Disruption of CerS6-mediated sphingolipid metabolism by FTO deficiency aggravates ulcerative colitis

BACKGROUND AND AIMS: A demethylases, in patients with ulcerative colitis (UC). METHODS: -ceramide. RESULTS: A modification and a decrease in mRNA stability of CerS6, the gene encoding ceramide synthetase, leading to the downregulation of CerS6 and the accumulation of S1P in IECs. Subsequentially, the secretion of S1P by IECs triggered proinflammatory macrophages to secrete serum amyloid A protein 1/3, ultimately inducing Th17 cell differentiation. In addition, through bioinformatic analysis and experimental validation, we identified UC patients with lower FTO expression might respond better to vedolizumab treatment. CONCLUSIONS: A-dependent mechanisms. Lower FTO expression in UC patients may enhance their response to vedolizumab treatment.