Fig. 1: Colitis mice and UC patients displayed elevated succinate levels. Treatment with a succinate receptor (SUCNR1) inhibitor in mice led to a decrease in inflammation.

A Volcano plots showing differential stool metabolites comparing colitis with healthy controls. B Volcano plots showing differential serum metabolites comparing colitis with healthy controls. C, D Volcano plots showing differential stool and serum metabolites comparing UC with healthy volunteers. E The hallmark metabolite, succinate, was significantly upregulated in both the stool and serum compartments of colitis mice and UC patients. The numbers represent various metabolites, with only succinate consistently elevated across all samples. F FACS data showing an increased frequency of SUCNR1⁺ IL-9⁺ CD4⁺ T cells in the lamina propria of Oxazolone-colitis mice compared to healthy mice. G Schematic illustrating the treatment regimen for SUCNR1 inhibition in oxazolone-induced colitis mice, using compound 7a. H Body weight recovery in oxazolone-induced colitis mice treated with compound 7a surpassed that of untreated mice. I Inflammatory lesion formation was significantly suppressed in oxazolone-induced colitis mice treated with compound 7a compared to untreated mice. J The expression levels of Th9-associated genes, including IL-9, Foxo1, IL-9R, and BATF, were quantified using qPCR from the MLNs of mice treated with compound 7a compared to untreated mice. K The expression level of SUCNR1, a surrogate indicator for succinate availability, was measured using qPCR in the MLNs of mice treated with compound 7a compared to untreated mice. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001 (Student’s t-test or one-way ANOVA).