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• Plasma melatonin diagnoses early CKD patients with over 95% accuracy. • Plasma melatonin and tryptophan diagnose early CKD patients with 100% accuracy; • Plasma markers predict patients with early IgA nephropathy with over 85% accuracy. Chronic kidney disease (CKD) causes low quality of life and alarming morbidity and mortality. The crucial to retard CKD progression is to diagnose early for timely treatment. IgA nephropathy (IgAN) is a typical CKD and the most common glomerulonephritis. Both CKD and IgAN lack accurate and sensitive blood biomarkers for early diagnosis. Here we report the potential of plasma biomarkers for early diagnosis of CKD and IgAN. Plasma levels of metabolites derived from tryptophan were quantified with an LC-MS/MS-based metabolomics for two cohorts. Based on the predictive probability of each metabolite, multivariate models including logistic regression and random forest were used to establish the early diagnostic biomarkers for CKD and IgAN. The plasma melatonin diagnosed early CKD (stages Ⅰ−Ⅱ) with an accuracy exceeding 95%, and a panel of melatonin and tryptophan achieved a remarkable 100% accuracy in diagnosing early CKD. Furthermore, indole-3-lactic acid had an excellent ability to distinguish IgAN among CKD patients. Based on the CKD screening and IgAN diagnosis primarily contributed by melatonin and indole-3-lactic acid, early IgAN could be diagnosed with an accuracy of over 85%. This study provides promising plasma biomarkers for early diagnosis of CKD and IgAN. [ABSTRACT FROM AUTHOR]

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. 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. 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). DON-mediated increase in DCA contributes to DON-caused intestinal injury. DCA may be a potential therapeutic target for DON enterotoxicity. [Display omitted] • This study first demonstrated increased Deoxycholic acid (DCA) from Deoxynivalenol (DON) exposure using metabolomics. • DCA stimulates the expression of IFN-γ, related chemokines, and increase intestinal epithelial barrier permeability. • DCA contributes to DON-mediated gut barrier dysfunction. [ABSTRACT FROM AUTHOR]