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Emerging evidence has shown that the gut microbiota may play an important role in cholesterol metabolism. In this review, we delve into five possible mechanisms by which the gut microbiota may influence cholesterol metabolism: (1) the gut microbiota changes the ratio of free bile acids to conjugated bile acids, with the former being eliminated into feces and the latter being reabsorbed back into the liver; (2) the gut microbiota can ferment dietary fiber to produce short-chain fatty acids (SCFAs) which are absorbed and reach the liver where SCFAs inhibit cholesterol synthesis; (3) the gut microbiota can regulate the expression of some genes related to cholesterol metabolism through their metabolites; (4) the gut microbiota can convert cholesterol to coprostanol, with the latter having a very low absorption rate; and (5) the gut microbiota could reduce blood cholesterol by inhibiting the production of lipopolysaccharides (LPS), which increases cholesterol synthesis and raises blood cholesterol. In addition, this review will explore the natural constituents in foods with potential roles in cholesterol regulation, mainly through their interactions with the gut microbiota. These include polysaccharides, polyphenolic entities, polyunsaturated fatty acids, phytosterols, and dicaffeoylquinic acid. These findings will provide a scientific foundation for targeting hypercholesterolemia and cardiovascular diseases through the modulation of the gut microbiota.<\/jats:p>","DOI":"10.3390\/foods12234308","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T03:53:52Z","timestamp":1701230032000},"page":"4308","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Effect of Gut Microbiota on Blood Cholesterol: A Review on Mechanisms"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8751-4518","authenticated-orcid":false,"given":"Chuanling","family":"Deng","sequence":"first","affiliation":[{"name":"School of Food Science and Engineering\/National Technical Center (Foshan) for Quality Control of Famous and Special Agricultural Products (CAQS-GAP-KZZX043), Foshan University, Foshan 528011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjin","family":"Pan","sequence":"additional","affiliation":[{"name":"School of Food Science and Engineering\/National Technical Center (Foshan) for Quality Control of Famous and Special Agricultural Products (CAQS-GAP-KZZX043), Foshan University, Foshan 528011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyue","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Food Science and Engineering\/National Technical Center (Foshan) for Quality Control of Famous and Special Agricultural Products (CAQS-GAP-KZZX043), Foshan University, Foshan 528011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5615-1682","authenticated-orcid":false,"given":"Zhen-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Life Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1152\/physrev.00045.2009","article-title":"Gut Microbiota in Health and Disease","volume":"90","author":"Sekirov","year":"2010","journal-title":"Physiol. 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