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Until now, systematic studies on the amelioration of hypercholesterolemia have been rare in terms of (cholesterol metabolism and transportation, reshaping of gut microbiota, as well as yielding SCFAs) intervention with lactic acid bacteria (LAB). In this study, strains of Lactiplantibacillus plantarum, WLPL21, WLPL72, and ZDY04, from fermented food and two combinations (Enterococcus faecium WEFA23 with L. plantarum WLPL21 and WLPL72) were compared for their effect on hypercholesterolemia. Comprehensively, with regard to the above aspects, L. plantarum WLPL21 showed the best mitigatory effect among all groups, which was revealed by decreasing total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, upregulated cholesterol metabolism (Cyp27a1, Cyp7b1, Cyp7a1, and Cyp8b1) levels in the liver, cholesterol transportation (Abca1, Abcg5, and Abcg8) in the ileum or liver, and downregulated Npc1l1. Moreover, it reshaped the constitution of gut microbiota; specifically, the ratio of Firmicutes to Bacteroidetes (F\/B) was downregulated; the relative abundance of Allobaculum, Blautia, and Lactobacillus was upregulated by 7.48\u201314.82-fold; and that of Lachnoclostridium and Desulfovibrio was then downregulated by 69.95% and 60.66%, respectively. In conclusion, L. plantarum WLPL21 improved cholesterol metabolism and transportation, as well as the abundance of gut microbiota, for alleviating high-cholesterol-diet-induced hypercholesterolemia.<\/jats:p>","DOI":"10.3390\/nu15112600","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T01:33:54Z","timestamp":1685669634000},"page":"2600","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Alleviation Syndrome of High-Cholesterol-Diet-Induced Hypercholesterolemia in Mice by Intervention with Lactiplantibacillus\u00a0plantarum WLPL21 via Regulation of Cholesterol Metabolism and Transportation as Well as Gut Microbiota"],"prefix":"10.3390","volume":"15","author":[{"given":"Kui","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Qiu","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330047, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"Tao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.5551\/jat.49098","article-title":"Hypercholesterolemia and Lifetime Risk of Coronary Heart Disease in the General Japanese Population: Results from the Suita Cohort Study","volume":"27","author":"Sugiyama","year":"2020","journal-title":"J. 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