MISSILE project: MIcrobiome-derived metabolites and cardiovascular involvement in SyStemIc Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease which affects multiple organ systems and often causes severe complications such as renal failure, neurological disturbances, peripheral cytopenia and systemic symptoms. Cardiovascular events are the major determinant of SLE-related morbidity and mortality, also in early age and particularly in patients with active lupus nephritis, but to date their pathogenetic mechanisms are still largely unknown. Experimental and clinical models suggest that SLE patients carry gut microbiome (GM) dysbiosis, which might play a role in disease activity. The role of GM in determining the cardiovascular risk in autoimmune diseases has begun to be appreciated in the general population in recent years. Specifically, levels of trimethylamine N-oxide (TMAO), an important GM-dependent metabolite, has been suggested to correlate with the risk of cardiovascular events, mostly atherothrombotic. To date, no studies have investigated the role of TMAO in mediating cardiovascular manifestations in SLE. On these bases, an observational, monocentric, cross-sectional study was conducted on SLE patients to assess levels of TMAO and their association with the occurrence of cardiovascular manifestations and the atherosclerotic state. Moreover, the association of traditional cardiovascular risk factors, inflammatory markers and the immunologic profile with TMAO levels was investigated. The study could provide new information on the role of GM-derived metabolites in mediating cardiovascular risk in SLE.