Gut microbiota in atherosclerosis: focus on trimethylamine N‐oxide

Zhu, Yingqian; Li, Qingqing; Jiang, Hua

doi:10.1111/apm.13038

Cited by 125 publications

(98 citation statements)

References 119 publications

(159 reference statements)

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“…Methylglyoxal is a product of glucose and glycine metabolism that increases the activity of the gut microbial trimethylamine (TMA)-lyase [ 46 ]. TMA lyase catalyzes the transformation of dietary choline and carnitine to TMA, which in turn is metabolized by the liver to trimethylamine-N-oxide (TMAO), a potential risk factor for cardiovascular diseases [ 47 ]. The pan-genome of the Liebefeld selection covers the superpathway “methylglyoxal degradation IV” similarly to subjects MH0002 and MH0003.…”

Section: Resultsmentioning

confidence: 99%

In Silico Comparison Shows that the Pan-Genome of a Dairy-Related Bacterial Culture Collection Covers Most Reactions Annotated to Human Microbiomes

et al. 2020

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The diversity of the human microbiome is positively associated with human health. However, this diversity is endangered by Westernized dietary patterns that are characterized by a decreased nutrient variety. Diversity might potentially be improved by promoting dietary patterns rich in microbial strains. Various collections of bacterial cultures resulting from a century of dairy research are readily available worldwide, and could be exploited to contribute towards this end. We have conducted a functional in silico analysis of the metagenome of 24 strains, each representing one of the species in a bacterial culture collection composed of 626 sequenced strains, and compared the pathways potentially covered by this metagenome to the intestinal metagenome of four healthy, although overweight, humans. Remarkably, the pan-genome of the 24 strains covers 89% of the human gut microbiome’s annotated enzymatic reactions. Furthermore, the dairy microbial collection covers biological pathways, such as methylglyoxal degradation, sulfate reduction, γ-aminobutyric (GABA) acid degradation and salicylate degradation, which are differently covered among the four subjects and are involved in a range of cardiometabolic, intestinal, and neurological disorders. We conclude that microbial culture collections derived from dairy research have the genomic potential to complement and restore functional redundancy in human microbiomes.

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Section: Resultsmentioning

confidence: 99%

In Silico Comparison Shows that the Pan-Genome of a Dairy-Related Bacterial Culture Collection Covers Most Reactions Annotated to Human Microbiomes

et al. 2020

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“…A significant hallmark of atherosclerosis is the accumulation of pro-inflammatory Macs and dendritic cells (DCs) in coronary arteries that respond to pro-atherogenic stimuli, such as free fatty acids (FFAs) and oxidized LDLs (oxLDLs), and the failure to digest lipids that contribute to the formation of foam cells in atherosclerotic plaques [ 16 , 17 ]. Mechanisms that reduce Mac/DC inflammation, increase lipid degradation, and prevent foam cell formation would all decrease atherosclerosis progression.…”

Section: Microbiota-derived Metabolites Associated With Atherosclementioning

confidence: 99%

Microbiota-Mediated Immune Regulation in Atherosclerosis

et al. 2021

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There is a high level of interest in identifying metabolites of endogenously produced or dietary compounds generated by the gastrointestinal (GI) tract microbiota, and determining the functions of these metabolites in health and disease. There is a wealth of compelling evidence that the microbiota is linked with many complex chronic inflammatory diseases, including atherosclerosis. Macrophages are key target immune cells in atherosclerosis. A hallmark of atherosclerosis is the accumulation of pro-inflammatory macrophages in coronary arteries that respond to pro-atherogenic stimuli and failure of digesting lipids that contribute to foam cell formation in atherosclerotic plaques. This review illustrates the role of tryptophan-derived microbiota metabolites as an aryl hydrocarbon receptor (AhR) ligand that has immunomodulatory properties. Also, microbiota-dependent trimethylamine-N-oxide (TMAO) metabolite production is associated with a deleterious effect that promotes atherosclerosis, and metabolite indoxyl sulfate has been shown to exacerbate atherosclerosis. Our objective in this review is to discuss the role of microbiota-derived metabolites in atherosclerosis, specifically the consequences of microbiota-induced effects of innate immunity in response to atherogenic stimuli, and how specific beneficial/detrimental metabolites impact the development of atherosclerosis by regulating chronic endotoxemic and lipotoxic inflammation.

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“…TMA is a metabolic precursor that is converted to a trimethylamine N-oxide (TMAO) in the liver. TMAO drives atherosclerosis progression [110], in part, by regulating macrophage activation and foam cell formation, platelet activation, and aggregation, resulting in elevated expression of IL-1β, IL-6, and TNFα inflammatory cytokines [134]. Recent work implies that TMAO could be also involved in metabolic dysfunction and activation of inflammation, directly acting via its receptor protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) [135].…”

Section: Intestinal Microbiota In Cvd Developmentmentioning

confidence: 99%

Act Locally, Act Globally—Microbiota, Barriers, and Cytokines in Atherosclerosis

Kurilenko

Fatkhullina

Mazitova

et al. 2021

Cells

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Atherosclerosis is a lipid-driven chronic inflammatory disease that is characterized by the formation and progressive growth of atherosclerotic plaques in the wall of arteries. Atherosclerosis is a major predisposing factor for stroke and heart attack. Various immune-mediated mechanisms are implicated in the disease initiation and progression. Cytokines are key mediators of the crosstalk between innate and adaptive immune cells as well as non-hematopoietic cells in the aortic wall and are emerging players in the regulation of atherosclerosis. Progression of atherosclerosis is always associated with increased local and systemic levels of pro-inflammatory cytokines. The role of cytokines within atherosclerotic plaque has been extensively investigated; however, the cell-specific role of cytokine signaling, particularly the role of cytokines in the regulation of barrier tissues tightly associated with microbiota in the context of cardiovascular diseases has only recently come to light. Here, we summarize the knowledge about the function of cytokines at mucosal barriers and the interplay between cytokines, barriers, and microbiota and discuss their known and potential implications for atherosclerosis development.

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Gut microbiota in atherosclerosis: focus on trimethylamine N‐oxide

Cited by 125 publications

References 119 publications

In Silico Comparison Shows that the Pan-Genome of a Dairy-Related Bacterial Culture Collection Covers Most Reactions Annotated to Human Microbiomes

In Silico Comparison Shows that the Pan-Genome of a Dairy-Related Bacterial Culture Collection Covers Most Reactions Annotated to Human Microbiomes

Microbiota-Mediated Immune Regulation in Atherosclerosis

Act Locally, Act Globally—Microbiota, Barriers, and Cytokines in Atherosclerosis

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