Hyperlipidemia and gut microbiota: the role of prebiotics, probiotics, statins and fibrates

Aim of the study was to characterize the intestinal microbiota and its metabolites in hyperlipidemia and analyze the associations between the intestinal microbiota and some biological (prebiotics and probiotics) and lipid-lowering (statins, fibrates) drugs in the treatment of hyperlipidemia. In hyperlipidemia, the number of bacteria producing toxic metabolites such as lipopolysaccharide and trimethylamine-N-oxide (TMAO) is increased (Bacillota (former Firmicutes), Pseudomonadota (former Proteobacteria), Desulfovibrionaceae) and the number of intestinal producers of beneficial short-chain fatty acids and bile salt hydrolase is decreased (Bacteroidota (former Bacteroidetes), Verrucomicrobia, Bifidobacterium, Lactobacillus, Streptococcus, Eubacterium). Prebiotics can improve lipid metabolism, but the mechanisms of such effect remain unknown. Probiotics (the best studied are Lactobacillus and Bifidobacterium) can remove cholesterol from circulation (by adsorbing and assimilating it on cell membranes), reduce intestinal absorption of cholesterol (by stimulating de novo bile acid synthesis), and modulate cholesterol synthesis (by inhibiting HMG-CoA reductase and reducing the expression of the ATP-associated cassette transporter type A1 gene family). Lactobacillus, in addition to improving the intestinal microbial profile and lipid metabolism, reduces body weight, blood pressure, inflammation, and insulin resistance. Statins and the intestinal microbiota demonstrate mutual influence: a better response to statin treatment is associated with a higher diversity of microbiota, statins are also able to restore the microbiota altered due to pathology to a healthier state (reduce the number of potential pathogens, such as Parabacteroides merdae, and increase the number of beneficial bacteria – Bifidobacterium longum, Bifidobacterium bifidum, Anaerostipes hadrus, Faecalibacterium prausnitzii, Akkermansia muciniphila and the genus Oscillospira, and reduce plasma TMAO levels). Moreover, the effect of statins on the composition and function of the gut microbiota does not depend on a decrease in cholesterol level. The data on the effects of fibrates on the microbiota, studied in mice, are contradictory: in some studies, fenofibrate can reduce caused by a high-fat diet systemic inflammation and lipid metabolism disorders, while in others, on the contrary, it can increase obesity and inflammation. Conclusions. The gut microbiome opens up fundamentally new approaches to the treatment of cardiometabolic diseases in the era of precision medicine.