AUTHOR=Xu Song-Song , Zhang Xiu-Ling , Liu Sha-Sha , Feng Shu-Tang , Xiang Guang-Ming , Xu Chang-Jiang , Fan Zi-Yao , Xu Kui , Wang Nan , Wang Yue , Che Jing-Jing , Liu Zhi-Guo , Mu Yu-Lian , Li Kui TITLE=Multi-Omic Analysis in a Metabolic Syndrome Porcine Model Implicates Arachidonic Acid Metabolism Disorder as a Risk Factor for Atherosclerosis JOURNAL=Frontiers in Nutrition VOLUME=Volume 9 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.807118 DOI=10.3389/fnut.2022.807118 ISSN=2296-861X ABSTRACT=Background: The diet-induced gut microbiota dysbiosis has been suggested as major risk factor for atherothrombosis, however, the detailed mechanism linking these conditions is yet to be fully understood. Methods: We established a long-term excessive-energy diet-induced metabolic syndrome (MetS) inbred Wuzhishan minipig model, which is characterized by its genetic stability, small size, and human-like physiology. The metabolic parameters, atherosclerotic lesions, gut microbiome, and host transcriptome were analysed. Metabolomics profiling revealed a linkage between gut microbiota and atherothrombosis. Results: We showed that white atheromatous plaque was clearly visible on abdominal aorta in the MetS model. Furthermore, using metagenome and metatranscriptome sequencing, we discovered that long-term excessive energy intake altered the local intestinal microbiota composition and transcriptional profile, which was most dramatically illustrated by the reduced abundance of SCFAs-producing bacteria including Bacteroides, Lachnospiraceae and Ruminococcaceae in the MetS model. Liver and abdominal aorta transcriptomes in the MetS model indicate that the diet-induced gut microbiota dysbiosis activated host chronic inflammatory responses and significantly upregulated the expression of genes related to arachidonic acid-dependent signaling pathways. Notably, metabolomics profiling further revealed an intimate linkage between arachidonic acid metabolism and atherothrombosis in the host-gut microbial metabolism axis.