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Thyme (Thymus quinquecostatus Celak) is a plant commonly used in cuisine and traditional medicine in Asian countries and possesses potential liver-protective properties. This study aimed to assess the hepatoprotective effects of thyme polyphenol-rich extract (TPE) on high-fat diet (HFD)-induced NAFLD and further explore possible mechanisms based on the gut\u2013liver axis. HFD-induced liver injury in C57 mice is markedly ameliorated by TPE supplementation in a dose-dependent manner. TPE also regulates the expression of liver lipid metabolic genes (i.e., Hmgcr, Srebp-1, Fasn, and Cyp7a1), enhancing the production of SCFAs and regulating serum metabolites by modulating gut microbial dysbiosis. Furthermore, TPE enhances the intestinal barrier function and alleviates intestinal inflammation by upregulating tight junction protein expression (i.e., ZO-1 and occluding) and inactivating the intestinal TLR4\/NF-\u03baB pathway in HFD-fed mice. Consequently, gut-derived LPS translocation to the circulation was blocked, the liver TLR4\/NF-\u03baB signaling pathway was repressed, and subsequent pro-inflammatory cytokine production was restrained. Conclusively, TPE might exert anti-NAFLD effects through the gut\u2013liver axis and has the potential to be used as a dietary supplement for the management of NAFLD.<\/jats:p>","DOI":"10.3390\/foods12163074","type":"journal-article","created":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T10:08:09Z","timestamp":1692180489000},"page":"3074","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Thyme (Thymus quinquecostatus Celak) Polyphenol-Rich Extract (TPE) Alleviates HFD-Induced Liver Injury in Mice by Inactivating the TLR4\/NF-\u03baB Signaling Pathway through the Gut\u2013Liver Axis"],"prefix":"10.3390","volume":"12","author":[{"given":"Xialu","family":"Sheng","sequence":"first","affiliation":[{"name":"College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Food Engineering, Shaanxi Xueqian Normal University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhan","sequence":"additional","affiliation":[{"name":"College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanying","family":"He","sequence":"additional","affiliation":[{"name":"College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglei","family":"Tian","sequence":"additional","affiliation":[{"name":"College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianshu","family":"Liu","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial Research Center of Functional Food Engineering Technology, Xi\u2019an 710100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1056\/NEJMra1503519","article-title":"Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis","volume":"377","author":"Diehl","year":"2017","journal-title":"NEJM"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S2468-1253(22)00165-0","article-title":"The prevalence and incidence of NAFLD worldwide: A systematic review and meta-analysis","volume":"7","author":"Riazi","year":"2022","journal-title":"Lancet Gastroenterol. 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