Deposition and hydrolysis of serine dipeptide lipids of Bacteroidetes bacteria in human arteries: relationship to atherosclerosis

Abstract

Multiple reaction monitoring-MS analysis of lipid extracts from human carotid endarterectomy and carotid artery samples from young individuals consistently demonstrated the presence of bacterial serine dipeptide lipid classes, including Lipid 654, an agonist for human and mouse Toll-like receptor (TLR)2, and Lipid 430, the deacylated product of Lipid 654. The relative levels of Lipid 654 and Lipid 430 were also determined in common oral and intestinal bacteria from the phylum Bacteroidetes and human serum and brain samples from healthy adults. The median Lipid 430/Lipid 654 ratio observed in carotid endarterectomy samples was significantly higher than the median ratio in lipid extracts of common oral and intestinal Bacteroidetes bacteria, and serum and brain samples from healthy subjects. More importantly, the median Lipid 430/Lipid 654 ratio was significantly elevated in carotid endarterectomies when compared with control artery samples. Our results indicate that deacylation of Lipid 654 to Lipid 430 likely occurs in diseased artery walls due to phospholipase A2 enzyme activity. These results suggest that commensal Bacteriodetes bacteria of the gut and the oral cavity may contribute to the pathogenesis of TLR2-dependent atherosclerosis through serine dipeptide lipid deposition and metabolism in artery walls.

Mediators between oral dysbiosis and cardiovascular diseases

“…For example, bacteria of the phylum Bacteroidetes produce serine dipeptide lipids that are recognized by TLR‐2 . These lipid forms are common in some P. gingivalis strains and they have also been recovered in carotid endarterectomy samples .…”

Relationship between serine dipeptide lipids of commensal Bacteroidetes and atherosclerosis

“…An interesting study, assessing the relationship between serine dipeptide lipids of Bacteroidetes bacteria in human arteries and atherosclerosis, was recently published in the Journal of Lipid Research [11]. The new ideas advocated here add to our understanding of the capacity of such bacteria to contribute to atherosclerosis.…”

“…The relative abundance of these lipids was examined in oral and intestinal bacteria from the phylum Bacteroidetes and from human serum and brain samples from healthy adults [11]. These analyses showed that the median Lipid 430/Lipid 654 ratio in carotid endarterectomy samples was significantly higher than the median lipid ratio in extracts from common oral and intestinal Bacteroidetes bacteria, as well as in extracts from serum and brain samples from healthy subjects.…”

“…Although the study by Nemati et al [11] has brought up new and interesting thoughts on the pathogenesis of atherosclerosis, other surface molecules of these bacteria may also influence this condition [23]. It should also be kept in mind that much of the pathogenicity of P. gingivalis is surprisingly related to its overall immunosuppression of the host [24].…”

“…It should also be kept in mind that much of the pathogenicity of P. gingivalis is surprisingly related to its overall immunosuppression of the host [24]. Nevertheless, the study by Nemati et al [11] has certainly extended our view on the possible pathogenesis of Bacteroidetes in atherosclerosis where serine dipeptide lipids may be hitherto unappreciated virulence factors.…”