Insight into the gut virome in patients with multiple sclerosis

Abstract

Multiple sclerosis (MS) is an autoimmune condition associated with dysbiosis in the bacterial element of microbiome, yet limited information exists regarding dysbiosis in the virome. In this study, we examined the virome in 20 relapsing-remitting MS (RRMS) patients and 22 healthy controls (HC). We extracted virus-like particles (VLP) genomic DNA through sequential filtration, followed by deep metagenomic sequencing approaches with and without multiple displacement amplification (MDA). We found significantly lower diversity in the gut virome of RRMS patients relative to HC, consistent across both sequencing methods. MDA method identified reduced relative abundance of Microviridae and Myoviridae bacteriophage, and eukaryotic virus such as Herpesviridae and Phycodnaviridae in RRMS patients compared to HC. Non-MDA methods showed reduction in relative abundance of Siphoviridae bacteriophage and eukaryotic viruses such as Ackermannviridae, Demerecviridae, Dicistroviridae, Herelleviridae, Mesnidovirineae in RRMS patients. Cluster analysis revealed that the whole virome family was dominated by Podoviridae and Siphoviridae clusters. Comparing dietary metadata between these clusters, RRMS patients in the Siphoviridae-dominated Cluster B showed significantly higher consumption of refined grains and salad dressings compared to those in the Podoviridae-dominated Cluster A. Correlation analysis between gut viruses and bacteria demonstrated that Siphoviridae exhibited positive correlations with many different bacterial genera. Conversely, Microviridae displayed negative correlations with many different bacterial genera. These findings underscore the alterations in viral diversity and taxonomic composition of the gut virome in RRMS patients. Our study represents the first step in understanding the gut virome in MS patients, providing a groundwork for future research on the role of the gut virome in the context of MS.