Abstract
Aims: The current study investigates the role of diet in mediating the gut microbiome-cardiovascular association which has not yet been explored in humans.Methods and Results: Using a two-arm dietary intervention study in healthy participants (N = 70), we assessed the effects of omega-3 and fibre supplementation on gut microbiome composition and short-chain fatty acid (SCFA) production. We then investigated how changes in gut microbiome composition correlated with changes in traditional cardiovascular risk factors (cholesterol, triglycerides, blood pressure), cytokines, and novel validated markers such as GlycA and ceramides, previously linked to CVD incidence and mortality. Both interventions resulted in significant drops in blood pressure, cholesterol, proinflammatory cytokines, GlycA and ceramides (all P < 0.05). Decreases in the atherogenic low-density lipoprotein triglyceride fraction, in total serum cholesterol were correlated with increases in butyric acid-production [β(SE) = −0.58 (0.06), P < 0.001; −0.53 (0.04), P < 0.001] and nominally associated with increases in some butyrogenic bacteria. Drops in GlycA were linked to increases in Bifidobacterium [β(SE) = −0.32 (0.04), P = 0.02] and other SCFAs including acetic acid [β(SE) = −0.28 (0.04), P = 0.02] and propionic acid [β(SE) = −0.3 (0.04), P = 0.02]. Additionally, we report for the first-time reductions in specific ceramide ratios that have been shown to predict CVD mortality and major adverse cardiovascular events such as d18:1/16:0, d18:0/24:0, and d18:1/24:1 which were associated with the reduction in the abundance in Colinsella and increases in Bifidobacteriuim and Coprococcus 3 and SCFAs (all P < 0.05).Conclusion: Overall, these findings support the potential of using simple dietary interventions to alter validated biomarkers linked to cardiovascular risk via the gut microbiome composition and its metabolic functions.
Highlights
Cardiovascular diseases (CVDs) remain the main cause of mortality in most Western countries [1, 2]
We first investigated whether 6-weeks dietary supplementations had an effect on CVD risk factors
We explored these effects by formal mediation where short-chain fatty acids (SCFAs) were fitted as mediator of the effect of gut microbiome composition on CVD markers
Summary
Cardiovascular diseases (CVDs) remain the main cause of mortality in most Western countries [1, 2]. Other traditional risk factors for CVD include elevated body mass index, high blood pressure, smoking, increased low-density lipoprotein (LDL) and cholesterol levels, many of which have been associated to the gut microbiome [8]. Multiple lines of evidence support the association of plasma ceramide levels with adverse cardiovascular outcomes and mortality in patients with prior CVD [10, 13, 14]. GlycA, on the other hand [15] and has been shown to be associated with incident CVD, incident and prevalent type 2 diabetes, suggesting that GlycA may serve as a useful biomarker for assessment of cardiovascular disease risk as well as risk of progression to Type 2 diabetes (T2D) [16,17,18]
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