Insight into the gut virome in patients with multiple sclerosis

Abstract

AbstractMultiple 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 ofMicroviridaeandMyoviridaebacteriophage, and eukaryotic virus such asHerpesviridaeandPhycodnaviridaein RRMS patients compared to HC. Non-MDA methods showed reduction in relative abundance ofSiphoviridaebacteriophage and eukaryotic viruses such asAckermannviridae,Demerecviridae,Dicistroviridae,Herelleviridae,Mesnidovirineaein RRMS patients. Cluster analysis revealed that the whole virome family was dominated byPodoviridaeandSiphoviridaeclusters. Comparing dietary metadata between these clusters, RRMS patients in theSiphoviridae-dominated Cluster B showed significantly higher consumption of refined grains and salad dressings compared to those in thePodoviridae-dominated Cluster A. Correlation analysis between gut viruses and bacteria demonstrated thatSiphoviridaeexhibited positive correlations with many different bacterial genera. Conversely,Microviridaedisplayed 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.