Gut Dubosiella newyorkensis alleviates noise-related atherosclerosis by reducing N1-methyl-4-pyridone-3-carboxamide.

Environmental noise is ubiquitous in daily life and has emerged as a major risk factor for cardiovascular diseases. Nevertheless, the association between noise exposure and coronary heart disease, as well as the underlying molecular mechanisms, remains poorly understood. Here, analyses of UK Biobank (UKB) data revealed that noise exposure was associated with an increased risk of coronary heart disease. We further demonstrated that noise exposure elevated circulating levels of N1-methyl-4-pyridone-3-carboxamide (4PY) in both humans and rodents. Accumulation of 4PY suppressed endothelial NR4A1 expression, activated NF-κB signaling, facilitated monocyte adhesion and inflammatory cytokine release, and ultimately accelerated atherosclerotic progression. Mechanistically, we found that noise exposure reduced the abundance of Dubosiella newyorkensis (D. newyorkensis) in the gut microbiota of humans. Supplementation with D. newyorkensis upregulated hepatic ACMSD expression, lowered circulating 4PY levels, and alleviated noise-related atherosclerotic progression in mice. Our findings provide mechanistic insights into the therapeutic potential of D. newyorkensis in mitigating noise-related atherosclerosis by reducing circulating 4PY levels. Targeted modulation of the gut microbiota may represent a promising strategy for preventing and managing cardiovascular complications triggered by environmental noise.