Oleuropein Regulates Bile Acid Metabolism via Modulating the Gut Microbiota, Thereby Alleviating DSS-Induced Ulcerative Colitis in Mice

The pathogenesis of ulcerative colitis (UC) involves genetic, immunological, and environmental factors as well as gut microbiota dysbiosis. As a natural antioxidant with various pharmacological activities widely present in Oleaceae plants, oleuropein (OLE) exhibits anti-inflammatory, anti-tumor, ant...

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Main Authors: Rongxin Zang, Rui Zhou, Yaodong Li, Zhouliang Liu, Huihao Wu, Liping Lu, Hongwei Xu
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Foods
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Online Access:https://www.mdpi.com/2304-8158/14/11/1863
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author Rongxin Zang
Rui Zhou
Yaodong Li
Zhouliang Liu
Huihao Wu
Liping Lu
Hongwei Xu
author_facet Rongxin Zang
Rui Zhou
Yaodong Li
Zhouliang Liu
Huihao Wu
Liping Lu
Hongwei Xu
author_sort Rongxin Zang
collection DOAJ
description The pathogenesis of ulcerative colitis (UC) involves genetic, immunological, and environmental factors as well as gut microbiota dysbiosis. As a natural antioxidant with various pharmacological activities widely present in Oleaceae plants, oleuropein (OLE) exhibits anti-inflammatory, anti-tumor, antiviral, hypoglycemic, and cardioprotective effects. It has been validated that OLE extracted from olive oil can ameliorate UC. However, it remains unclear if and how OLE modulates the gut microbiota in the alleviation of UC. Therefore, this study was conducted to explore the mechanisms for OLE to alleviate UC induced by dextran sulfate sodium (DSS), with the focus placed on its regulatory function in the gut microbiota. The results indicated that OLE mitigated DSS-induced UC by enhancing the intestinal barrier function, reshaping the gut microbiota, and modulating bile acid metabolism. The fecal microbiota transplantation (FMT) experiment results further confirmed that the protective effect of OLE against UC could be mediated by alterations in the gut microbiota and their metabolites induced by OLE. Additionally, OLE increased the abundance of <i>Lactobacillus</i> and certain bile acid metabolites in the colon, including hyodeoxycholic acid (HDCA). HDCA could upregulate the expression of ZO-1 and claudin-3, restoring intestinal barrier integrity. Simultaneously, HDCA could inhibit the activation of the nuclear factor kappa-B (NF-κB) signaling pathway in the colon and relieve colonic inflammation. Overall, it was corroborated that OLE alleviated DSS-induced UC by modulating the gut microbiota and altering bile acid metabolism.
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spelling doaj-art-cb6899d36ca04ad3a9634348779aae982025-08-20T02:23:05ZengMDPI AGFoods2304-81582025-05-011411186310.3390/foods14111863Oleuropein Regulates Bile Acid Metabolism via Modulating the Gut Microbiota, Thereby Alleviating DSS-Induced Ulcerative Colitis in MiceRongxin Zang0Rui Zhou1Yaodong Li2Zhouliang Liu3Huihao Wu4Liping Lu5Hongwei Xu6College of Life Science and Engineering, Northwest Minzu University, Lanzhou 730100, ChinaCollege of Life Science and Engineering, Northwest Minzu University, Lanzhou 730100, ChinaCollege of Life Science and Engineering, Northwest Minzu University, Lanzhou 730100, ChinaCollege of Life Science and Engineering, Northwest Minzu University, Lanzhou 730100, ChinaKey Laboratory of Biotechnology and Bioengineering of State Ethnic Affairs Commission, Northwest Minzu University, Lanzhou 730030, ChinaCollege of Life Science and Engineering, Northwest Minzu University, Lanzhou 730100, ChinaCollege of Life Science and Engineering, Northwest Minzu University, Lanzhou 730100, ChinaThe pathogenesis of ulcerative colitis (UC) involves genetic, immunological, and environmental factors as well as gut microbiota dysbiosis. As a natural antioxidant with various pharmacological activities widely present in Oleaceae plants, oleuropein (OLE) exhibits anti-inflammatory, anti-tumor, antiviral, hypoglycemic, and cardioprotective effects. It has been validated that OLE extracted from olive oil can ameliorate UC. However, it remains unclear if and how OLE modulates the gut microbiota in the alleviation of UC. Therefore, this study was conducted to explore the mechanisms for OLE to alleviate UC induced by dextran sulfate sodium (DSS), with the focus placed on its regulatory function in the gut microbiota. The results indicated that OLE mitigated DSS-induced UC by enhancing the intestinal barrier function, reshaping the gut microbiota, and modulating bile acid metabolism. The fecal microbiota transplantation (FMT) experiment results further confirmed that the protective effect of OLE against UC could be mediated by alterations in the gut microbiota and their metabolites induced by OLE. Additionally, OLE increased the abundance of <i>Lactobacillus</i> and certain bile acid metabolites in the colon, including hyodeoxycholic acid (HDCA). HDCA could upregulate the expression of ZO-1 and claudin-3, restoring intestinal barrier integrity. Simultaneously, HDCA could inhibit the activation of the nuclear factor kappa-B (NF-κB) signaling pathway in the colon and relieve colonic inflammation. Overall, it was corroborated that OLE alleviated DSS-induced UC by modulating the gut microbiota and altering bile acid metabolism.https://www.mdpi.com/2304-8158/14/11/1863oleuropeinulcerative colitisnuclear factor kappa-B
spellingShingle Rongxin Zang
Rui Zhou
Yaodong Li
Zhouliang Liu
Huihao Wu
Liping Lu
Hongwei Xu
Oleuropein Regulates Bile Acid Metabolism via Modulating the Gut Microbiota, Thereby Alleviating DSS-Induced Ulcerative Colitis in Mice
Foods
oleuropein
ulcerative colitis
nuclear factor kappa-B
title Oleuropein Regulates Bile Acid Metabolism via Modulating the Gut Microbiota, Thereby Alleviating DSS-Induced Ulcerative Colitis in Mice
title_full Oleuropein Regulates Bile Acid Metabolism via Modulating the Gut Microbiota, Thereby Alleviating DSS-Induced Ulcerative Colitis in Mice
title_fullStr Oleuropein Regulates Bile Acid Metabolism via Modulating the Gut Microbiota, Thereby Alleviating DSS-Induced Ulcerative Colitis in Mice
title_full_unstemmed Oleuropein Regulates Bile Acid Metabolism via Modulating the Gut Microbiota, Thereby Alleviating DSS-Induced Ulcerative Colitis in Mice
title_short Oleuropein Regulates Bile Acid Metabolism via Modulating the Gut Microbiota, Thereby Alleviating DSS-Induced Ulcerative Colitis in Mice
title_sort oleuropein regulates bile acid metabolism via modulating the gut microbiota thereby alleviating dss induced ulcerative colitis in mice
topic oleuropein
ulcerative colitis
nuclear factor kappa-B
url https://www.mdpi.com/2304-8158/14/11/1863
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