BACKGROUND: Patients with ulcerative colitis (UC) exhibit abnormal amino acid (AA) metabolism. Taste receptors play a crucial role in the detection of intestinal AAs. Nevertheless, it remains unclear whether UC patients exhibit abnormal expression of these receptors in the colon. METHODS: An observational, multicenter study was conducted involving adult patients with active UC and healthy controls (HCs), recruited from July 2023 to March 2024. Fresh feces and rectosigmoid mucosal tissues were obtained from each participant. The concentrations of fecal AAs and the expression of taste receptors, including calcium-sensing receptor (CaSR), G protein-coupled receptor family C group 6 member A (GPRC6A), taste receptor type 1 member 1 (T1R1), and metabotropic glutamate receptor 4 (mGLuR4), in the colon were measured. Additionally, the correlation between colonic mucosal taste receptors and clinical characteristics was evaluated. RESULTS: Except for GPRC6A, the expression levels of CaSR, mGLuR4, and T1R1 in the colonic mucosa of UC patients were significantly elevated compared to HC. The expression of CaSR was negatively correlated with C-reactive protein and erythrocyte sedimentation rate (ESR). T1R1 expression positively correlated with defecation frequency and an Improved Mayo Endoscopic Score. The total and subtype concentrations of fecal AAs were elevated in UC patients and demonstrated a negative correlation with ESR and fecal calprotectin. CONCLUSIONS: The increased levels of taste receptors and fecal AAs in the colon of UC patients suggest an abnormal nutrient-sensing mechanism, potentially playing a crucial role in the development of the disease.