Imidazole propionate is a driver and therapeutic target in atherosclerosis
www.nature.com/articles/s41586-025-09263-w
While some bacteria may boost the immune system and drive better immunotherapy outcomes in cancer patients, other bacteria produce molecules that promote inflammation. In fact, the same molecule can be beneficial in one context (stimulating the immune system) and detrimental in another (over-stimulating the immune system). In other words, inflammation is a good thing to fight acute conditions (tumor, infection) but not good if it constant.
This article in Nature by a team led by @david sancho from @Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain reports on one bacterial metabolite, imidazole propionate (ImP) alone is sufficient to induce and aggravate atherosclerosis in a mouse model (Apoe -/- mice). It works by binding a receptor of certain immune cells: by blocking this connection, the authors were able to inhibit the development of atherosclerosis induced by either ImP or a high-cholesterol diet. Receptor activation induces p-S6 and proinflammatory cytokine production, consistent with mTOR activation in macrophages contributing to atherosclerosis: immune cell recruitment to fatty plaques in blood vessels increases plaque size through the build-up of cholesterol and immune cells.
As far as the microbial culprits are concerned, plasma ImP concentration was associated with a relative enrichment of Escherichia and Shigella, or Eubacterium in mice, and the relative abundance of Veillonella and Acidaminococcus in humans. Previous studies of AMP had identified Clostridium bolteae, Clostridium symbiosum, and Ruminococcus gnavus as ImP contributors (Molinaro, A., Bel Lassen, P., Henricsson, M. et al. Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology. Nat Commun 11, 5881 (2020))
Perhaps the most striking observation is that atherosclerosis can be induced by ImP without change in cholesterol: this may explain why lipid-lowering interventions are not sufficient. Given that atherosclerosis is one of the main causes of cardiovascular diseases, that’s an important and promising discovery.
Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology : www.nature.com/articles/s41467-020-19589-w