Natto consumption suppresses atherosclerotic plaque progression in LDL receptor-deficient mice transplanted with iRFP-expressing hematopoietic cells

Natto, known for its high vitamin K content, has been shown to be effective in suppressing atherosclerosis through large-scale clinical trials, yet the mechanism of suppression is unknown. In this study, we used a previously reported mouse model, transplanting the bone marrow of mice expressing Infra-red fluorescent protein (iRFP) into LDLR-deficient mice, allowing unique and non-invasive observation of foam cell iRFP in atherosclerotic lesions. We meticulously examined the effects of three different natto types with varying vitamin K levels on atherosclerosis in these mice. Particularly, high vitamin K natto significantly reduced aortic staining and iRFP fluorescence, indicative of decreased atherosclerosis. Furthermore, mice administered natto showed changes in gut microbiota, including an increase in natto bacteria within the cecum, and a significant reduction in serum CCL2 expression. In experiments with LPS-stimulated macrophages, adding natto decreased CCL2 expression and increased anti-inflammatory cytokine IL-10 expression. This suggests that natto suppresses intestinal inflammation and reduces CCL2 expression, thereby acting to inhibit atherosclerosis.