Cargando…

Fucose promotes intestinal stem cell-mediated intestinal epithelial development through promoting Akkermansia-related propanoate metabolism

Intestinal stem cells (ISCs) are critical for the development and rapid turnover of intestinal epithelium. The regulatory effects of gut microbiota and their metabolites on ISCs stemness remain elusive. Fucose has been demonstrated to mediate host–microbe interactions in the intestine. However, the...

Descripción completa

Detalles Bibliográficos
Autores principales: Duan, Caihan, Wu, Junhao, Wang, Zhe, Tan, Chen, Hou, Lingzhi, Qian, Wei, Han, Chaoqun, Hou, Xiaohua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10334863/
https://www.ncbi.nlm.nih.gov/pubmed/37424378
http://dx.doi.org/10.1080/19490976.2023.2233149
_version_ 1785070937761120256
author Duan, Caihan
Wu, Junhao
Wang, Zhe
Tan, Chen
Hou, Lingzhi
Qian, Wei
Han, Chaoqun
Hou, Xiaohua
author_facet Duan, Caihan
Wu, Junhao
Wang, Zhe
Tan, Chen
Hou, Lingzhi
Qian, Wei
Han, Chaoqun
Hou, Xiaohua
author_sort Duan, Caihan
collection PubMed
description Intestinal stem cells (ISCs) are critical for the development and rapid turnover of intestinal epithelium. The regulatory effects of gut microbiota and their metabolites on ISCs stemness remain elusive. Fucose has been demonstrated to mediate host–microbe interactions in the intestine. However, the association between fucose, gut bacteria, and ISCs stemness remains unclear. To investigate the effects of fucose on ISCs-mediated intestinal epithelial cells (IECs) development, we administered fucose to 4-week-old mice for 4 weeks. ISCs stemness, IECs proliferation, and differentiation were examined. Variations in gut microbes and metabolism were detected using 16S rDNA sequencing and metabolomic analysis. Fucose was added to the bacterial culture medium to further study its effects on metabolism. Crypts were isolated from the mouse ileum for organoids culture in vitro to evaluate the effects of metabolites and the underlying mechanism. The results showed that fucose accelerated ISCs proliferation and secretory lineage differentiation in mice, whereas antibiotics eliminated these effects. The composition and functions of gut bacteria were altered by fucose treatment, while significant increases in Akkermansia and propanoate metabolism were noted. Propionic acid and propionate have been shown to promote organoid development. Fucose fermentation increases the production of propionic acid in Akkermansia muciniphila and enhances its ability to increase the stemness of ISCs. Moreover, ileal contents from fucose-treated mice promoted organoid development in a Gpr41/Gpr43-dependent manner. Fucose administration activates the Wnt signaling pathway in ISCs, and Wnt inhibitors suppress the effects of fucose. We conclude that fucose accelerates ISC-mediated intestinal epithelial development by promoting Akkermansia-related propanoate metabolism. These findings provide new insights into the promotion of gut homeostasis and the application potential of fucose as a prebiotic.
format Online
Article
Text
id pubmed-10334863
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Taylor & Francis
record_format MEDLINE/PubMed
spelling pubmed-103348632023-07-12 Fucose promotes intestinal stem cell-mediated intestinal epithelial development through promoting Akkermansia-related propanoate metabolism Duan, Caihan Wu, Junhao Wang, Zhe Tan, Chen Hou, Lingzhi Qian, Wei Han, Chaoqun Hou, Xiaohua Gut Microbes Research Paper Intestinal stem cells (ISCs) are critical for the development and rapid turnover of intestinal epithelium. The regulatory effects of gut microbiota and their metabolites on ISCs stemness remain elusive. Fucose has been demonstrated to mediate host–microbe interactions in the intestine. However, the association between fucose, gut bacteria, and ISCs stemness remains unclear. To investigate the effects of fucose on ISCs-mediated intestinal epithelial cells (IECs) development, we administered fucose to 4-week-old mice for 4 weeks. ISCs stemness, IECs proliferation, and differentiation were examined. Variations in gut microbes and metabolism were detected using 16S rDNA sequencing and metabolomic analysis. Fucose was added to the bacterial culture medium to further study its effects on metabolism. Crypts were isolated from the mouse ileum for organoids culture in vitro to evaluate the effects of metabolites and the underlying mechanism. The results showed that fucose accelerated ISCs proliferation and secretory lineage differentiation in mice, whereas antibiotics eliminated these effects. The composition and functions of gut bacteria were altered by fucose treatment, while significant increases in Akkermansia and propanoate metabolism were noted. Propionic acid and propionate have been shown to promote organoid development. Fucose fermentation increases the production of propionic acid in Akkermansia muciniphila and enhances its ability to increase the stemness of ISCs. Moreover, ileal contents from fucose-treated mice promoted organoid development in a Gpr41/Gpr43-dependent manner. Fucose administration activates the Wnt signaling pathway in ISCs, and Wnt inhibitors suppress the effects of fucose. We conclude that fucose accelerates ISC-mediated intestinal epithelial development by promoting Akkermansia-related propanoate metabolism. These findings provide new insights into the promotion of gut homeostasis and the application potential of fucose as a prebiotic. Taylor & Francis 2023-07-10 /pmc/articles/PMC10334863/ /pubmed/37424378 http://dx.doi.org/10.1080/19490976.2023.2233149 Text en © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Research Paper
Duan, Caihan
Wu, Junhao
Wang, Zhe
Tan, Chen
Hou, Lingzhi
Qian, Wei
Han, Chaoqun
Hou, Xiaohua
Fucose promotes intestinal stem cell-mediated intestinal epithelial development through promoting Akkermansia-related propanoate metabolism
title Fucose promotes intestinal stem cell-mediated intestinal epithelial development through promoting Akkermansia-related propanoate metabolism
title_full Fucose promotes intestinal stem cell-mediated intestinal epithelial development through promoting Akkermansia-related propanoate metabolism
title_fullStr Fucose promotes intestinal stem cell-mediated intestinal epithelial development through promoting Akkermansia-related propanoate metabolism
title_full_unstemmed Fucose promotes intestinal stem cell-mediated intestinal epithelial development through promoting Akkermansia-related propanoate metabolism
title_short Fucose promotes intestinal stem cell-mediated intestinal epithelial development through promoting Akkermansia-related propanoate metabolism
title_sort fucose promotes intestinal stem cell-mediated intestinal epithelial development through promoting akkermansia-related propanoate metabolism
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10334863/
https://www.ncbi.nlm.nih.gov/pubmed/37424378
http://dx.doi.org/10.1080/19490976.2023.2233149
work_keys_str_mv AT duancaihan fucosepromotesintestinalstemcellmediatedintestinalepithelialdevelopmentthroughpromotingakkermansiarelatedpropanoatemetabolism
AT wujunhao fucosepromotesintestinalstemcellmediatedintestinalepithelialdevelopmentthroughpromotingakkermansiarelatedpropanoatemetabolism
AT wangzhe fucosepromotesintestinalstemcellmediatedintestinalepithelialdevelopmentthroughpromotingakkermansiarelatedpropanoatemetabolism
AT tanchen fucosepromotesintestinalstemcellmediatedintestinalepithelialdevelopmentthroughpromotingakkermansiarelatedpropanoatemetabolism
AT houlingzhi fucosepromotesintestinalstemcellmediatedintestinalepithelialdevelopmentthroughpromotingakkermansiarelatedpropanoatemetabolism
AT qianwei fucosepromotesintestinalstemcellmediatedintestinalepithelialdevelopmentthroughpromotingakkermansiarelatedpropanoatemetabolism
AT hanchaoqun fucosepromotesintestinalstemcellmediatedintestinalepithelialdevelopmentthroughpromotingakkermansiarelatedpropanoatemetabolism
AT houxiaohua fucosepromotesintestinalstemcellmediatedintestinalepithelialdevelopmentthroughpromotingakkermansiarelatedpropanoatemetabolism