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It is a significant risk factor for a range of cardiovascular diseases, including acute pancreatitis, fatty liver disease, atherosclerosis, and coronary heart disease. In clinical practice, the management of hyperlipidemia is hindered by numerous challenges. One of the critical issues is that traditional lipid-lowering drugs often require long-term or even lifelong administration, potentially inducing a range of adverse effects that compromise patient compliance and therapeutic efficacy. Therefore, there is an urgent need to develop safer and more effective strategies for the prevention and adjunctive treatment of hyperlipidemia with the aim of reducing the risk of disease and over-reliance on medication. Recent studies have revealed a close relationship between hyperlipidemia and related metabolic disorders involving gut microbiota dysbiosis, and the administration of probiotics has been shown to improve lipid metabolism homeostasis. This review summarizes the molecular mechanisms of probiotics in hyperlipidemia treatment and the latest advances in probiotic research on lipid metabolism, enumerates the experimental and clinical applications of probiotic-based therapies, introduces methods for screening and identifying probiotics with lipid-lowering functions, and, for the first time, summarizes the roles of emerging technologies such as functional genomics and in vivo zebrafish-on-a-chip models in studying the lipid-lowering efficacy of probiotics, providing insights for researchers. By facilitating a deeper understanding of the mechanisms whereby probiotics reduce blood lipid levels and furthering the development of multifaceted screening methods, we hope that we can achieve high-throughput and efficient screening of probiotics with lipid-lowering functions, thereby promoting the sustainable, high-quality, and rapid development of the probiotics industry.<\/jats:p>","DOI":"10.3390\/foods14091583","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T06:49:02Z","timestamp":1746082142000},"page":"1583","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Research Progress on the Mechanism of Action and Screening Methods of Probiotics for Lowering Blood Lipid Levels"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3856-5226","authenticated-orcid":false,"given":"Jingli","family":"Wang","sequence":"first","affiliation":[{"name":"School of Food and Drug, Shenzhen Polytechnic University, Shenzhen 518055, China"},{"name":"School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieyu","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Food and Drug, Shenzhen Polytechnic University, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingkun","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Food and Drug, Shenzhen Polytechnic University, Shenzhen 518055, China"},{"name":"School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijun","family":"Ouyang","sequence":"additional","affiliation":[{"name":"School of Food and Drug, Shenzhen Polytechnic University, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhui","family":"Li","sequence":"additional","affiliation":[{"name":"School of Food and Drug, Shenzhen Polytechnic University, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1730-7298","authenticated-orcid":false,"given":"Dong","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Food and Drug, Shenzhen Polytechnic University, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5607-6122","authenticated-orcid":false,"given":"Mingjun","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Food and Drug, Shenzhen Polytechnic University, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/s41569-021-00541-4","article-title":"Global epidemiology of dyslipidaemias","volume":"18","author":"Pirillo","year":"2021","journal-title":"Nat. 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