Role of Butyrate, a Gut Microbiota Derived Metabolite, in Cardiovascular Diseases: A comprehensive narrative review

Abstract

Cardiovascular diseases (CVD) are major causes of death worldwide. Recently, new roles for intestinal microbiota in pathology and treatment of CVD have been proposed. Butyrate, a bacterial metabolite, is synthesized in the gut and performs most of its functions in there. However, researchers have discovered that butyrate could enter to portal vein and interact with various organs. Butyrate exhibits a broad range of pharmacological activities, including microbiome modulator, anti-inflammatory, anti-obesity, metabolic pathways regulator, anti-angiogenesis, and antioxidant. In this article we review evidence supporting a potentially therapeutic role for butyrate in CVD and the mechanisms and pathways involved in the cardio-protective effects of butyrate from the gut and circulation to the nervous system. In summary, although butyrate exhibits a wide variety of biological activities in different pathways including energy homeostasis, glucose and lipid metabolism, inflammation, oxidative stress, neural signaling, and epigenetic modulation in experimental settings, it remains unclear whether these findings are clinically relevant and whether the molecular pathways are activated by butyrate in humans.

Keywords: antioxidant; butyrate; cardiovascular diseases; epigenetic modulation; gut microbiota.

FIGURE 1

All butyrate producing bacteria in different clostridial clusters.

FIGURE 2

An overview of butyrate’s protective effects in CVD and CVD risk factors. FFAR: free fatty acid receptor, HDAC: Histone deacetylase, KLF2: Kruppel Like Factor 2,VEGF: vascular endothelial growth factor, GLP-1: glucagon-like peptide 1, PYY, peptide YY.