Unraveling the environmental and genetic interactions in atherosclerosis: Central role of the gut microbiota

Abstract

Recent studies have convincingly linked gut microbiota to traits relevant to atherosclerosis, such as insulin resistance, dyslipidemia and inflammation, and have revealed novel disease pathways involving microbe-derived metabolites. These results have important implications for understanding how environmental and genetic factors act together to influence cardiovascular disease (CVD) risk. Thus, dietary constituents are not only absorbed and metabolized by the host but they also perturb the gut microbiota, which in turn influence host metabolism and inflammation. It also appears that host genetics helps to shape the gut microbiota community. Here, we discuss challenges in understanding these interactions and the role they play in CVD.

Analysis of Gut Microbiota in Coronary Artery Disease Patients: a Possible Link between Gut Microbiota and Coronary Artery Disease

“…Turnbaugh et al first demonstrated that transplanting fecal microbiota from obese mice into germ-free mice resulted in the efficient transmission of the obese phenotype into the recipients, which suggested that a change of microbiota could be a cause of the obese phenotype 12) . The association between atherosclerosis and gut microbiota has been attracting increased attention 13,14) . A recent study reported that the gut microbiota-dependent metabolite, trimethylamine N oxide (TMAO), is associated with the incidence of cardiovascular disease.…”

Gut microbiome and lipid metabolism

“…However, studies in germ-free mice have indicated that the gut microbiota affect many organs that contribute to metabolic control, including the liver, adipose tissue, and skeletal muscle [21,22,28,29]. Although the mechanisms underlying these microbial effects are largely undetermined, many studies have supported SCFAs and bile acids as important mediators [30,31]. SCFAs (acetate, butyrate, propionate) are generated by gut bacterial fermentation of dietary fibre and the role of SCFAs in host energy homeostasis and metabolism was recently intensively reviewed [32].…”

Gastrointestinal dysbiosis and the use of fecal microbial transplantation inClostridium difficileinfection

“…Additionally, the HGM plays a key role in host defense, providing a protective and competitive layer to resist growth of different patho gens. However, dysbiosis and overgrowth of microbiota has been seen in several different diseases, including inflammatory bowel disease (IBD) [9] and irritable bowel syndrome [10] , allergy and asthma [11] , tumorigenesis [12] , nonalcoholic fatty liver disease [13] , cardiovascular disea se [14] , autism [15,16] , and obesity [17,18] . It is clear that proper maintenance and turnover of the microbiota is essential for proper health.…”

“…However, the antibiotics used to treat these infections are not always specifically targeted towards the diseasecausing bacteria, as broadspectrum antibiotics can target other bacteria, including the commensal bacteria in the human intesti nal tract, known as the human gut microbiota (HGM). Furthermore, calls from various health agencies and ministries have been made for improved antibiotic stewardship, as overprescription of antibiotics has led to escalations in antibioticresistant bacteria [14] , including Clostridium difficile (C. difficile) [5] . While the increases in antibiotic resistance cannot be over looked, the indirect impact of antibiotics on the HGM is a growing problem.…”