Dataset Information

Multi-Omic Analysis in a Metabolic Syndrome Porcine Model Implicates Arachidonic Acid Metabolism Disorder as a Risk Factor for Atherosclerosis.

ABSTRACT:

Background

The diet-induced gut microbiota dysbiosis has been suggested as a 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 analyzed. 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 the 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.

Conclusions

These findings provide new insights into the relationship between atherothrombosis and regulation of gut microbiota via host metabolomes and will be of potential value for the treatment of cardiovascular diseases in MetS.

SUBMITTER: Xu SS

PROVIDER: S-EPMC8906569 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Multi-Omic Analysis in a Metabolic Syndrome Porcine Model Implicates Arachidonic Acid Metabolism Disorder as a Risk Factor for Atherosclerosis.

Xu Song-Song SS Zhang Xiu-Ling XL Liu Sha-Sha SS Feng Shu-Tang ST Xiang Guang-Ming GM Xu Chang-Jiang CJ Fan Zi-Yao ZY Xu Kui K Wang Nan N Wang Yue Y Che Jing-Jing JJ Liu Zhi-Guo ZG Mu Yu-Lian YL Li Kui K

Frontiers in nutrition 20220223

<h4>Background</h4>The diet-induced gut microbiota dysbiosis has been suggested as a major risk factor for atherothrombosis, however, the detailed mechanism linking these conditions is yet to be fully understood.<h4>Methods</h4>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, an ...[more]

PMID: 35284467

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Project description:BackgroundAging induced chronic systemic inflammatory response is an important risk factor for atherosclerosis (AS) development; however, the detailed mechanism is yet to be elucidated.ObjectiveTo explore the underlying mechanism of how aging aggravates AS advancement.MethodsA young (five-week-old, YM) and aged group (32-week-old, OM) male apoE-/- mice with a high fat diet were used as models, and age-matched male wild-type C57BL/6J (WT) mice were used as controls. AS lesion size, serum lipid profile, cytokines, and gut microbiota-derived LPS were analyzed after 32 weeks of diet intervention. A correlation analysis between the 16S rRNA sequencing of the feces and serum metabolomics profiles was applied to examine the effect of their interactions on AS.ResultsApoE-/- mice developed severe atherosclerosis and inflammation in the aorta compared to the WT groups, and aged apoE-/- mice suffered from a more severe AS lesion than their younger counterparts and had low-grade systemic inflammation. Furthermore, increased levels of serum LPS, decreased levels of SCFAs production, as well as dysfunction of the ileal mucosal barrier were detected in aged mice compared with their younger counterparts. There were significant differences in the intestinal flora composition among the four groups, and harmful bacteria such as Lachnospiraceae_FCS020, Ruminococcaceae_UCG-009, Acetatifactor, Lachnoclostridium and Lactobacillus_gasseri were significantly increased in the aged apoE-/- mice compared with the other groups. Concurrently, metabolomics profiling revealed that components involved in the arachidonic acid (AA) metabolic pathway such as 20-HETE, PGF2α, arachidonic acid, and LTB4 were significantly higher in the aged AS group than in the other groups. This suggested that metabolic abnormalities and disorders of intestinal flora occurred in AS mice.ConclusionsAging not only altered the gut microbiome community but also substantially disturbed metabolic conditions. Our results confirm that AA metabolism is associated with the imbalance of the intestinal flora in the AS lesions of aged mice. These findings may offer new insights regarding the role of gut flora disorders and its consequent metabolite changed in inflammaging during AS development.

Dataset Information

Multi-Omic Analysis in a Metabolic Syndrome Porcine Model Implicates Arachidonic Acid Metabolism Disorder as a Risk Factor for Atherosclerosis.

Background

Methods

Results

Conclusions

Publications

Multi-Omic Analysis in a Metabolic Syndrome Porcine Model Implicates Arachidonic Acid Metabolism Disorder as a Risk Factor for Atherosclerosis.

Similar Datasets

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