Abstract 4143104: Atherosclerotic features of plaque instability are transmitted via gut microbial transplantation

Background: Gut microbiota have been suggested as a causative agent of atherosclerosis mainly by converting dietary and endogenous molecules into active metabolites like the trimethylamine N-oxide (TMAO). Nevertheless, the relationship between gut microbiota and plaque features has not been well documented. In this study, we tested the hypothesis that gut microbial transplantation can transmit atherosclerotic plaque characteristics. Methods and Results: In a fecal microbiota transplantation mouse model, the colonization of gut microbiota from patients with acute coronary syndrome (ACS, n=9), chronic coronary syndrome (CCS, n=11) and control subjects (CTRL, n=8) was evaluated and plaque features of stability were assessed. Transplantation was performed into ApoE KO mice fed a diet containing 1% choline or a standard diet. Initially, resident intestinal microbes were suppressed using antibiotics, followed by the administration of fecal oral gavages from human donors over a period of 12 weeks. Firstly, a significant positive correlation was detected between TMAO serum levels assessed by UPLC-MS/MS system and atherosclerotic lesion formation measured by Oil Red O staining of aortic root cross-sections; however, no correlations were identified with plaque instability. Plaque composition was analyzed using necrotic core area and fibrous cap thickness as primary readouts of plaque vulnerability. Interestingly, microbiota from ACS patients significantly decreased plaque stability as showed by increased necrotic core and fibrous cap thinning. Further, it decreased α-SMA + cell population and increased MMP2 staining, indicating intraplaque metalloprotease activity. Gut microbiota composition was evaluated using 16S rRNA sequencing of ApoE KO mice fecal samples. In ACS transplanted mice, 14 bacterial genera were positively associated with larger necrotic core and 6 bacterial genera with MMP2. In CCS transplanted mice, 6 bacterial genera showed negative correlations with necrotic core size and 2 bacterial genera positively correlated with α-SMA + cells. Conclusions: In conclusion, we identified bacteria significantly associated with the vulnerable plaque phenotype, which provides potential insights to modulate atherosclerotic plaque composition by influencing the gut microbiota.