Role and mechanism of action of butyrate in atherosclerotic diseases: a review

Abstract

Butyrate is a bioactive molecule produced by the intestinal flora and plays a major role in a variety of inflammatory diseases. Increasing evidence indicates that butyrate can regulate the occurrence and development of atherosclerosis. Coincidentally, it reduces hyperlipidemia and hyperglycemia, which are major risk factors of atherosclerosis. However, the mechanism by which butyrate regulates the development of atherosclerosis remains unclear. In this article, we review the effect of butyrate treatment on atherosclerosis with a focus on the mechanisms of butyrate-mediated modulation of several atherosclerotic processes. These include the improvement of monocyte-endothelial interactions, macrophage lipid accumulation, smooth muscle cell proliferation and migration, and lymphocyte differentiation and function. The existing research indicates that butyrate treatment may be a potentially effective strategy for the prevention of atherosclerosis. Identity and underlying mechanisms of the molecular pathways of these interactions should be explored in the future to counter atherosclerosis effectively.

Mechanistic insights into the pleiotropic effects of butyrate as a potential therapeutic agent on NAFLD management: A systematic review

“…In general, butyrate's inhibitory effect was seen in apolipoprotein B-48 output, TG export and chylomicron and VLDL secretion (79). Moreover, butyrate significantly reduced cholesterol synthesis by decreasing 3hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) levels in the liver microsomes of rats (80). It is suggested that the reverse cholesterol transport system played a significant role in atherosclerosis progression, stimulating the cholesterol movement from the peripheral tissues to the liver for re-use or excretion into the bile acid and by upregulating cytochrome P450 7A1 (81).…”

The microbiome’s relationship with congenital heart disease: more than a gut feeling

“…Butyrate is a short-chain fatty acid essential to the host immune homeostasis and a major energy source for intestinal epithelial cells [56]. The most abundant butyrate-producing organisms are Clostridium, Eubacterium, Fusobacterium, and Bifidobacterium [57][58][59]. The depletion of butyrate-producing organisms contributes to intestinal EBD and upregulated inflammatory responses in the body.…”

“…Higher F/B ratio and elevations in Enterobacteriaceae have been associated with depleted quantities of butyrate-producing organisms, increased systemic inflammation, and stroke [60]. A diet high in fiber promotes butyrate-producing organism growth and has been shown to stabilize plaque size in atherosclerosis [59]. Heart failure and coronary artery disease have also been associated with a reduction in butyrate-producing organisms [59,61].…”

“…A diet high in fiber promotes butyrate-producing organism growth and has been shown to stabilize plaque size in atherosclerosis [59]. Heart failure and coronary artery disease have also been associated with a reduction in butyrate-producing organisms [59,61].…”

“…Butyrate is responsible for maintaining the intestinal barrier through modulation of G-coupled proteins and transcription factors, namely the nuclear transcription factor-κB (NF-κB) pathway, to upregulate regulatory T-cells. Loss of butyrate producing organisms can lead to EBD resulting in passive leak of lipopolysaccharides and other microbial toxins, which then bind to toll-like receptors on T cells activating the innate immune response [59,61,80,81]. A third mechanism involves elevated TMAO production leading to EBD and activated inflammatory processes causing further cardiac injury [81][82][83].…”