Abstract
Viruses are common components of the intestinal microbiome, modulating host bacterial metabolism and interacting with the immune system, with a possible role in the pathogenesis of immune-mediated diseases such as celiac disease (CeD). The objective of this study was to characterize the virome profile in children with new-onset CeD. We used metagenomic analysis of viral DNA in mucosal and fecal samples from children with CeD and controls and performed sequencing using the Nextera XT library preparation kit. Abundance log2 fold changes were calculated using differential expression and linear discriminant effect size. Shannon alpha and Bray–Curtis beta diversity were determined. A total of 40 children with CeD and 39 controls were included. We found viral dysbiosis in both fecal and mucosal samples. Examples of significantly more abundant species in fecal samples of children with CeD included Human polyomavirus 2, Enterobacteria phage mEpX1, and Enterobacteria phage mEpX2; whereas less abundant species included Lactococcus phages ul36 and Streptococcus phage Abc2. In mucosal samples however, no species were significantly associated with CeD. Shannon alpha diversity was not significantly different between CeD and non-CeD groups and Bray–Curtis beta diversity showed no significant separation between CeD and non-CeD samples in either mucosal or stool samples, whereas separation was clear in all samples. We identified significant viral dysbiosis in children with CeD, suggesting a potential role in the pathogenesis of CeD indicating the need for further studies.
Highlights
Viruses are common components of the intestinal microbiome, among which, bacteriophages are the most common [1, 2]
Viral dysbiosis and celiac disease bacterial metabolism and interact with the immune system, triggering the innate and adaptive immune systems by employing similar mechanisms as those used by bacteria, suggesting a role in chronic inflammatory conditions [3, 4]
It has been suggested that infection with RNA and possibly DNA eukaryotic viruses may cause a transient disease resulting in loss of tolerance to gluten and development of Celiac disease (CeD) in susceptible individuals [22]
Summary
Viruses are common components of the intestinal microbiome, among which, bacteriophages (viruses that infect bacteria) are the most common [1, 2]. Viral dysbiosis and celiac disease bacterial metabolism and interact with the immune system, triggering the innate and adaptive immune systems by employing similar mechanisms as those used by bacteria, suggesting a role in chronic inflammatory conditions [3, 4]. Gluten exposure alone does not trigger CeD in all genetically susceptible individuals, suggesting a role of additional factors. In this context, microbiota have been reported as one of the most important environmental factors in CeD. It has been suggested that infection with RNA and possibly DNA eukaryotic viruses may cause a transient disease resulting in loss of tolerance to gluten and development of CeD in susceptible individuals [22].
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