Both gut microbiota and cytokines act to atherosclerosis in ApoE-/- mice.

Background: Several studies have suggested a role for the gut microbiome and cytokines in atherosclerosis development, but combined analyses of the changes of the gut microbiota and cytokines have not been explored previously.

Methods: We treated ApoE-/- and wild-type mice with a high-fat diet for 12 weeks. The gut microbiome and cytokine composition were analyzed using 16S ribosomal DNA sequencing and RayBio Quantibody Arrays, respectively. GO and KEGG analysis were performed to rationalize the potential mechanisms involved in the process of atherosclerosis.

Results: Gut bacterial characteristics in ApoE-/- mice were clearly separated and 21 gut bacterial clades were detected by the LEfSe analysis showing significant differences during the development of atherosclerosis. The relative abundance of Verrucomicrobia, Bacteroidaceae, Bacteroides, and Akkermansia showed significant positive correlations with serum total cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Additionally, the relative abundance of Ruminococcaceae was positive with the level of HDL and the abundance of Rikenellaceae showed a negative relationship with the level of TG and LDL. Thirteen differentially expressed proteins were identified with P-value < 0.05. CXCL5, FGF2, and E-Selectin were significantly negatively associated with Akkermansia and Verrucomicrobia. Additionally, CXCL5 was significantly negatively correlated with Bacteroides and Bacteroidaceae. Three "cellular component" subcategories, 24 ″molecular function" subcategories, 752 ″biological process" subcategories and 29 statistically remarkable KEGG pathway categories were identified.

Conclusions: Gut microbiota changes of the mice having atherosclerosis and their relationship with the inflammatory status could be one of the major etiological mechanisms underlying atherosclerosis.