The role of parental osmotic stress and vanishing taxa on the exacerbation of autoimmune neuroinflammation 4442

Abstract Description Industrialized lifestyles are associated with increased risk of chronic inflammatory disorders and reduced microbiota diversity compared to traditional populations. Laxative treatments (LT) reduce microbial diversity, yet the effects of LT on autoimmune disease remain unknown. We hypothesized that LT may exacerbate experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. We found that the microbiota of adult offspring of laxative treated (LTO) parents was significantly altered, including loss of Muribaculaceae intestinale (Mb) and several Clostridia species. Further, the severity and incidence of EAE was reduced in LTO mice compared to offspring from parents with no LT (NTO). At peak disease, CD4+ T cells from the central nervous system (CNS) of NTO mice expressed significantly more IFNγ, IL-17A, and GM-CSF compared to LTO mice and CNS microglia (CD45midCD11b+P2RY12+) from NTO mice had higher expression of the proliferation marker Ki67 and the damage response marker Clec7a. These data indicate that recruitment and activation of CNS immune cells is impaired in LTO mice. Adding Mb isolates to adult LTO mice prior to EAE induction increased EAE disease severity compared to LTO mice. Finally, LT in NTO prior to EAE does not ameliorate disease, suggesting that immune education in the presence of Mb and Clostridia species, and the physical presence of Mb in adult mice, prime inflammatory pathways that enhance susceptibility to autoimmune disease. Funding Sources Research in the Osborne lab is supported by the Canadian Institutes of Health Research, Multiple Sclerosis Canada, the Weston and Praespero Foundations. SP is supported through an endMS Doctoral Award. Topic Categories Neuroimmunology (NEUR)