Recently, using a conditional genetic strategy to delete the enzyme PAPS Synthase 2 (PAPSS2) in gut epithelium, which promotes donor synthesis, it was demonstrated that sulfation defects in epithelial cells led to enhanced sensitivity to colitis and lumen-to-systemic spread of the colon microbiota,96 suggesting a more generalized tolerance strategy of sulfation toward the microbiota. This evidence concerns the gene PAPSS2 and colitis.