Table 2.
Summary of important studies.
| Reference | Model | Aim of Study | Experiment Design | Main Finding |
|---|---|---|---|---|
| [24] | Human Mouse |
Gut flora-dependent metabolism of dietary phosphatidylcholine on CVD pathogenesis | Metabolomics approach in human cohort Choline isotope tracer feeding in mice |
Dietary supplementation with choline or TMAO promoted upregulation of macrophage scavenger receptors linked to atherosclerosis, and aggravated atherosclerosis |
| [25] | Human Mouse |
Role of gut microbiota on TMAO production from dietary L-carnitine and relationship of TMAO and CVD risk | Metabolomics approach Human/mouse microbiota analyses Isotopic L-carnitine feeding in mice |
L-carnitine supplementation significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis |
| [29] | Human Mouse Microorganism |
Identifying novel pathways linked to CVD | Metabolomics approach in CVD vs. non-CVD patients In vivo FeCl3-induced thrombosis model |
PAGln represents a new CVD-promoting gut microbiota-dependent metabolite that signals via adrenergic receptors |
| [55] | Mouse | Mechanism of HDL promoting regression of atherosclerosis | Aortic transplantation Lipid and Lipoprotein Analyses |
HDL as a regulator of the migration and inflammation of monocyte-derived cells in murine atherosclerotic plaques |
| [59] | Mouse | Effect of simvastatin on macrophages and plaque regression | Nanoparticle-based delivery of simvastatin in mice with advanced atherosclerotic plaques | Pharmacologically inhibiting local macrophage proliferation can effectively treat inflammation in atherosclerosis |
| [71] | Human | Feasibility of reducing inflammation to decrease the risk of CVD clinically | Canakinumab 150mg every 3 months, randomized controlled and double blind trial | Antiinflammatory therapy targeting the IL-1β led to a significantly lower rate of recurrent cardiovascular events |
| [79] | Mouse | Role of RegIIIγ on the bacterial colonization of the mucosal surface |
RegIIIγ−/− and Myd88−/− vs. wild-type littermate FISH analysis for spatial relationships between the microbiota and the host mucosal surface |
RegIIIγ is a fundamental immune mechanism that promotes host-bacterial mutualism by regulating the spatial relationships between microbiota and host |
| [106] | Mouse | Role of IL-23 on atherosclerosis | Bone marrow deletion of IL-23 FMT |
The IL-23-IL-22 signaling as a regulator of atherosclerosis that restrains expansion of pro-atherogenic microbiota |
| [134] | Mouse | Impact of microbiota from Casp1−/− mice on atherogenesis in Ldlr−/− mice | FMT from Casp1−/− mice to Ldlr−/− mice following antibiotics treatment | FMT of proinflammatory Casp1−/− microbiota into Ldlr−/− mice enhances systemic inflammation and accelerates atherogenesis |
| [142] | Mouse | Role of Akkermansia muciniphila in the pathogenesis of atherosclerosis | ApoE−/− mice treated with A. muciniphila by daily oral gavage | A. muciniphila attenuates atherosclerotic lesions by ameliorating metabolic endotoxemia-induced inflammation through restoration of the gut barrier |
| [173] | Human Mouse |
Role of TMAO on platelet activity and thrombosis | In vivo FeCl3-induced thrombosis model Metagenomic analyses by sequencing 16S ribosomal RNA in cecal microbiota FMT Platelet activity from human samples |
Gut microbes, via generation of TMAO, can directly modulate platelet hyperresponsiveness and clot formation rate in vivo |
| [178] | Mouse | Effect of butyrate-producing bacteria on atherosclerosis | FMT of either low or high butyrate-producing human microbiota to GF mice | Colonization with butyrate producing R. intestinalis decreases levels of inflammatory markers and atherosclerosis in a diet-dependent manner |
| [205] | Mouse | Effect of gut microbial transplantation from high to low TMAO-producing mice on atherosclerosis susceptibility | FMT from high to low TMAO-producing mice | Atherosclerosis susceptibility may be transmitted via transplantation of gut microbiota |
CVD: cardiovascular disease, FISH: fluorescence in situ hybridization, FMT: fecal microbial transplantation, GF: germ-free, HDL: high-density lipoprotein, LDLR: low-density lipoprotein receptor, PAGln: phenylacetylglutamine, TMAO: trimethylamine N-oxide.