Background

Hyperlipidemia involves an imbalance of cholesterol levels, including low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in the blood. LDL-C and HDL-C regulate the amount of cholesterol in the body and an imbalance can increase the risk of cardiovascular events, including myocardial infarction and stroke. Other forms of hyperlipidemia include hypertriglyceridemia as well as mixed hyperlipidemia, in which both cholesterol and triglyceride levels are elevated. Elevated LDL-C can lead to a buildup of plaques within the arteries and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease or stroke. As HDL-C functions to remove cholesterol from the body, increased levels of HDL-C (≥60 mg/dL) can help decrease the risk of ASCVD[1].

We personally conducted an investigation at the First Hospital of Lanzhou University and interviewed experts from the Gansu Provincial Center for Disease Control and Prevention to clarify the trend of increasing incidence of hypercholesterolemia in Gansu province. In the United States, more than 100 million, or roughly 53% of adults, have elevated LDL-C levels[2]. Yet, fewer than 50% of patients with high LDL-C receive treatment to reduce their levels, and among those receiving treatment, fewer than 35% achieve adequate control[2,3]. Further, approximately 31 million American adults have total cholesterol levels that exceed 240 mg/dL, placing them at about twice the risk of ASCVD compared to those with total cholesterol levels that are at goal[4].

The association between obesity and the gut microbiome suggests that bacteria in particular influence host lipid metabolism and hence atherosclerosis. In a study of over 800 subjects, it was shown that the gut flora played a significant role in the variation of blood lipids. Increased lipids in the blood were associated with the loss of commensal bacteria such as Bacteroidetes and Clostridia[5]. Functional analyses of the microbiome in patients with atherosclerosis further suggest an increased capacity to metabolize certain lipids[6]. Utilizing the gut microbiota to control cholesterol levels in the human body would be a novel strategy for the prevention and treatment of hypercholesterolemia and even atherosclerosis.

[1] Cooney MT, Dudina A, De Bacquer D, et al. HDL cholesterol protects against cardiovascular disease in both genders, at all ages and at all levels of risk. Atherosclerosis. 2009;206(2):611-616. doi: 10.1016/j.atherosclerosis.2009.02.041.
[2] Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 2016;133(4):e38-e360. doi: 10.1161/CIR.0000000000000350.
[3] Centers for Disease Control and Prevention (CDC). Vital signs: prevalence, treatment, and control of high levels of low-density lipoprotein cholesterol—United States, 1999-2002 and 2005-2008. MMWR Morb Mortal Wkly Rep. 2011;60(4):109-114.
[4] Nussbaumerová B, Rosolová H. Epidemiologie hypercholesterolemie [Epidemiology of hypercholesterolemia]. Vnitr Lek. 2018 Winter;64(1):30-37. Czech. PMID: 29498873.
[5] Fu J, Bonder MJ, Cenit MC, Tigchelaar EF, Maatman A, Dekens JA, Brandsma E, Marczynska J, Imhann F, Weersma RK, Franke L, Poon TW, Xavier RJ, Gevers D, Hofker MH, Wijmenga C, Zhernakova A. The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids. Circ Res. 2015 Oct 9;117(9):817-24. doi: 10.1161/CIRCRESAHA.115.306807. Epub 2015 Sep 10. PMID: 26358192; PMCID: PMC4596485.
[6] Jie Z, Xia H, Zhong SL, Feng Q, Li S, Liang S, Zhong H, Liu Z, Gao Y, Zhao H, Zhang D, Su Z, Fang Z, Lan Z, Li J, Xiao L, Li J, Li R, Li X, Li F, Ren H, Huang Y, Peng Y, Li G, Wen B, Dong B, Chen JY, Geng QS, Zhang ZW, Yang H, Wang J, Wang J, Zhang X, Madsen L, Brix S, Ning G, Xu X, Liu X, Hou Y, Jia H, He K, Kristiansen K. The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun. 2017 Oct 10;8(1):845. doi: 10.1038/s41467-017-00900-1. PMID: 29018189; PMCID: PMC5635030.