Distinct association of microbiota with CNS immune gene expressions between virus-induced acute myelitis versus chronic inflammatory demyelination

Virus infections have been associated with acute and chronic inflammatory central nervous system (CNS) diseases, e.g., acute flaccid myelitis (AFM) and multiple sclerosis (MS), where animal models support the pathogenic roles of viruses. In the spinal cord, Theiler’s murine encephalomyelitis virus (TMEV) induces an AFM-like disease with gray matter inflammation during the acute phase 1-week post infection (p.i.) and an MS-like disease with white matter inflammation during the chronic phase 1-month p.i. Gut microbiota can affect immune responses contributing to pathology in remote organs including the CNS. Although gut microbiota have been proposed to play a role in MS pathophysiology, its role in AFM is unclear. We infected SJL/J mice with TMEV, harvested feces and spinal cords on days 4 (before onset), 7 (acute phase), and 35 (chronic phase) p.i., and examined fecal microbiota by 16S rRNA sequencing and CNS transcriptome by RNA sequencing. TMEV infection induced neither decreased microbial diversity nor changed overall microbiome patterns, unlike previous findings in other microbiota-associated diseases. We found significantly increased abundance of the genera Marvinbryantia on days 7 and 35, and Coprococcus on day 35, whose pattern matching with CNS transcriptome showed strong correlations: Marvinbryantia with eight T cell receptor (TCR) genes on day 7, and with 10 immunoglobulin (Ig) genes including Ighd4-1 on day 35; and Coprococcus with gene expressions of several major histocompatibility complex (MHC), complements as well as TCR and Ig. Metagenomic analysis predicted the changes in arachidonic acid and ether lipid metabolism due to the changes in five taxa and two taxa of bacteria belong to the order Clostridiales, respectively. Therefore, acute and chronic CNS inflammation could be influenced by the changes in a limited number of distinct bacteria, but not in overall gut microbiota.