The gut microbiota modulates the severity of experimental autoimmune myocarditis 4201

Abstract Description Myocarditis is an inflammatory disease of the myocardium caused by infection-induced autoimmunity toward heart-specific antigens. Although the gut microbiota has been linked to cardiovascular disease, its role in the pathogenesis of myocarditis is unclear. We therefore investigated whether the gut microbiota modulates disease severity in a mouse model of Experimental Autoimmune Myocarditis (EAM). Germ-free mice were colonized with one of three distinct microbiomes (M31B, W116 or MC608) prior to inducing EAM with adjuvanted myosin. Mice harboring MC608 had significantly higher inflammatory heart scores and myosin-specific autoimmune responses versus mice carrying M31B. Mice with severe signs of EAM also experienced alterations in composition of their microbiota, including a significant decrease in Lactobacillus. We further observed negative correlations between EAM severity and both L. reuteri and L. taiwanensis. To test for protective effects of these species, we inoculated Lactobacillus-deficient mice with both L. reuteri and L. taiwanensis prior to EAM induction. Treatment with both lactobacilli significantly decreased myosin-specific IFN-γ and IgG responses compared to controls. Altogether, these results show that the gut microbiota modulates EAM severity and autoreactive responses. Moreover, L. reuteri and L. taiwanensis provide protection against severe EAM, suggesting that live biotherapeutics may be a beneficial adjunct therapy for myocarditis patients. Funding Sources This project was supported by an NU Collaboration seed grant. Topic Categories Basic Autoimmunity (BA)