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

作者全名："Yan, Junyan; Xiao, Lu; Feng, Di; Chen, Baolin; Yang, Ting; Tong, Bei; Luo, Ruifang; Wang, Yuting; Chen, Jie"

作者地址："[Yan, Junyan; Xiao, Lu; Feng, Di; Chen, Baolin; Yang, Ting; Tong, Bei; Luo, Ruifang; Chen, Jie] Chongqing Med Univ, Children Nutr Res Ctr, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Child Nutr & Hlth,Childrens Hosp, Chongqing 401122, Peoples R China; [Xiao, Lu; Wang, Yuting] Chongqing Med Univ, Childrens Hosp, Dept Gastroenterol, Chongqing 401122, Peoples R China"

通信作者："Chen, J (通讯作者)，Chongqing Med Univ, Children Nutr Res Ctr, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Child Nutr & Hlth,Childrens Hosp, Chongqing 401122, Peoples R China.; Wang, YT (通讯作者)，Chongqing Med Univ, Childrens Hosp, Dept Gastroenterol, Chongqing 401122, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001073836300001

JCR分区：Q1

影响因子：6.9

年份：2024

卷号：11

期号：2

开始页：1066

结束页：1081

文献类型：Article

关键词：CEACAM1; Colonic epithelial barrier; HDAC3; Short-chain fatty acids; Vitamin A deficiency

摘要："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. 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/)."

基金机构：National Natural Science Foundation of China [31971089]; General Project of Chongqing Natural Science Foundation (China) [CSTB2022NSCQ-MSX0107]; Scientific Research Innovation Project for Postgraduates in Chongqing City (China) [CYS19198]

基金资助正文："This work was supported by grants from The National Natural Science Foundation of China (No. 31971089), the General Project of Chongqing Natural Science Foundation (China) (No. CSTB2022NSCQ-MSX0107), and the Scientific Research Innovation Project for Postgraduates in Chongqing City (China) (No. CYS19198)."