Distinct roles for dietary lipids and Porphyromonas gingivalis infection on atherosclerosis progression and the gut microbiota
| Autor: | Alexandra M. Simas, Robin R. Ingalls, Ellen O. Weinberg, Caroline A. Genco, Carolyn D. Kramer, Xianbao He |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Inflammation Gut flora Microbiology Article 03 medical and health sciences 0302 clinical medicine Immune system Immunity medicine Animals Endothelial dysfunction Porphyromonas gingivalis Vascular tissue biology Bacterial Infections Atherosclerosis Lipid Metabolism biology.organism_classification medicine.disease Gastrointestinal Microbiome Gastrointestinal Tract Mice Inbred C57BL Disease Models Animal 030104 developmental biology Infectious Diseases 030220 oncology & carcinogenesis Immunology medicine.symptom Lipoprotein |
| Zdroj: | Anaerobe. 45:19-30 |
| ISSN: | 1075-9964 |
| Popis: | Mounting evidence in humans supports an etiological role for the microbiota in inflammatory atherosclerosis. Atherosclerosis is a progressive disease characterized by accumulation of inflammatory cells and lipids in vascular tissue. While retention of lipoprotein into the sub-endothelial vascular layer is believed to be the initiating stimulus leading to the development of atherosclerosis, activation of multiple pathways related to vascular inflammation and endothelial dysfunction sustain the process by stimulating recruitment of leukocytes and immune cells into the sub-endothelial layer. The Gram-negative oral pathogen Porphyromonas gingivalis has been associated with the development and acceleration of atherosclerosis in humans and these observations have been validated in animal models. It has been proposed that common mechanisms of immune signaling link stimulation by lipids and pathogens to vascular inflammation. Despite the common outcome of P. gingivalis and lipid feeding on atherosclerosis progression, we established that these pro-atherogenic stimuli induced distinct gene signatures in the ApoE-/- mouse model of atherosclerosis. In this study, we further defined the distinct roles of dietary lipids and P. gingivalis infection on atherosclerosis progression and the gut microbiota. We demonstrate that diet-induced lipid lowering resulted in less atherosclerotic plaque in ApoE-/- mice compared to ApoE-/- mice continuously fed a Western diet. However, the effect of diet-induced lipid lowering on plaque accumulation was blunted by P. gingivalis infection. Using principal component analysis and hierarchical clustering, we demonstrate that dietary intervention as well as P. gingivalis infection result in distinct bacterial communities in fecal and cecal samples of ApoE-/- mice as compared to ApoE-/- mice continuously fed either a Western diet or a normal chow diet. Collectively, we identified distinct microbiota changes accompanying atherosclerotic plaque, suggesting a future avenue for investigation on the impact of the gut microbiota, diet, and P. gingivalis infection on atherosclerosis. |
| Databáze: | OpenAIRE |
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