Unraveling Host-Gut Microbiota Dialogue and Its Impact on Cholesterol Levels

Abstract

Disruption in cholesterol metabolism, particularly hypercholesterolemia, is a significant cause of atherosclerotic cardiovascular disease. Large interindividual variations in plasma cholesterol levels are traditionally related to genetic factors, and the remaining portion of their variance is accredited to environmental factors. In recent years, the essential role played by intestinal microbiota in human health and diseases has emerged. The gut microbiota is currently viewed as a fundamental regulator of host metabolism and of innate and adaptive immunity. Its bacterial composition but also the synthesis of multiple molecules resulting from bacterial metabolism vary according to diet, antibiotics, drugs used, and exposure to pollutants and infectious agents. Microbiota modifications induced by recent changes in the human environment thus seem to be a major factor in the current epidemic of metabolic/inflammatory diseases (diabetes mellitus, liver diseases, inflammatory bowel disease, obesity, and dyslipidemia). Epidemiological and preclinical studies report associations between bacterial communities and cholesterolemia. However, such an association remains poorly investigated and characterized. The objectives of this review are to present the current knowledge on and potential mechanisms underlying the host-microbiota dialogue for a better understanding of the contribution of microbial communities to the regulation of cholesterol homeostasis.

Keywords: LDL-cholesterol; cholesterol; cholesterolemia; dyslipidemia and cardiovascular disease; gut metabolites; gut microbiota; microbiome.

Figure 1

Schematic view of host-gut microbial co-metabolism of bile acids and cholesterol in enterohepatic circulation.

Figure 2

Schematic depicting the range of putative pathways through which the gut metabolites impact on cholesterol metabolism. Diet nutriments (green boxes) are metabolized and transformed into microbial metabolites (blue boxes) by gut microbiota. Purple boxes represent enzymes. Red boxes represent host metabolites. TMA, Trimethylamine; TMA-O, Trimethylamine-Oxide; SCFAs, Short Chain Fatty Acids; BAs, Bile Acids; IAA, Indole-3-acetic acid; IPA, Indole-3-propionic acid; IDO, indoleamine2,3-dioxygenase; 3-HAA, 3-hydroxyanthranilic; LPS, lipopolysaccharides.