In the management of patients with inflammatory bowel diseases (IBD), there is a need to identify druggable biological pathways to improve mucosal repair and efficacy of TNF alpha biologics. Based on the VIVA transgenic model of Vnn1 overexpression on intestinal cells, the inventors show that the epithelial pantetheinase Vnn1 has a dual effect on colon: (1) its enzymatic products, cysteamine and pantothenic acid (vitamin B5) enhance coenzyme A regeneration and colon fitness through metabolic rewiring; (2) they favor microbiota-dependent accumulation of butyrate, previously shown to regulate mucosal energetics and to be reduced in IBD patients. Upon dextran sodium sulfate (DSS)-induced colitis, Vnn1 exerts a cytoprotective role on colonocytes and reinforces the mucosal barrier. Remarkably, this global pro-healing phenotype is recapitulated by treating control mice with the substrate (pantethine) or the products of pantetheinase activity prior to exposure to DSS. Therefore, enhancement of vitamin B5-driven metabolism should improve mucosal healing and maintain colon fitness and might enhance the efficacy of anti-inflammatory anti-TNF alpha therapy.