Science 366, 881–886 (2019)

Depending on genetic susceptibility and environmental conditions, the inflammatory heart disease myocarditis can progress into lethal cardiomyopathy, and this transition is associated with autoimmune responses against myosin heavy chain 6 (MYH6). To examine the role of the microbiota as an environmental component driving lethal disease, Gil-Cruz et al. generated mice with myocarditis due to expression of a MYH6-specific T cell receptor (TCRM). The mice only developed lethal disease associated with heart-infiltrating TCRM cells if a microbiota was present; germ-free mice did not develop cardiomyopathy. In silico searching revealed Bacteroides thetaiotaomicron (B. theta) and Bacteroides faecis β-galactosidase (βgal) peptides with high similarity to MYH6, suggesting that B. theta and B. faecis βgal may contribute to myocarditis. The B. theta βgal could activate TCRM T cells, whereas its deletion blocked accumulation of immune cells in the myocardium of TCRM mice. Similarly, antibiotic treatment prevented lethal cardiomyopathy and reduced cardiac inflammation. The authors found that patients with human acute myocarditis had improved symptoms when their B. theta immunoreactivity was reduced. These results suggest that inflammatory cardiomyopathy can be driven by bacterial peptide mimics derived from the intestinal microbiota that activate heart-specific T cells.