Ginger essential oil and citral ameliorates atherosclerosis in ApoE−/− mice by modulating trimethylamine-N-oxide and gut microbiota Original paper

What was studied?

This study investigated the therapeutic effects and mechanisms of ginger essential oil (GEO) and its active compound, citral, on atherosclerosis progression through modulation of gut microbiota and trimethylamine-N-oxide (TMAO) production. Specifically, the research focused on evaluating how GEO and citral supplementation affected the formation of atherosclerotic plaques, plasma lipid profiles, inflammation markers, glucose and insulin metabolism, and gut microbiota composition in ApoE−/− mice. The mice were fed a high-fat, high-cholesterol Gubra Amylin NASH (GAN) diet supplemented with L-carnitine to induce atherosclerosis.

Who was studied?

The study used female ApoE−/− mice, a genetically engineered model that develops severe hypercholesterolemia and spontaneous atherosclerosis, mirroring cardiovascular disease (CVD) in humans. These mice were subjected to a GAN diet rich in cholesterol, fats, and fructose combined with L-carnitine, which enhanced atherosclerotic plaque formation through elevated production of the pro-atherogenic metabolite, TMAO. The mice were divided into control and experimental groups receiving either a low dose or high dose of GEO or citral daily for 16 weeks.

What were the most important findings?

Significant findings from this study included the ability of both GEO and citral to inhibit the formation of atherosclerotic lesions, reduce plasma levels of cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides, and significantly elevate beneficial high-density lipoprotein cholesterol (HDL-C). GEO and citral effectively reduced plasma levels of TMAO, a known risk factor for CVD, produced via gut microbiota metabolism of dietary L-carnitine. Additionally, GEO and citral treatments improved insulin sensitivity, reduced fasting blood glucose levels, and lowered plasma inflammatory markers such as IL-1β, TNF-α, and IL-6. These anti-atherosclerotic effects correlated with positive modifications in gut microbiota composition; GEO and citral increased beneficial genera such as Akkermansia, Allobaculum, and Dubosiella, while suppressing potentially pathogenic bacteria associated with elevated TMAO production, notably Enterorhabdus, Proteus, and Escherichia-Shigella. Thus, the study provided clear microbial signatures linked with the beneficial outcomes of GEO and citral supplementation.

What are the greatest implications of this study?

The greatest implication of this research is the potential for GEO and citral as dietary interventions or adjunctive therapies to prevent or mitigate cardiovascular disease through gut microbiome modulation. By reducing pathogenic gut microbiota, suppressing the formation of harmful metabolites like TMAO, and significantly improving lipid profiles and inflammation markers, these compounds represent promising candidates for natural, microbiome-targeted preventive strategies in cardiovascular disease management. This insight underscores the value of dietary essential oils in clinical practice and highlights gut microbiome modulation as a significant therapeutic target for atherosclerosis and associated metabolic disorders.