Lactobacillus paragasseri HM018 Derived from Breast Milk Ameliorates Hyperlipidemia in High-Cholesterol Rats by Modulating Bile Acid Metabolism

Hyperlipidemia is a prevalent metabolic disorder with rising incidence, becoming a major worldwidehealth concern. Probiotics have gained attention as mild interventions for improving hyperlipidemia.In this study, fifty specific pathogen-free Sprague-Dawley rats were randomly divided into fivegroups: normal diet, high-fat diet (HFD) model, and HFD low-dose, medium-dose, and high-doseintervention groups. After six weeks of intervention with varying concentrations of Lactobacillusparagasseri HM018, fecal samples (for microbiota analysis and non-targeted metabolomics), serumsamples (for biochemical analysis), ileum and liver tissues (for transcriptomic analysis) werecollected. The results showed that HlM018 significantly reduced the serum levels of total cholesteroltotal triglycerides, and low-density lipoproteins induced by the HFD, HM018 also ameliorated gutmicrobiota dysbiosis.'Transcriptomic analysis of the liver and ileum revealed significant upregulationof the bile acid efflux genes Abcg5 and Abcg8 and the high-density lipoprotein-related gene Apoal in the ileum after intervention, Hepatic glucose metabolism and fatty acid metabolism were alsoimproved. Metabolomic results showed that the probiotic significantly altered the composition of thefecal bile acid pool. In conclusion, HM018 may ameliorate hyperlipidemia by modulating the gutmicrobiota, regulating hepatic lipid, glucose, and bile acid metabolism, and increasing the expressionof efflux genes in the ileal tissues.