Ceramide as a key regulatory factor in the impact of dietary inflammatory index on plaque stability

Diet influences plaque stability through its potential to modulate inflammation, a process that involves complex interactions among various lipid metabolites. This study aims to utilize metabolomics to identify key metabolites involved in this pathway and to elucidate the mechanisms by which dietary factors affect plaque stability. The Dietary Inflammatory Index (DII), derived from dietary data, was used to assess the inflammatory potential of individual diets. Propensity score matching categorized serum samples from coronary heart disease (CHD) patients into an anti-inflammatory group (n = 108) and a pro-inflammatory group (n = 108). A comprehensive analysis of lipid profiles was performed using an UPLC-MS/MS detection platform combined with the broad-targeted lipid metabolomics technique, and lipid metabolites with significant differences were screened out. Concurrently, we measured serum levels of inflammatory factors and plaque stability. A Bayesian network model was then applied to elucidate the causal relationships among DII, lipid metabolites, inflammatory factors, and plaque stability. A lipidomics analysis identified 22 differentially expressed lipid metabolites, which were associated with sphingolipid metabolism pathways in the KEGG (Kyoto Encyclopedia of Genes and Genomes) database, particularly involving nine ceramide species. The Bayesian network model exploring the impact of DII on plaque stability comprises 16 nodes and 23 directed arcs. It revealed multiple causal relationships among DII, ceramide species, inflammatory factors, and plaque stability. Specifically, six ceramide species [Cer(d16:0/20:1), Cer(d24:3/15:1), Cer(t14:1/21:0), Cer(t20:0/18:2), Cer(t22:1/16:1), Cer(t26:1/12:1)] and five inflammatory factors (IFN-γ, IL-1β, IL-8, IL-12, IL-13) were found to be involved in these associations. Ceramide species emerged as differential lipid metabolites that distinguish between the anti-inflammatory and pro-inflammatory groups, simultaneously serving as key lipid metabolic products through which diet exerts its influence on plaque stability.