Probiotic strains improve high-fat diet-induced hypercholesterolemia through modulating gut microbiota in ways different from atorvastatin

Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD). Probiotics is one of the most popular dietary supplements for hypercholesterolemia, but there are questions as to whether there are differences between probiotics and cholesterol-lowering drugs as like atorvastatin (ATO) both in effectiveness and the underlying mechanisms. In this study, the hypocholesterolemia effects of 4 probiotic strains were investigated and compared with ATO, focusing on their impacts on gut microbiota. Hypercholesterolemia model was established via high-fat diet (HFD) in golden hamsters after which ATO and the 4 probiotics were orally administered individually for 8 weeks. All probiotics were effective, but less than ATO, both on body weight, serum parameters (TG, TC, LDL, INS, HbA1c) and expression of inflammatory factors (TNF-α, IL-1β, CRP), with strain JQII-5 most significant. Besides, these effects were associated with restoration of the microbiota dysbiosis induced by HFD. It was worth noting that ATO and probiotics induced different shifts of gut microbiota in both structure and key phylotypes. Most interestingly, Allobaculum, a HFD-suppressed genus, reported to be involved in alleviating oxidative stress, was enriched by all tested probiotic strains, but not by ATO. Furthermore, Prevotella, also a HFD-suppressed genus, was uniquely reversed by JQII-5. Importantly, most of the alerted genus and reversed genus was found to be correlated to inflammatory state and serum lipid level. Compared with ATO, probiotic strains were less effective on body weight, hypercholesterolemia, and inflammation. However, probiotics exert additional favorable effects on gut microbiota, making them excellent potential complements to cholesterol-lowering drugs like ATO.