Phocaeicola dorei and Phocaeicola vulgatus Protect against Atherosclerosis by Regulating Gut Immunity

AIM: Arteriosclerosis is a condition that leads to coronary artery disease (CAD) and stroke. Basic and clinical studies have suggested a link between the gut microbiota and various diseases, including atherosclerosis. Therefore, we focused on gut microbiota and aimed to develop a probiotic-based treatment for atherosclerosis. METHOD: From 6 to 14 weeks of age, apoE-deficient mice, a mouse model of atherosclerosis, were orally administered with Phocaeicola dorei and Phocaeicola vulgatus or saline five times/week. The diet was changed to a western diet at eight weeks of age. Finally, the mice were sacrificed at 14 weeks of age, and the atherosclerotic lesion area was evaluated. RESULT: Previous studies have shown that atherosclerosis is suppressed by the administration of live type strains (TS) of P. dorei and P. vulgatus in apoE-deficient mice. In this study, we isolated P. vulgatus AF299, which highly expresses commensal colonization factors. Oral administration of P. dorei TS and AF299 to model mice further suppressed atherosclerosis compared to the administration of P. dorei TS and P. vulgatus TS. Genetic analysis of lesion tissues showed that the expression levels of genes associated with inflammatory responses were significantly reduced in mice treated with P. dorei TS and AF299. Moreover, gene expression related to immune response and IgA secretion was increased in the ileum. CONCLUSION: Our results suggest that the bacteria-induced immune response in the gut leads to the suppression of the inflammatory response in atherosclerotic lesions. These results indicate the potential for the development of prophylactic drugs for atherosclerosis.