This study found that imidazole propionate (ImP), a metabolite produced by gut microorganisms, is associated with atherosclerosis in mice and humans. While the human data is correlational and derived from cohorts of limited diversity (Spanish and Swedish populations), experiments in mouse models suggest a causal role for ImP in driving atherosclerosis, particularly through activation of the immune response and the mTOR pathway in myeloid cells. Blocking ImP's interaction with the I1R receptor in mice prevented atherosclerosis development.

Some authors are listed as inventors on a patent application related to antagonists of I1R. FB receives research funding from Biogaia AB and Novo Nordisk A/S, is a co-founder and shareholder of Roxbiosens Inc., and is on the scientific advisory board of Bactolife A/S. FB, KRB, and AC are co-founders and shareholders of Implexion Pharma AB.

This is a strong study with compelling findings in mouse models and human cohorts, suggesting a potential new target for atherosclerosis therapy. The research employs appropriate methodology and provides valuable insights into the role of gut microbiota in cardiovascular disease. However, limitations related to generalizability and mechanistic understanding in humans prevent a perfect score.