Crocetin Prolongs Recovery Period of DSS-Induced Colitis via Altering Intestinal Microbiome and Increasing Intestinal Permeability

Crocetin is one of the major active constituents of saffron (<i>Crocus sativus</i> L.) which has a reputation for facilitating blood circulation and dispersing blood stasis in traditional Chinese medicine. However, there is little evidence showing the relationship between crocetin intake...

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Main Authors: Peishi Feng, Qiaoqiao Li, Ling Liu, Siyu Wang, Zhipeng Wu, Yi Tao, Pan Huang, Ping Wang
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/7/3832
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author Peishi Feng
Qiaoqiao Li
Ling Liu
Siyu Wang
Zhipeng Wu
Yi Tao
Pan Huang
Ping Wang
author_facet Peishi Feng
Qiaoqiao Li
Ling Liu
Siyu Wang
Zhipeng Wu
Yi Tao
Pan Huang
Ping Wang
author_sort Peishi Feng
collection DOAJ
description Crocetin is one of the major active constituents of saffron (<i>Crocus sativus</i> L.) which has a reputation for facilitating blood circulation and dispersing blood stasis in traditional Chinese medicine. However, there is little evidence showing the relationship between crocetin intake and the risk of gastrointestinal diseases such as colitis. In order to investigate the effect of crocetin on the regulation of intestinal barrier function and intestinal microbiota composition, mice were treated with crocetin after 3% dextran sulfate sodium (DSS) administration for one week. We found that crocetin intake at 10 mg/kg aggravated colitis in mice, showing increased weight loss and more serious histological abnormalities compared with the DSS group. The 16s rDNA sequencing analysis of the feces samples showed that mice treated with 10 mg/kg crocetin had lower species diversity and richness than those treated with DSS. At the genus level, a higher abundance of <i>Akkermansia</i> and <i>Mediterraneibacter</i>, and a lower abundance of <i>Muribaculaceae</i>, <i>Dubosiella</i>, <i>Paramuribaculum</i>, <i>Parasutterella</i>, <i>Allobaculum</i>, <i>Duncaniella</i>, <i>Candidatus Stoquefichus</i>, and <i>Coriobacteriaceae UCG-002</i> were observed in the crocetin group. Untargeted metabolomic analyses revealed that crocetin reduced the levels of primary and secondary bile acids such as 12-ketodeoxycholic acid, 7-ketodeoxycholic acid, 3-sulfodeoxycholic acid, 6-ethylchenodeoxycholic acid, chenodeoxycholate, glycochenodeoxycholate-7-sulfate, glycocholate, and sulfolithocholic acid in the colon. In conclusion, crocetin intake disturbed intestinal homeostasis and prolonged recovery of colitis by promoting inflammation and altering gut microbiota composition and its metabolic products in mice. Our findings suggest that patients with gastrointestinal diseases such as inflammatory bowel disease should use crocetin with caution.
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spelling doaj.art-0413aa339acc4ba3bfe163f89c9fc8d02023-11-30T23:22:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01237383210.3390/ijms23073832Crocetin Prolongs Recovery Period of DSS-Induced Colitis via Altering Intestinal Microbiome and Increasing Intestinal PermeabilityPeishi Feng0Qiaoqiao Li1Ling Liu2Siyu Wang3Zhipeng Wu4Yi Tao5Pan Huang6Ping Wang7College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, ChinaSchool of Medicine, Jiangsu University, Zhenjiang 212013, ChinaSchool of Medicine, Jiangsu University, Zhenjiang 212013, ChinaCollege of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, ChinaSchool of Medicine, Jiangsu University, Zhenjiang 212013, ChinaCollege of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, ChinaCrocetin is one of the major active constituents of saffron (<i>Crocus sativus</i> L.) which has a reputation for facilitating blood circulation and dispersing blood stasis in traditional Chinese medicine. However, there is little evidence showing the relationship between crocetin intake and the risk of gastrointestinal diseases such as colitis. In order to investigate the effect of crocetin on the regulation of intestinal barrier function and intestinal microbiota composition, mice were treated with crocetin after 3% dextran sulfate sodium (DSS) administration for one week. We found that crocetin intake at 10 mg/kg aggravated colitis in mice, showing increased weight loss and more serious histological abnormalities compared with the DSS group. The 16s rDNA sequencing analysis of the feces samples showed that mice treated with 10 mg/kg crocetin had lower species diversity and richness than those treated with DSS. At the genus level, a higher abundance of <i>Akkermansia</i> and <i>Mediterraneibacter</i>, and a lower abundance of <i>Muribaculaceae</i>, <i>Dubosiella</i>, <i>Paramuribaculum</i>, <i>Parasutterella</i>, <i>Allobaculum</i>, <i>Duncaniella</i>, <i>Candidatus Stoquefichus</i>, and <i>Coriobacteriaceae UCG-002</i> were observed in the crocetin group. Untargeted metabolomic analyses revealed that crocetin reduced the levels of primary and secondary bile acids such as 12-ketodeoxycholic acid, 7-ketodeoxycholic acid, 3-sulfodeoxycholic acid, 6-ethylchenodeoxycholic acid, chenodeoxycholate, glycochenodeoxycholate-7-sulfate, glycocholate, and sulfolithocholic acid in the colon. In conclusion, crocetin intake disturbed intestinal homeostasis and prolonged recovery of colitis by promoting inflammation and altering gut microbiota composition and its metabolic products in mice. Our findings suggest that patients with gastrointestinal diseases such as inflammatory bowel disease should use crocetin with caution.https://www.mdpi.com/1422-0067/23/7/3832crocetingut microbiotaulcerative colitisintestinal metabolitesinflammatory bowel disease
spellingShingle Peishi Feng
Qiaoqiao Li
Ling Liu
Siyu Wang
Zhipeng Wu
Yi Tao
Pan Huang
Ping Wang
Crocetin Prolongs Recovery Period of DSS-Induced Colitis via Altering Intestinal Microbiome and Increasing Intestinal Permeability
International Journal of Molecular Sciences
crocetin
gut microbiota
ulcerative colitis
intestinal metabolites
inflammatory bowel disease
title Crocetin Prolongs Recovery Period of DSS-Induced Colitis via Altering Intestinal Microbiome and Increasing Intestinal Permeability
title_full Crocetin Prolongs Recovery Period of DSS-Induced Colitis via Altering Intestinal Microbiome and Increasing Intestinal Permeability
title_fullStr Crocetin Prolongs Recovery Period of DSS-Induced Colitis via Altering Intestinal Microbiome and Increasing Intestinal Permeability
title_full_unstemmed Crocetin Prolongs Recovery Period of DSS-Induced Colitis via Altering Intestinal Microbiome and Increasing Intestinal Permeability
title_short Crocetin Prolongs Recovery Period of DSS-Induced Colitis via Altering Intestinal Microbiome and Increasing Intestinal Permeability
title_sort crocetin prolongs recovery period of dss induced colitis via altering intestinal microbiome and increasing intestinal permeability
topic crocetin
gut microbiota
ulcerative colitis
intestinal metabolites
inflammatory bowel disease
url https://www.mdpi.com/1422-0067/23/7/3832
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