Could an Intestinal Protein Protect the Heart by Acting on Bacteria and Metabolism?

A protein called proline/serine-rich coiled-coil 1 plays a key role in protecting against atherosclerosis, a disease that clogs arteries and promotes heart attacks. Recent research shows that this protein acts by modulating a beneficial gut bacterium, Akkermansia muciniphila, and by influencing the metabolism of tryptophan, an essential amino acid.

In genetically modified mice that do not produce this protein, there is a reduction in the bacterium Akkermansia muciniphila in the gut. This bacterium is known to break down mucins, proteins that protect the intestinal wall, and to produce protective metabolites. Without this protein, the intestinal mucus layer thins, disrupting the bacterial balance and reducing the production of indoleacetic acid, a molecule derived from tryptophan. This molecule activates a cellular receptor called Ahr, which limits inflammation and the formation of atherosclerotic plaques in the arteries.

Scientists discovered that the absence of the protein accelerates the development of atherosclerosis by decreasing indoleacetic acid levels. This leads to an increase in apoptosis, the programmed death of macrophages—immune cells present in atherosclerotic plaques. When these cells die in excess, they make the plaques more unstable and dangerous.

To confirm this mechanism, researchers orally administered the bacterium Akkermansia muciniphila or directly administered indoleacetic acid to mice lacking the protein. In both cases, they observed a significant reduction in atherosclerotic lesions. However, when the Ahr receptor was blocked, the benefits disappeared, proving its central role.

In humans, analyses revealed that individuals with coronary artery disease had lower levels of indoleacetic acid in their blood. These findings suggest that boosting the presence of this bacterium or its metabolites could offer a new therapeutic strategy for preventing cardiovascular diseases, particularly in patients carrying genetic variants affecting this protein.

This study paves the way for targeted approaches, such as dietary supplements or probiotics, to act on the gut microbiota and protect the cardiovascular system. It also highlights the importance of interactions between genetics, gut bacteria, and metabolism in heart health.

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Study Citation

DOI: https://doi.org/10.1038/s12276-026-01668-5

Title: Proline/serine-rich coiled-coil 1 alleviates atherosclerosis via remodeling tryptophan metabolism mediated by Akkermansia muciniphila

Journal: Experimental & Molecular Medicine

Publisher: Springer Science and Business Media LLC

Authors: Qiao Wu; Kexin Hu; Qianqian Wang; Tiantian Luo; Lu Hu; Jichen Liu; Danfeng Zou; Jing Hu; Zhigang Guo