Microbiota, a New Playground for the Omega-3 Polyunsaturated Fatty Acids in Cardiovascular Diseases

Abstract

Several cardioprotective mechanisms attributed to Omega-3 polyunsaturated fatty acids (PUFAs) have been studied and widely documented. However, in recent years, studies have supported the concept that the intestinal microbiota can play a much larger role than we had anticipated. Microbiota could contribute to several pathologies, including cardiovascular diseases. Indeed, an imbalance in the microbiota has often been reported in patients with cardiovascular disease and produces low-level inflammation. This inflammation contributes to, more or less, long-term development of cardiovascular diseases. It can also worsen the symptoms and the consequences of these pathologies. According to some studies, omega-3 PUFAs in the diet could restore this imbalance and mitigate its harmful effects on cardiovascular diseases. Many mechanisms are involved and included: (1) a reduction of bacteria producing trimethylamine (TMA); (2) an increase in bacteria producing butyrate, which has anti-inflammatory properties; and (3) a decrease in the production of pro-inflammatory cytokines. Additionally, omega-3 PUFAs would help maintain better integrity in the intestinal barrier, thereby preventing the translocation of intestinal contents into circulation. This review will summarize the effects of omega-3 PUFAs on gut micro-biota and the potential impact on cardiac health.

Essential Fatty Acids as Biomedicines in Cardiac Health

“…The coupled complex of TAB-1and TAK-1 is a merging point for stimuli induced by the toll-like receptor 4 (TLR4) signaling pathway, including tumor necrosis factor receptor (TNFr) [17,18]. Similarly, a possible cardioprotective mechanism may be attributed to the activation of protein kinases B such as AKT, previously recognized as interplaying with biochemical pathways known as reperfusion injury salvage kinase (RISK) [19]. When the onset of reperfusion is initiated, these kinases bestow cardio-protective effects via mitochondrial permeability transition pore (mPTP) opening suppression.…”

“…Another possible mechanism for how dietary ω-3 PUFA might mitigate the adverse effects of cardiovascular diseases arose with their potentiality to decrease the abundance of gut bacteria producing trimethylamine (TMA), a precursor of trimethylamine-N-oxide (TMAO), and which was previously reported in atherosclerotic plaque formation [14,19].…”

“…The suppression of atherosclerotic plaques by DHA and EPA also occurs via the decline of macrophages in atherosclerotic plaque, reductions of the atherosclerotic plaque's total volume ratio, and the reduced production of platelet-derived growth factor (PDGF) responsible for chemo-attractive effects and mitogen for macrophages and smooth muscle cells [2]. Studies have suggested that TMAO can be regarded as a predictor of mortality associated with heart failure, because of the nexus that promotes the initiation of proinflammatory cytokines (TNFα, IL-6, and IL-1β), activates NOD-, LRR-, NF-κB, pyrin domain-containing protein 3 (NLRP-3) inflammasome, as well as facilitates apoptosis [19]. Within the gut, a 14-day ω-3 PUFAs supplementation (600 mg/day) [31] raised the number of butyrate-producing bacteria with anti-inflammatory capacity [32], thus supporting strengthened intestinal barrier integrity, which subsequently prevents the transasation of intestinal content into the circulation [19].…”

“…Studies have suggested that TMAO can be regarded as a predictor of mortality associated with heart failure, because of the nexus that promotes the initiation of proinflammatory cytokines (TNFα, IL-6, and IL-1β), activates NOD-, LRR-, NF-κB, pyrin domain-containing protein 3 (NLRP-3) inflammasome, as well as facilitates apoptosis [19]. Within the gut, a 14-day ω-3 PUFAs supplementation (600 mg/day) [31] raised the number of butyrate-producing bacteria with anti-inflammatory capacity [32], thus supporting strengthened intestinal barrier integrity, which subsequently prevents the transasation of intestinal content into the circulation [19]. It is indeed clear that the gut microbiota suffers negative changes in patients with diabetes or in obese patients, leading to reduced TMAO [33,34] levels, and making a clear connection between these changes and major cardiac events, such as myocardial infarction [35,36].…”

Marine Natural Products and Coronary Artery Disease

“…Emerging evidence indicates that ω3PUFAs can influence enteric microorganisms to protect the cardiovascular system by inhibiting the TMA produced by bacteria, promoting anti-inflammatory-active bacteria to create butyrate and downregulating proinflammatory fingers. In addition, ω3PUFAs defend gut barrier integrity to hold back intestinal contents from circulation ( 93 ). However, it was also reported that ω6PUFAs at high concentrations might reduce the influence of ω3PUFAs on the cardiovascular system ( 94 ).…”