{Reference Type}: Journal Article
{Title}: Metabolomics study reveals increased deoxycholic acid contributes to deoxynivalenol-mediated intestinal barrier injury.
{Author}: He X;Zhou HX;Fu X;Ni KD;Lin AZ;Zhang LT;Yin HH;Jiang Q;Zhou X;Meng YW;Liu JY;
{Journal}: Life Sci
{Volume}: 336
{Issue}: 0
{Year}: 2024 Jan 1
{Factor}: 6.78
{DOI}: 10.1016/j.lfs.2023.122302
{Abstract}: <B>OBJECTIVE: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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-γ, 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-γ, 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).<BR><B>CONCLUSIONS: </B>DON-mediated increase in DCA contributes to DON-caused intestinal injury. DCA may be a potential therapeutic target for DON enterotoxicity.