in IBD [84]. In addition, Fernandes et al revealed how minor patterns and differences in gut virome may be used to differentiate pediatric patients with IBD from healthy controls.…”

A framework for detecting and quantifying relationship alterations in microbial community: Quantifying microbial relationship alteration

“…This statistic takes into account both mean value and covariance matrix, which makes it suitable for reducing two or high dimensional microbial data into a one-dimensional data containing both abundance and relationship information. The T 2 statistic is the multivariate counterpart of the t statistic and widely used in multivariate process consistence monitoring in both industry and biology fields [25,26]. It can be viewed as the generalized distance between the observed vector from the mean vector weighted by the inversion of covariance 5 matrix, − $ & − [27].…”

Phages and Their Role in Gastrointestinal Disease: Focus on Inflammatory Bowel Disease

“…Some hypotheses provided explanations on the basis of experimental data. For instance, Clooney et al hypothesized that one of the conditions contributing to a healthy colon is the presence of a "healthy" core virome [40]. They performed a whole-virome analysis on two IBD virome datasets, one being an in-house UC cohort and the other being a dataset published by Norman et al [29].…”