Metabolomics study reveals increased deoxycholic acid contributes to deoxynivalenol-mediated intestinal barrier injury

作者全名："He, Xin; Zhou, Hong-Xu; Fu, Xian; Ni, Kai-Di; Lin, Ai-Zhi; Zhang, Ling-Tong; Yin, Hou-Hua; Jiang, Qing; Zhou, Xue; Meng, Yi-Wen; Liu, Jun-Yan"

作者地址："[Liu, Jun-Yan] Chongqing Med Univ, Affiliated Hosp 2, Inst Life Sci, CNTTI, Chongqing 400016, Peoples R China; [Liu, Jun-Yan] Chongqing Med Univ, Affiliated Hosp 2, Anesthesia Dept, Chongqing 400016, Peoples R China; Minist Educ, Basic Med Res & Innovat Ctr Novel Target & Therape, Chongqing 400016, Peoples R China"

通信作者："Liu, JY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Inst Life Sci, CNTTI, Chongqing 400016, Peoples R China.; Liu, JY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Anesthesia Dept, Chongqing 400016, Peoples R China."

来源：LIFE SCIENCES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001127048200001

JCR分区：Q1

影响因子：6.1

年份：2024

卷号：336

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Bile acids; Chemokines; Deoxynivalenol; Deoxycholic acid; Intestinal barrier; Metabolomics

摘要："Aims: Deoxynivalenol (DON), namely vomitoxin, is one of the most prevalent fungal toxins in cereal crops worldwide. However, the underlying toxic mechanisms of DON remain largely unknown. Main methods: DON exposure-caused changes in the murine plasma metabolome and gut microbiome were investigated by an LC-MS/MS-based nontargeted metabolomics approach and sequencing of 16S rRNA in fecal samples, respectively. Cellular models were then used to validate the findings from the metabolomics study.Key findings: DON exposure increased intestinal barrier permeability evidenced by its-mediated decrease in colonic Claudin 5 and E-cadherin, as well as increases in colonic Ifn-gamma, Cxcl9, Cxcl10, and Cxcr3. Furthermore, DON exposure resulted in a significant increase in murine plasma levels of deoxycholic acid (DCA). Also, DON exposure led to gut microbiota dysbiosis, which was associated with DON exposure-caused increase in plasma DCA. In addition, we found not only DON but also DCA dose-dependently caused a significant increase in the levels of IFN-gamma, CXCL9, CXCL10, and/or CXCR3, as well as a significant decrease in the expression levels of Claudin 5 and/or E-cadherin in the human colonic epithelial cells (NCM460).Significance: DON-mediated increase in DCA contributes to DON-caused intestinal injury. DCA may be a potential therapeutic target for DON enterotoxicity."

基金机构：Chongqing Municipal Natural Science Foundation-Education Commission Joint Fund for Innovation and Development Key Project [CSTB2022NSCQ-LZX0027]; Chongqing Medical University

基金资助正文：<B>Acknowledgments</B> This study was co-supported by the Chongqing Municipal Natural Science Foundation-Education Commission Joint Fund for Innovation and Development Key Project (CSTB2022NSCQ-LZX0027) and a startup grant from Chongqing Medical University.