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Vitamin A deficiency suppresses CEACAM1 to impair colonic epithelial barrier function via downregulating microbial-derived short-chain fatty acids

Vitamin A (VA) plays an essential role in modulating both the gut microbiota and gut barrier function. Short-chain fatty acids (SCFAs), as metabolites of the gut microbiota, protect the physiological intestinal barrier; however, they are compromised when VA is deficient. Thus, there is an urgent nee...

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Autores principales: Yan, Junyan, Xiao, Lu, Feng, Di, Chen, Baolin, Yang, Ting, Tong, Bei, Luo, Ruifang, Wang, Yuting, Chen, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Chongqing Medical University 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491915/
https://www.ncbi.nlm.nih.gov/pubmed/37692511
http://dx.doi.org/10.1016/j.gendis.2023.03.032
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author Yan, Junyan
Xiao, Lu
Feng, Di
Chen, Baolin
Yang, Ting
Tong, Bei
Luo, Ruifang
Wang, Yuting
Chen, Jie
author_facet Yan, Junyan
Xiao, Lu
Feng, Di
Chen, Baolin
Yang, Ting
Tong, Bei
Luo, Ruifang
Wang, Yuting
Chen, Jie
author_sort Yan, Junyan
collection PubMed
description Vitamin A (VA) plays an essential role in modulating both the gut microbiota and gut barrier function. Short-chain fatty acids (SCFAs), as metabolites of the gut microbiota, protect the physiological intestinal barrier; however, they are compromised when VA is deficient. Thus, there is an urgent need to understand how and which SCFAs modulate colonic epithelial barrier integrity in VA deficiency (VAD). Herein, compared with normal VA rats (VAN), at the beginning of pregnancy, we confirmed that the colonic desmosome junction was impaired in the VAD group, and the amounts of acetate, propionate, and butyrate declined because of the decreased abundance of SCFA-producing bacteria (Romboutsia, Collinsella, and Allobaculum). The differentially expressed genes correlated with the gut barrier and the histone deacetylase complex between the VAD and VAN groups were enriched by RNA sequencing. In the VAD group, the expression levels of colonic CEA cell adhesion molecule 1 (CEACAM1) were down-regulated, and the levels of histone deacetylase 1 (HDAC1) and HDAC3 were up-regulated. Intriguingly, the above changes in the VAD groups were rescued by VA supplementation in the early postnatal period. Further study indicated that in Caco-2 cells, butyrate treatment significantly repressed the enrichment of HDAC3 on the promoter of the CEACAM1 gene to induce its expression. Our findings support that butyrate intervention can alleviate the impairment of colonic barrier function caused by VAD, and timely postnatal VA intervention may reverse the damage caused by VAD on gut barrier integrity during pregnancy.
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spelling pubmed-104919152023-09-10 Vitamin A deficiency suppresses CEACAM1 to impair colonic epithelial barrier function via downregulating microbial-derived short-chain fatty acids Yan, Junyan Xiao, Lu Feng, Di Chen, Baolin Yang, Ting Tong, Bei Luo, Ruifang Wang, Yuting Chen, Jie Genes Dis Full Length Article Vitamin A (VA) plays an essential role in modulating both the gut microbiota and gut barrier function. Short-chain fatty acids (SCFAs), as metabolites of the gut microbiota, protect the physiological intestinal barrier; however, they are compromised when VA is deficient. Thus, there is an urgent need to understand how and which SCFAs modulate colonic epithelial barrier integrity in VA deficiency (VAD). Herein, compared with normal VA rats (VAN), at the beginning of pregnancy, we confirmed that the colonic desmosome junction was impaired in the VAD group, and the amounts of acetate, propionate, and butyrate declined because of the decreased abundance of SCFA-producing bacteria (Romboutsia, Collinsella, and Allobaculum). The differentially expressed genes correlated with the gut barrier and the histone deacetylase complex between the VAD and VAN groups were enriched by RNA sequencing. In the VAD group, the expression levels of colonic CEA cell adhesion molecule 1 (CEACAM1) were down-regulated, and the levels of histone deacetylase 1 (HDAC1) and HDAC3 were up-regulated. Intriguingly, the above changes in the VAD groups were rescued by VA supplementation in the early postnatal period. Further study indicated that in Caco-2 cells, butyrate treatment significantly repressed the enrichment of HDAC3 on the promoter of the CEACAM1 gene to induce its expression. Our findings support that butyrate intervention can alleviate the impairment of colonic barrier function caused by VAD, and timely postnatal VA intervention may reverse the damage caused by VAD on gut barrier integrity during pregnancy. Chongqing Medical University 2023-05-24 /pmc/articles/PMC10491915/ /pubmed/37692511 http://dx.doi.org/10.1016/j.gendis.2023.03.032 Text en © 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Full Length Article
Yan, Junyan
Xiao, Lu
Feng, Di
Chen, Baolin
Yang, Ting
Tong, Bei
Luo, Ruifang
Wang, Yuting
Chen, Jie
Vitamin A deficiency suppresses CEACAM1 to impair colonic epithelial barrier function via downregulating microbial-derived short-chain fatty acids
title Vitamin A deficiency suppresses CEACAM1 to impair colonic epithelial barrier function via downregulating microbial-derived short-chain fatty acids
title_full Vitamin A deficiency suppresses CEACAM1 to impair colonic epithelial barrier function via downregulating microbial-derived short-chain fatty acids
title_fullStr Vitamin A deficiency suppresses CEACAM1 to impair colonic epithelial barrier function via downregulating microbial-derived short-chain fatty acids
title_full_unstemmed Vitamin A deficiency suppresses CEACAM1 to impair colonic epithelial barrier function via downregulating microbial-derived short-chain fatty acids
title_short Vitamin A deficiency suppresses CEACAM1 to impair colonic epithelial barrier function via downregulating microbial-derived short-chain fatty acids
title_sort vitamin a deficiency suppresses ceacam1 to impair colonic epithelial barrier function via downregulating microbial-derived short-chain fatty acids
topic Full Length Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491915/
https://www.ncbi.nlm.nih.gov/pubmed/37692511
http://dx.doi.org/10.1016/j.gendis.2023.03.032
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