Abstract

The new dimension in cardio-metabolic health: Cardio-metabolic disorders (CMDs) encompass various disorders like metabolic syndrome, obesity, diabetes and cardiovascular disease (CVD) including atherosclerosis, hypertension, coronary artery diseases, cerebrovascular disease and heart failure. CMD occur due to insulin resistance (IR), inflammation, deranged energy and metabolic homeostasis. Apart from various predisposing factors including genetic and environmental and lifestyle factors, the novel factors such as nutritional and gut microbial dysbiosis have also been implicated for CMDs.

Microbial dysbiosis and metabolic disorders: Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome and related diseases. The impairment of the fine balance between gut microbes and host’s immune system culminates into intestinal microbial dysbiosis and development of metabolic endotoxemia, leading to systemic inflammation and IR. There has been outlined the gut microbiota-dependent mechanisms linking the gut microbial dysbiosis and the development of metabolic disorders like insulin resistance, diabetes, obesity and non-alcoholic fatty liver disease (NAFLD).

Microbial dysbiosis and atherosclerosis: The recent clinical and animal studies have documented that gut dysbiosis contributes to the development of atherosclerosis through modulation of various pathways. There is evidence that gut microbiota plays a causative role in atherosclerosis by modulating inflammation through production of microbial metabolites like short-chain fatty acids (SCFAs). The secondary bile acids are another group of gut microbiota-derived metabolite involved in CVD and various metabolic diseases.

Microbial dysbiosis and hypertension: Apart from, dyslipidemia, hypertension is another most important risk factor for CVD that bears genetic susceptibility and influenced by environmental factors. The gut dysbiosis has been linked with cerebrovascular events apart from metabolic disorders. Simultaneously, there exists a relationship between gut microbiota and hypertension, which has been established by various recent studies. Both SCFAs and oxidized LDL have been associated with the microbiota-linked mechanisms for development or exacerbation of hypertension.

Microbiota-targeted therapy for CMD: The gut microbiota is a novel therapeutic target for the treatment of CMD. Over the recent years, there have evolved potential strategies for therapeutically targeting intestinal microbiota and microbial processes. The MTT appears to be a promising strategy to prevent and treat metabolic disorders as well as CVD. The most frequently used measures to manipulate the gut microbiota to reduce CV risk and CVD are therapeutic use of probiotics, prebiotics and certain nutraceuticals. The therapeutic intervention to repair microbial dysbiosis through fecal microbiota transplantation (FMT) appears to be a potential therapy for CVD and various metabolic disorders like metabolic syndrome, T2DM and obesity.

Keywords: Atherosclerosis; Dysbiosis; FMT; Hypertension; Insulin resistance; Metabolic syndrome; Microbiota; Microbiota-targeted therapy; NAFLD, Obesity; Prebiotics; Probiotics; Resveratrol